Nanoparticles for sequential exposure to low intensity sound waves for medical or cosmetic applications

Abstract

The invention relates to nanoparticles for sequential exposure to low intensity sound waves for medical or cosmetic applications, in particular to nanoparticles for use in sound wave medical treatment of a body part of an individual, wherein the nanoparticles are applied to the body part of the individual and the sound waves are applied to the body part, wherein: the sound waves are applied sequentially to the body part, and / or the nanoparticles are magnetosomes.

Description

[0001] This application is a divisional application of Chinese patent application No. 201880076134.8, filed on November 29, 2018, entitled "Nanoparticles sequentially exposed to low-intensity sound waves for medical or cosmetic applications". Technical Field

[0002] This invention relates to nanoparticles that are sequentially exposed to low-intensity sound waves for medical treatment. Background Technology

[0003] Currently, diseases such as cancer, such as prostate cancer, can be treated with ultrasound, typically using high-intensity focused ultrasound (HIFU). However, this treatment method has some drawbacks. To achieve the desired effect, HIFU usually requires heating cancerous tissue at relatively high temperatures, which can damage healthy tissue. Using HIFU typically requires heating the tumor at several locations to eradicate it. To overcome these drawbacks, low-intensity ultrasound (LIU) can be used instead of HIFU. In this invention, we propose a method for effectively using low-intensity ultrasound (LIU) in medical treatment. It is based on using nanoparticles located at the pathological site and sequentially exposing them to low-intensity sound waves (Nature Reviews Cancer, V.5, P.321 (2005)). Summary of the Invention

[0004] The present invention also relates to nanoparticles for acoustic medical therapy on individual body parts, wherein the nanoparticles are applied to the individual body parts and acoustic waves are applied to the body parts, wherein:

[0005] The sound waves were applied sequentially to different parts of the body, and / or

[0006] Nanoparticles are magnetic bodies.

[0007] The present invention also relates to nanoparticles for radiomedical therapy of individual body parts, wherein the nanoparticles are applied to the individual body parts and the radiation is applied to the body parts, wherein:

[0008] - Radiation is applied sequentially to parts of the body, and / or

[0009] - Nanoparticles are magnetic bodies.

[0010] The present invention also relates to nanoparticles for radiation or sound wave medical treatment of individual body parts, wherein the nanoparticles are applied to the individual body parts and radiation or sound waves are applied to the body parts, wherein:

[0011] - Radiation or sound waves are applied sequentially to parts of the body, and / or

[0012] Nanoparticles are synthesized by living organisms and are mainly concentrated inside or outside the organism.

[0013] The present invention also relates to magnetic bobbins for use in acoustic or radiological medical treatments of an individual's body parts, wherein the magnetic bobbins are applied to the individual's body parts and the body parts are exposed to acoustic waves or radiation. In some cases, the magnetic bobbins are applied to the individual's body parts and the body parts are exposed to acoustic waves or radiation.

[0014] The present invention also relates to nanoparticles for acoustic or radiological medical treatment of individual body parts, wherein the nanoparticles are applied to the individual body parts, and acoustic waves or radiation are preferably applied sequentially to the nanoparticles and / or the body parts. The present invention also relates to a method for treating an individual body part, comprising applying an effective dose of nanoparticles to the body part, and preferably sequentially applying an effective dose of acoustic waves or radiation to the body part, wherein the nanoparticles are preferably magnetosomes.

[0015] In some cases, nanoparticles can be applied to parts of an individual's body, and the body parts can preferably be exposed to sound waves or radiation in sequence.

[0016] In some cases, it can be said that sound waves are applied to nanoparticles or body parts, or that nanoparticles or body parts are exposed to sound waves or radiation.

[0017] In one embodiment of the present invention, nanoparticles refer to more than 1, 10, 10 2 10 3 10 5 10 10 Or 10 50 Nanoparticles or the assembly of nanoparticles.

[0018] In another embodiment of the invention, the nanoparticles are specified to be less than 10. 100 10 50 10 20 10 10 10 5 10 3 10 2 50, 10, 5, 2 or 1 nanoparticles or the assembly of nanoparticles.

[0019] In one embodiment of the invention, the nanoparticle region is: i) a region comprising a body portion of the nanoparticle, ii) a volume occupied by the nanoparticle within the body portion, or iii) a volume occupied by the nanoparticle outside the body portion.

[0020] This invention relates to nanoparticles for use according to the invention, wherein the sound waves have at least one of the following properties:

[0021] i1) the power or power density thereof is lower than 1000 watts (W),

[0022] i2) the power or power density thereof is lower than 1000 watts per centimeter, watts per square centimeter, or watts per cubic centimeter,

[0023] i3) the power or power density thereof is lower than 1000 watts per centimeter of body part, watts per square centimeter of body part, or watts per cubic centimeter of body part,

[0024] i4) the power or power density thereof is lower than 1000 watts per centimeter of transducer, watts per square centimeter of transducer, or watts per cubic centimeter of transducer

[0025] i5) the power or power density thereof is lower than 1000 watts per gram of nanoparticles,

[0026] ii1) the energy or energy density thereof is lower than 10 5 watt-seconds,

[0027] ii2) the energy or energy density thereof is lower than 10 5 watt-seconds per centimeter, watt-seconds per square centimeter, or watt-seconds per cubic centimeter,

[0028] ii3) the energy or energy density thereof is lower than 10 5 watt-seconds per centimeter of body part, watt-seconds per square centimeter of body part, or watt-seconds per cubic centimeter of body part,

[0029] ii4) the energy or energy density thereof is lower than 10 5 watt-seconds per centimeter of transducer, watt-seconds per square centimeter of transducer, or watt-seconds per cubic centimeter of transducer,

[0030] ii5) the energy or energy density thereof is lower than 10 5 joules (J),

[0031] ii6) the energy or energy density thereof is lower than 10 5 joules per centimeter, joules per square centimeter, or joules per cubic centimeter,

[0032] ii7) the energy or energy density thereof is lower than 10 5 joules per centimeter of body part, joules per square centimeter of body part, or joules per cubic centimeter of body part,

[0033] ii8) the energy or energy density thereof is lower than 10 5 joules per centimeter of transducer, joules per square centimeter of transducer, or joules per cubic centimeter of transducer,

[0034] ii9) the energy or energy density thereof is lower than 105 joules per gram of nanoparticles,

[0035] iii) Its frequency is below 10 5 megahertz

[0036] iv) Its penetration depth into the body is greater than 10 -5 centimeter,

[0037] v) It is unfocused, and / or

[0038] vi) It is not focused ultrasound or high-intensity focused ultrasound.

[0039] In one embodiment of the invention, sound waves or radiation radiating body parts and / or nanoparticles and / or being applied to body parts or nanoparticles can mean that the sound waves or radiation cover, target, are present or located in the body parts or nanoparticles, or are present in at least 10% of the body parts or nanoparticles. -9 10 -7 10 -5 10 -3 10 -1 1, 5, 10, 25, 50, 75 or 80% of the body parts or nanoparticles, or at least 10%. -100 10 -50 10 -10 10 -9 10 -7 10 -5 10 -3 10 -1 1, 5, 10, 25, 50, 75, or 80% of the body parts or nanoparticles are exposed to sound waves or radiation. This percentage may represent the number or volume of nanoparticles or body parts exposed to sound waves or radiation divided by the total number or volume of nanoparticles or body parts. In some cases, sound waves or radiation may also cover, target, be present, be applied to, or be located outside the body parts or nanoparticles, preferably when the sound waves or radiation have sufficiently low power or energy to not cause toxicity.

[0040] In one embodiment of the invention, the excitation of nanoparticles by radiation or sound waves, or the irradiation of a body part or nanoparticles by sound waves or radiation, or the application of radiation or sound waves, preferably on the nanoparticles or body part, begins or occurs in less than 100%, 90%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 2%, 1%, or 0.1% of the body part. This percentage can be the ratio of the volume of radiation or sound waves applied thereon to the volume of the body part.

[0041] In one embodiment of the invention, when a body part or nanoparticle is irradiated or exposed to sound waves or radiation, the body part or nanoparticle receives or absorbs the energy or power of the sound waves or radiation. In some cases, the body part or nanoparticle receives or absorbs at least 10%. -9 10 -7 10 -5 10 -3 10 -1 1, 5, 10, 25, 50, 75, or 80% of the energy or power of the sound waves or radiation. This can be when the concentration of nanoparticles in the body part and / or the energy or power of the sound waves or radiation applied to the body part and / or nanoparticles is high. In some other cases, the body part or nanoparticles receive or absorb less than 80, 70, 50, 60, 10, 5, or 1% of the energy or power of the sound waves or radiation. This can be when the concentration of nanoparticles in the body part and / or the energy or power of the sound waves or radiation applied to the body part and / or nanoparticles is low. In some cases, this percentage is: i) the ratio of the energy of the sound waves or radiation absorbed or received by the body part to the energy of the sound waves or radiation applied to the body part or nanoparticles, or ii) the ratio between the power or energy of the sound waves or radiation absorbed or received by the body part or nanoparticles and the power or energy of the sound waves or radiation generated by the device generating the sound waves or radiation.

[0042] In this invention, a sound wave can be defined as: i) a mechanical wave, preferably causing interference or disturbance to the medium through which it passes, such as compression and / or expansion of the medium; ii) an elastic wave; iii) a wave that does not propagate or exist within a cavity; or iv) a wave that induces or is associated with the motion or vibration of matter, atoms, ions, matter, atoms, ions, or nanoparticles having non-zero mass or non-zero weight. Sound waves are generally not electromagnetic waves. However, in some cases, they can generate or produce electromagnetic waves, for example, if the moving / vibrating matter associated with the sound wave has a non-zero charge. An example of radiation generated by, associated with, or produced by, a sound wave could be acoustic radiation force. The term “sound wave” can refer to sound wave energy, sound wave power, sound wave intensity, or sound wave frequency. In some cases, sound wave intensity can have a similar meaning to sound wave power or sound wave energy. In other cases, sound wave power can have a similar meaning to sound wave energy. Sound waves can be absorbed, reflected, or transmitted by nanoparticles or body parts. Sound waves can have frequency, energy, power, or intensity, which can be specified as sound wave frequency, energy, power, or intensity, respectively. Sound waves can refer to values ​​greater than 1, 10, 10, etc. 2 10 3 10 5 10 10 Or 10 20Components of a sound wave. Sound wave energy can be expressed as sound wave power multiplied by the time the sound wave is applied. It can be expressed as power (e.g., watts) multiplied by time (e.g., seconds). Sound wave energy density can be expressed as sound wave energy per unit length, such as centimeters, or per unit surface area, such as square centimeters, or per unit volume, such as cubic centimeters. Sound wave power can be proportional to the sound wave energy per unit time. It can be expressed in power units (e.g., watts). Sound wave power density can be expressed as sound wave power per unit length (e.g., centimeters), per unit surface area (e.g., square centimeters), or per unit volume (e.g., cubic centimeters). Sound wave intensity can be proportional to the sound wave power per unit surface area, such as square centimeters. It can be expressed as power units (e.g., watts) divided by surface area units (e.g., square centimeters). In some cases, unit length, unit surface area, and unit volume can represent the length, surface area, and volume of nanoparticles, respectively.

[0043] In one embodiment of the invention, a sound wave is a wave that is associated with, or connected to, or induced, or generated, or originates from, or is caused by, or is attributed to, or triggers the motion, vibration, or oscillation of a substance or a collection of such substances, which has: i) in some cases greater than 10 -20 10 -10 10 -5 10 -3 10 -1 1, 2, 5, 10, 10 5 Or 10 7 ii) less than 10 grams or grams per cubic centimeter of body part or nanoparticles. 9 10 7 10 5 10 3 10 2 ,10,1,10 -2 10 -5 10 -7 10 -9 10 -20 Or 10 -50 The number of grams or grams per cubic centimeter of body part or nanoparticles, iii) a number between 0 and 10 20 10 -20 and 10 20 10 -10 and 10 10 or between 10 -10 and 10 grams or grams per cubic centimeter of body part or nanoparticles iii) in some cases positive charge, iv) in some other cases negative charge, and / or v) in some other cases neutral charge.

[0044] In one embodiment of the present invention, the substance is nanoparticles.

[0045] In some cases, sound waves can be attributed to values ​​greater than 2, 5, 10, 10. 5 10 10 Or 10 20 The movement or time-varying behavior of nanoparticles is preferably less than 10. 10 10 5 10 3 , 10, 5, 2, 1, 10 -2 Or 10 -5 The concentration of nanoparticles is preferably greater than 1.1, 2, 5, 10, or 10 minutes. 5 10 10 Or 10 20 Factors in which the movement or concentration of nanoparticles preferably occurs in body parts.

[0046] In one embodiment of the invention, the motion, vibration, or oscillation of matter is periodic, or periodically repetitive. In this case, the motion, vibration, or oscillation of matter may preferably be repeated more than 2, 5, 10, or 10 times. 3 10 6 Or 10 9 The repetition preferably refers to at least one property related to the motion, vibration or oscillation of a substance that can be repeated, wherein the property can be the velocity or velocity change of the substance with respect to time or space, displacement or displacement change with respect to time or space, or acceleration or acceleration change with respect to time or space.

[0047] In this invention, sound waves can be defined as infrasound, sound, ultrasound, or giant sound waves.

[0048] In this invention, the sound wave is preferably ultrasound, and preferably has: i) including 10 2 Between 100 MHz and 100 MHz, in 10 -1 and 10 MHz or between 1 and 5 MHz, and / or ii) at 10 MHz -2 and 10 2 Between 10 per square centimeter of tile -1 The power ranges between 10 watts per square meter and 1 to 5 watts per square centimeter.

[0049] Preferably, infrasound can be defined as low-frequency sound waves. In some cases, the frequency of infrasound can be below 2, 20, 200, 2000, or 10. 5 Hertz. In some other cases, the frequency of infrasound can be greater than 10. -100 10 -50 Or 10-10 Hertz. Ideally, the frequency of infrasound should be below 20 Hz.

[0050] Preferably, sound can be defined as the frequency of sound: i) in some cases greater than 2.10. -3 ii) In some other cases, the frequency is below 2,20,200 or 2.10 Hz. 5 kilohertz. Most preferably, the sound has a frequency between 16 Hz and 16 kilohertz.

[0051] Preferably, ultrasound can be defined as the frequency of sound: i) greater than 2.10 in some cases. -3 ii) in some other cases, the frequency is below 0.1, 1, 10, or 10 kHz. 5 Giertz. Most preferably, the ultrasound has a frequency between 16 kHz and 10 MHz.

[0052] Preferably, megasonic waves can be defined as high-frequency sound waves. In some cases, the frequency of megasonic waves may be greater than 10. -10 10 -3 10 -2 10 -1 1 or 10 gigahertz. In some other cases, the frequency of ultrasound may be lower than 10. 1000 10 100 10 10 Or 10 5 gigahertz. Most preferably, the giant sound wave has a frequency greater than 10 megahertz.

[0053] In some cases, sound waves, infrasound, sound, ultrasound, or giant acoustic waves can be waves, preferably longitudinal waves, and their frequencies are preferably included in the range of 10. -100 and 10 100 Between Hertz.

[0054] In some cases, when a sound wave passes through a propagation medium and its frequency increases as it passes through that medium, the frequency of the sound wave can reach a relatively high value.

[0055] In some other cases, the frequency of a sound wave can reach a lower value when it passes through a propagation medium and its frequency decreases as it passes through that medium.

[0056] In one embodiment of the invention, the frequency of the ultrasonic wave is greater than that of sound or the frequency of the giant acoustic wave is greater than that of the ultrasonic wave, preferably by a factor of: i) greater than 1.001, 1.1, 2, 5, 10 or 10 in some cases. 3 ii) In some other cases, it is less than 0 50 10 20 1010 10 5 10 3 , 10, 5 or 2, or iii) in some other cases at 1.00001 and 10 50 between.

[0057] According to the present invention, the form of radiation can be a wave, such as an electromagnetic wave, a sound or acoustic wave, or a particle wave. The particle may have: i) in some cases, weight or mass; ii) in some other cases, no weight or mass; iii) in some cases, be mobile; or iv) in some other cases, not be mobile.

[0058] In another embodiment of the invention, radiation is a wave that is associated with, linked to, induced, generated, originated from, caused by, attributed to, or induced the motion, vibration, or oscillation of a substance or a collection of such substances, which has: i) zero mass or ii) a mass less than the mass of the substance associated with, linked to, induced by, generated by, or attributed to the sound wave, exceeding 1.111, 1.5, 2, 5, 10, 10 3 Or 10 5 times.

[0059] According to the present invention, the form of radiation may be electromagnetic radiation.

[0060] According to the present invention, radiation can be acoustic radiation force, radiation force or radiation pressure in some cases.

[0061] According to the present invention, the radiation can preferably be sound waves irradiating a part of the body.

[0062] Preferably, the radiation source is selected from: i) magnetic field or electric field, ii) laser, iii) light generated by lamp, iv) light emitted at a single wavelength, v) light emitted at multiple wavelengths, vi) ionizing radiation, vii) microwave, viiii) radio frequency and ix) sound wave.

[0063] In some cases, radiation can be selected from: alpha, beta, gamma, X-rays, neutrons, protons, electrons, ions, neutrinos, muons, mesons, and photons, or radiation.

[0064] Preferably, the radiation can also be selected from sound waves, infrasound, sound, ultrasound, and giant sound waves in some cases.

[0065] Preferably, the radiation generates or causes or induces a magnetic or electromagnetic field. In some cases, the intensity of the magnetic or electromagnetic field is greater than 1 μT, 10 μT, 100 μT, 1 mT, 10 mT, 100 mT, 1 T, 5 T, 10 T, or 100 T. In some other cases, the intensity of the magnetic or electromagnetic field is less than 10 T.20 10 5 10 2 ,10,1,10 -1 10 -3 Or 10 -9 T.

[0066] In some cases, the radiation according to the invention can have a value greater than 10. -10 10 -5 10 -3 , 0.01, 0.1, 1, 10, 10 2 10 3 10 5 Or 10 7 Gray, or Gray per cubic centimeter of body portion, or Gray per gram of body portion, or Gray per cubic centimeter of nanoparticles, or Gray per gram of nanoparticles.

[0067] In some other cases, the radiation according to the invention can have a value of less than 10. 100 10 50 10 10 10 5 10 2 ,10,1,10 -3 Or 10 -5 Gray or Gray per cubic centimeter of body portion or Gray per gram of body portion or Gray per cubic centimeter of nanoparticles or Gray per gram of nanoparticles.

[0068] In another embodiment of the invention, the sound wave is not at least one type of radiation selected from the group consisting of: i) electromagnetic radiation, ii) magnetic field, iii) electric field, iv) alternating electric or magnetic field, v) laser or laser line, vi) light emitted by a lamp or lamp, vii) light emitted at a single wavelength, viii) light emitted at multiple wavelengths, ix) ionizing radiation, x) microwave, xi) radio frequency, xii) photon, and xiii) α, β, γ, X-rays, neutron, proton, electron, ion, neutrino, g example, meson, light particle or radiation, and xiv) radiation of particles, matter or photons originating from atoms or molecules.

[0069] In some cases, sound waves can be sound radiation or be replaced by sound radiation.

[0070] In some cases, sound waves or radiation can be or represent values ​​greater than 1, 5, 10, 10. 3 10 5 10 10 10 20 Or 10 50 A component in the form of sound waves or radiation. In other cases, sound waves or radiation can be or represent less than 10. 100 1050 10 20 10 10 10 5 10 2 5 or 2 components in the form of sound waves or radiation.

[0071] In this invention, radiation or sound waves can be generated by a device that produces radiation or sound waves, preferably before, during, or after the radiation or sound waves have reached, covered, or targeted the body part or nanoparticles. In some cases, the device or apparatus is different from nanoparticles and is preferably man-made.

[0072] In some cases, the device that generates sound waves is or includes a transducer, which preferably converts electrical signals into sound waves.

[0073] In this invention, radiation or sound waves can, in some cases, be generated by nanoparticles. In this case, the radiation or sound waves may be due to changes in the structure of the nanoparticles, preferably before, after, or during the application of the nanoparticles to a body part or individual. For example, the nanoparticles may be organized in a chain-like structure before application to an individual, and then, after application, gradually degrade via, for example, lysosomes, resulting in changes in the distance between the nanoparticles, preferably an increase, and thus causing changes in the interactions between the nanoparticles, which can generate sound waves or radiation.

[0074] In one embodiment of the invention, the intensity, power, energy, and frequency of the sound wave or radiation are the intensity or frequency of the sound wave generated by the device that generates the sound wave or radiation, or by the transducer. It can be the intensity, power, energy, or frequency of the sound wave or radiation measured immediately after it leaves the device that generates the sound wave or radiation or leaves the transducer. Alternatively, it can be the intensity, power, energy, or frequency of the sound wave or radiation measured after it leaves the device that generates the sound wave or radiation or leaves the transducer and has propagated through another medium (liquid, gas, solid), such as a body part.

[0075] In some cases, the device for detecting sound waves can be a sound wave sensor, preferably including a transducer, which preferably converts sound wave power or energy into an electrical signal.

[0076] In some cases, the intensity or power of a sound wave or radiation cannot be detected because it is too small or cannot be detected by available sound wave or radiation detectors. In such cases, the presence of the sound wave or radiation can be revealed by changes in the motion, oscillation, size, organization, composition, or charge of the material that generates the sound wave (e.g., nanoparticles).

[0077] The present invention also relates to nanoparticles used according to the invention, wherein the intensity, power, or power density of the sound wave or radiation is less than:

[0078] 10 100 10 50 10 20 10 10 10 9 10 6 10 5 10 3 10 2 100, 50, 10, 5, 3, 1, 10 -1 10 -2 10 -3 10 -5 Or 10 -7 Watt

[0079] 10 100 10 50 10 20 10 10 10 9 10 6 10 5 10 3 10 2 100, 50, 10, 5, 3, 1, 10 -1 10 -2 10 -3 10 -5 Or 10 -7 Tiles per centimeter, tiles per square centimeter, or tiles per cubic centimeter.

[0080] 10 100 10 50 10 20 10 10 10 9 10 6 10 5 10 3 10 2 100, 50, 10, 5, 3, 1, 10 -1 10 -2 10 -3 10 -5 Or 10 -7 Tiles per centimeter of body portion, tiles per square centimeter of body portion, or tiles per cubic centimeter of body portion.

[0081] 10 100 10 50 10 20 10 10 10 9 10 6 10 5 103 10 2 100, 50, 10, 5, 3, 1, 10 -1 10 -2 10 -3 10 -5 Or 10 -7 Watts per centimeter of transducer, Watts per square centimeter of transducer, or Watts per cubic centimeter of transducer, or

[0082] 10 100 10 50 10 20 10 10 10 9 10 6 10 5 10 3 10 2 100, 50, 10, 5, 3, 1, 10 -1 10 -2 10 -3 10 -5 Or 10 -7 Vaper per gram of nanoparticles.

[0083] In some cases, 1 cubic centimeter, 1 square centimeter, and 1 centimeter are respectively the body part of 1 cubic centimeter, 1 square centimeter, and 1 centimeter.

[0084] In other cases, 1 cubic centimeter, 1 square centimeter, and 1 centimeter can be a 1 cubic centimeter sensor, a 1 square centimeter sensor, and a 1 centimeter sensor, respectively.

[0085] In some cases, a transducer can represent the part of the transducer that generates sound waves.

[0086] In some other cases, 1 gram of nanoparticles can be 1 gram of nanoparticles exposed to sound waves or radiation, or 1 gram of nanoparticles subjected to sound waves.

[0087] This invention also relates to nanoparticles used according to the invention, wherein the intensity, power, or power density of the sound wave or radiation is higher than:

[0088] i) 10 -100 , 10 -50 , 10 -20 , 10 -10 , 10 -7 , 10 -5 , 10 -3 , 10 -2 , 10 -1 , 1, 5, 10, 10 2 103 , 10 5 , 10 7 Or 10 9 Watt

[0089] ii) 10 -100 , 10 -50 , 10 -20 , 10 -10 , 10 -7 , 10 -5 , 10 -3 , 10 -2 , 10 -1 , 1, 5, 10, 10 2 10 3 , 10 5 , 10 7 Or 10 9 Tiles per centimeter, tiles per square centimeter, or tiles per cubic centimeter.

[0090] iii) 10 -100 , 10 -50 , 10 -20 , 10 -10 , 10 -7 , 10 -5 , 10 -3 , 10 -2 , 10 -1 , 1, 5, 10,10 2 , 10 3 , 10 5 , 10 7 Or 10 9 Tiles per centimeter of body portion, tiles per square centimeter of body portion, or tiles per cubic centimeter of body portion.

[0091] iv) 10 -100 , 10 -50 , 10 -20 , 10 -10 , 10 -7 , 10 -5 , 10 -3 , 10 -2 , 10 -1 , 1, 5, 10, 10 2 10 3 , 10 5 , 10 7 Or 10 9 Watts per centimeter of transducer, Watts per square centimeter of transducer, or Watts per cubic centimeter of transducer.

[0092] v) 10 -100 , 10 -50 , 10 -20 , 10 -10 , 10 -7 , 10 -5 , 10 -3 , 10 -2 , 10 -1 , 1, 5, 10, 10 2 10 3 , 10 5 , 10 7 Or 10 9 Vaper per gram of nanoparticles.

[0093] The present invention also relates to nanoparticles used according to the invention, wherein the intensity, power, or power density of the sound wave or radiation is between:

[0094] 0 and 10 100 10 -100 and 10 100 10 -10 and 10 10 10 -5 and 10 5 10 -3 and 10 3 or between 10 -1 And 10 watts,

[0095] 0 and 10 100 10 -100 and 10 100 10 -10 and 10 10 10 -5 and 10 5 10 -3 and 10 3 or between 10 -1 And 10 watts per centimeter, watts per square centimeter, or watts per cubic centimeter.

[0096] 0 and 10 100 10 -100 and 10 100 10 -10 and 10 10 10 -5 and 10 5 10 -3 and 10 3 or between 10 -1 And 10 watts per centimeter of body part, watts per square centimeter of body part, or watts per cubic centimeter of body part.

[0097] 0 and 10100 10 -100 and 10 100 10 -10 and 10 10 10 -5 and 10 5 10 -3 and 10 3 or between 10 -1 And 10 watts per centimeter transducer, watts per square centimeter transducer, or watts per cubic centimeter transducer.

[0098] 0 and 10 100 10 -100 and 10 100 10 -10 and 10 10 10 -5 and 10 5 10 -3 and 10 3 or between 10 -1 And 10 watts per gram of nanoparticles

[0099] The present invention also relates to nanoparticles used according to the invention, wherein the energy or energy density of the sound wave or radiation is less than:

[0100] i) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5 watt-second,

[0101] ii) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5 Watts per second per centimeter, Watts per second per square centimeter, or Watts per second per cubic centimeter.

[0102] iii) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5 Watts per second per centimeter of body part, Watts per second per square centimeter of body part, or Watts per second per cubic centimeter of body part.

[0103] iv) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5 Transducer with W / s per centimeter, W / s per square centimeter, or W / s per cubic centimeter.

[0104] v) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5 Joules

[0105] vi) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5 Joules per centimeter, joules per square centimeter, or joules per cubic centimeter.

[0106] vii) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5 joules per centimeter of body portion, joules per square centimeter of body portion, or joules per cubic centimeter of body portion.

[0107] viii) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5 joules per centimeter of transducer, joules per square centimeter of transducer, or joules per cubic centimeter of transducer.

[0108] ix) 10 9 10 6 10 5 10 3 , 100, 10, 1, 10 -1 10 -2 , or 10 -5Nanoparticles per joule,

[0109] In some cases, when the power of the sound wave is high and / or the application time of the sound wave is long, a value greater than 10 is preferred. -50 10 -10 10 -1 1, 5, 10, 10 5 Or 10 10 minute.

[0110] The present invention also relates to nanoparticles used according to the invention, wherein the energy or energy density of the sound wave or radiation is between:

[0111] i) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 10 4 watt-second,

[0112] ii) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 10 4 Watts per second per centimeter, Watts per second per square centimeter, or Watts per second per cubic centimeter.

[0113] iii) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 10 4 Watts per second per centimeter of body part, Watts per second per square centimeter of body part, or Watts per second per cubic centimeter of body part.

[0114] iv) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 10 4Transducer with W / s per centimeter, W / s per square centimeter, or W / s per cubic centimeter.

[0115] v) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 10 4 Joules

[0116] vi) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 10 4 Joules per centimeter, joules per square centimeter, or joules per cubic centimeter.

[0117] vii) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 10 4 joules per centimeter of body portion, joules per square centimeter of body portion, or joules per cubic centimeter of body portion.

[0118] viii) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 10 4 Joules per centimeter of transducer, Joules per square centimeter of transducer, or Joules per cubic centimeter of transducer, or

[0119] ix) 10 -50 and 10 50 10 -10 and 10 10 10 -5 and 10 5 10 -1 and 10 5 or between 1 and 104 joules per gram of nanoparticles,

[0120] In some cases, the power of the sound waves or the power of the radiation can be equal to 0 watts or 0 gray, preferably before, at the beginning, at the end, or after sound wave medical treatment, or after radiation medical treatment, or during some specific treatments or methods described in this invention, such as the treatment of anemia.

[0121] In some other cases, the power of the sound waves or radiation can be greater than 0 watts or 0 grays, preferably in sound wave medical procedures or radiation medical procedures.

[0122] The present invention also relates to nanoparticles used according to the invention, wherein the frequency of the sound wave or radiation is below 10. 5 Megahertz. In some cases, the frequency of sound waves or radiation can be below 10 MHz. 100 10 50 10 30 10 20 10 10 10 5 10 3 10 2 ,10,1,10 -1 10 -2 10 -3 10 -4 10 -5 10 -6 10 -7 10 -8 10 -10 or 10 -15 Megahertz or kilohertz.

[0123] In some other cases, the radiation or sound waves according to the invention may have a value greater than 10. -100 10 -50 10 -20 10 -10 10 -8 10 -7 10 -6 10 -5 10 -4 10 -3 10 -2 10 -1 , 1, 10, 10 3 10 5 or 10 10 Megahertz or kilohertz.

[0124] In other cases, the radiation or sound waves according to the invention can have a value between 10 and 10. -15 and 10 1510 megahertz -13 and 10 13 10 megahertz -11 and 10 11 10 megahertz -9 and 10 9 10 megahertz -7 and 10 7 10 megahertz -5 and 10 5 10 megahertz -3 and 10 3 megahertz, or between 10 -1 And 10 MHz.

[0125] In some cases, the frequency of sound waves or radiation can be the oscillation frequency of sound waves or radiation.

[0126] The present invention also relates to the use of nanoparticles in which the sound waves or radiation have a penetration depth, preferably in a body part, which is less than 10. 10 10 5 10 3 , 50, 50, 20, 10, 5, 1, 0.1 or 0.001 cm.

[0127] In some cases, the penetration depth of sound waves or radiation can have a penetration depth, preferably within the body, between 10... -10 and 10 10 10 -5 and 10 3 10 -3 and 10 3 10 -3 And 100, 10 -2 Between and 10, or between 10 -2 Between 10 and 10 centimeters.

[0128] The preferred penetration depth is that the sound wave or radiation penetrates or penetrates parts of the human body or nanoparticle regions, or penetrates or reaches 99%, 75%, 50%, 25%, 1%, 0.1%, or 10% of the target depth. -3 10 -9 Or 10 -20 The nanoparticle region, or the region separated from the body part or nanoparticle region by a device that will generate sound waves or radiation.

[0129] In one embodiment, the intensity, energy, power, and frequency of the sound wave or radiation are reduced, preferably by values ​​greater than 1.1, 1.2, 1.5, 2, 3, 5, 10, or 10. 2 10 3 10 5 Or 10 10The factor. Increased penetration depth, preferably acoustic or radiative, is preferred, especially through factors greater than 1.1, 1.2, 1.5, 2, 3, 5, 10, 10. 2 10 3 10 5 Or 10 10 Factors.

[0130] In one embodiment of the invention, the penetration depth of the sound wave or radiation is inversely proportional to the frequency of the sound wave or radiation. In some cases, the frequency of the sound wave or radiation can be reduced, preferably by a factor greater than 1.1, 1.2, 1.5, 2, 3, 5, 10, or 10. 2 10 3 10 5 Or 10 10 Preferably used to increase the penetration depth of sound waves or radiation, the preferred multiplier is greater than 1.1, 1.2, 1.5, 2, 3, 5, 10, or 10. 2 10 3 10 5 Or 10 10 Conversely, the frequency of the sound waves or radiation can be increased, preferably by a factor greater than 1.1, 1.2, 1.5, 2, 3, 5, 10, or 10. 2 10 3 10 5 Or 10 10 To reduce the penetration depth of sound waves or radiation, a multiplier factor greater than 0.1, 1.2, 1.5, 2, 3, 5, 10, or 10 is preferred. 2 10 3 10 5 Or 10 10 .

[0131] In one embodiment of the invention, unfocused sound waves or radiation are applied to a body part, which may include or include regions containing and / or not containing nanoparticles, and the nanoparticles and / or regions may include or include pathological cells and / or healthy cells.

[0132] In one embodiment of the invention, the unfocused sound waves or unfocused radiation coverage exceeds 10 percent. -5 10 -3 10 -1 , 1, 10, 10 3 Or 10 5 For body parts, use less than 10 3 10 2Applications or application points of 10, 5, 2, or 1. An application point can be defined as the acoustic or radiative volume that can be covered or targeted during a single application of sound waves or radiation or during a sequence of events (preferably during t1 or t3). In one embodiment of the invention, the acoustic volume or sound wave volume is defined as the volume exposed to sound waves or receiving sound wave energy or being acted upon by sound waves.

[0133] In one embodiment of the invention, radiation volume is defined as the volume exposed to radiation, receiving radiant energy, or being acted upon by radiation.

[0134] The present invention also relates to nanoparticles used according to the invention, wherein the sound waves or radiation are unfocused. In some cases, unfocused sound waves or radiation can be applied to a sound wave volume or radiation volume that includes a region or body portion of the nanoparticle, or a portion thereof.

[0135] In some cases, unfocused sound waves or radiation can be applied to the sound wave volume or radiation volume, where: i) greater than 10 -10 10 -3 10 -2 10 -1 , 1, 10, 10 2 10 3 10 5 Or 10 10 (ii) Greater than or equal to the nanoparticle region or body part or healthy site or diseased site, preferably greater than or equal to 1.1, 1.5, 2, 5, 10, 10 cubic centimeters. 3 Or 10 5 times, or greater than 1, 10, 10 3 10 5 Or 10 10 (iii) The volume of sound waves or radiation generated or resulting from the application of focused sound waves or radiation is larger than that generated or caused by the application of focused sound waves or radiation, preferably by a factor greater than or equal to 1.1, 1.5, 2, 5, 10, 10. 3 Or 10 5 Factors, or greater than 1, 10, 10 3 10 5 Or 10 10Cubic centimeters. In some cases, when unfocused sound waves or radiation are applied to areas including healthy cells, it is preferable not to damage or destroy the healthy cells, preferably because: i) the healthy cells do not come into contact with or mix with the nanoparticles, and the application of sound waves or radiation to both healthy cells and nanoparticles is a necessary condition for inducing the destruction of healthy cells, or ii) because healthy cells are less sensitive to sound waves or radiation or less easily destroyed by them compared to pathological cells. In other examples, this can be used to treat large body parts.

[0136] In some other cases, unfocused sound waves or radiation can be applied to the sound wave volume or radiation volume, namely: i) less than 10 100 10 50 10 20 10 10 10 5 10 3 , 10, 5, 2, 1, 10 -1 10 -3 Or 10 -5 (i) cubic centimeters, and (ii) below the nanoparticle region or body part or healthy or pathological site, preferably with a multiple factor greater than 1.1, 1.5, 2, 5, 10, or 10. 3 Or 10 5 or greater than 1, 10, 10 3 10 5 Or 10 10 Cubic centimeters. In some cases, the following may occur: i) applying unfocused sound waves or radiation to a relatively small area or volume, preferably avoiding potential toxicity due to applying sound waves or radiation to a large volume; ii) treating small body parts; or iii) avoiding the need to use equipment that is too large, too expensive, or too energy-intensive to generate sound waves or radiation.

[0137] In some other cases, unfocused sound waves or radiation can be applied to a sound wave or radiation volume, where the sound wave or radiation volume is: i) between 10 -100 and 10 100 cubic centimeters, between 10 -50 and 10 50 cubic centimeters, or between 10 -10 and 10 10 cubic centimeters, ii) the volume is less than 10 times smaller than the volume of body parts, nanoparticle regions, diseased sites and / or healthy sites. 100 10 10 10 5 10 3 10, 5, or 2 times larger than the volume of body parts, nanoparticle regions, diseased sites, and / or healthy sites, and 2, 5, 10, 10 times larger.3 10 5 10 10 Or 10 100 Between times.

[0138] In some other cases, unfocused sound waves or radiation can be applied to a sound wave or radiation volume that is larger than the volume of focused sound waves or radiation: i) in the range of 0 to 10 50 Between cubic centimeters, between 0 and 10 3 Between cubic centimeters, between 0 and 10 cubic centimeters, between 10 -50 and 10 50 Between cubic centimeters, within 10 -3 To about 10 3 Between cubic centimeters, or ii) between 1 and 10 50 Between 1 and 10 5 Between 1.1 and 10 50之间 Or in 1.1 and 10 5 between.

[0139] The present invention also relates to nanoparticles used according to the invention, wherein sound waves or radiation are focused. In this case, the sound waves or radiation are preferably applied to a sound wave volume or radiation volume preferably included in a body part, which is less than 0.001, 0.1, 1, 10, 10 2 10 3 10 5 Or 10 10 cubic centimeters.

[0140] In one embodiment of the invention, the focused sound waves or radiation can cover less than 10 percent. -5 10 -3 10 -1 , 1, 10, 10 3 Or 10 5 Body parts, using more than 10 3 10 2 10, 5, 2 or 1 application or application point

[0141] In some cases, the acoustic volume of the focused ultrasound wave can be a volume covered by or exposed to focused ultrasound, preferably high-intensity focused ultrasound (HIFU). In some cases, the acoustic volume can be the focal region of the acoustic volume. For high-intensity focused ultrasound (HIFU), a typical focal region (preferably a point) can be: i) an ellipsoidal or elliptical volume with a diameter of 1.5 mm and a beam axis of 15 mm, ii) or less than 10 mm. 5 10 3 100, 75 or 50 cubic millimeters.

[0142] In some cases, focused sound waves or focused ultrasound can be high-intensity focused ultrasound (HIFU).

[0143] In one embodiment of the invention, the sound wave is not a focused sound wave or a high-intensity focused ultrasound (HIFU).

[0144] In one embodiment of the invention, the radiation or sound wave has an intensity, power, strength, wavelength, or frequency that does not change with time and / or space.

[0145] In another embodiment of the invention, the radiation has an intensity, power, strength, wavelength, or frequency that varies with time and / or space.

[0146] In one embodiment of the invention, the radiation or sound wave has an intensity, power, or frequency that varies spatially. In some cases, the intensity, power, or frequency of the radiation varies by more than 10. -50 10 -20 10 -10 10 -5 10 -2 , 1, 10, 10 2 10 3 10 5 Or 10 10 Microtesla per square centimeter or microtesla per cubic centimeter or microtesla per gram of nanoparticles or watts per square centimeter or watts per cubic centimeter or watts per gram of nanoparticles or hertz per gram of square centimeter or hertz per centimeter or hertz per gram of nanoparticles.

[0147] In some cases, centimeters, square centimeters, and cubic centimeters can be specified as centimeters of body parts, square centimeters of body parts, and cubic centimeters of body parts, respectively.

[0148] In some other cases, 1 cubic centimeter of body portion may be specified as 1 gram of body portion.

[0149] In some cases, radiation or sound waves can have sufficiently high power, intensity, and / or frequency to preferably heat nanoparticles or induce the nanoparticles to generate free radicals or reactive substances, preferably with an intensity greater than 10. -100 10 -50 10 -20 10 -10 10 -3 10 -2 10 -1 1 or 10 millitalas, preferably with a frequency greater than 10. -100 10 -3 10 -2 10 -110, 50, 100 or 200 kHz, and / or preferably power greater than 10 -100 10 -6 10 -3 10 -1 , 1, 10, 10 3 Or 10 10 Watts (watts) or watts per square centimeter or watts per cubic centimeter or watts per gram of body part or watts per gram of nanoparticles or grays or grays per centimeter or grays per square centimeter or grays per cubic centimeter or grays per body part or grays per gram of nanoparticles.

[0150] In some other cases, radiation or sound waves may have power, intensity, and / or frequency kept below a certain threshold, preferably to avoid toxicity, such as that caused by scaling currents, excessive heating, or the generation of excessive free radicals or reactive substances; the intensity of the radiation may be below or kept below 10. 100 10 50 10 10 10 5 ,10,1,10 -1 Or 10 -5 millitalas. The frequency of radiation or sound waves can be below or remain below 10. 100 10 50 10 10 10 5 10 3 10, 1 or 10 -3 kilohertz. The power of the radiated or sound waves can be below or remain below 10 kilohertz. 100 10 50 10 20 10 10 10 5 10 3 ,10,1,10 -1 10 -3 Or 10 -6 Watts or Watts per centimeter or Watts per square centimeter or Watts per cubic centimeter or Watts per gram of body part or Watts per gram of nanoparticles or Gray or Gray per centimeter or Gray per square centimeter or Gray per cubic centimeter or Gray per body part or Gray per gram of nanoparticles.

[0151] In one embodiment of the invention, the excitation caused by radiation or sound waves from the nanoparticles, or preferably the radiation or sound waves applied to the nanoparticles or body parts, is continuous. In some cases, continuous application of radiation or sound waves refers to an application time greater than 10... -100 10 -50 10 -20 10 -10 10 -6 10 -3 10-1 1 or 10 3 The radiation or sound wave is applied continuously for a period of seconds, preferably longer than t1. In some other cases, the continuous application of radiation or sound waves is less than 10 seconds. 100 10 50 10 20 10 10 10 5 10 3 ,10,1,10 -1 Or 10 -5 Radiation is applied continuously for periods of seconds, days, months, or years.

[0152] In some other cases, nanoparticles can be nanoparticles exposed to radiation or sound waves.

[0153] In one embodiment of the invention, the nanoparticles are or belong to or are included in nanoparticles selected from the group consisting of: nanospheres, nanocapsules, dendritic polymers, carbon nanotubes, lipid / solid nanoparticles, lipid- or protein- or DNA- or RNA-based nanoparticles, nanoparticles having an internal aqueous environment surrounded by an outer layer, preferably a stable outer layer, most preferably a phospholipid layer, multilayer nanoparticles, polymer nanoparticles, quantum dots, metal nanoparticles, polymer micelles or nanoparticles, carbon-based nanostructures, nanobubbles, nanoparticles, cotton wool, nanopores, micropores, liposomes, viruses, preferably recombinant, herbal nanoparticles, antibodies, and vesicles.

[0154] In another embodiment of the invention, the nanoparticles are not, do not belong to, or are not included in at least one nanoparticle belonging to the group consisting of: nanospheres, nanocapsules, dendritic polymers, carbon nanotubes, lipid / solid nanoparticles, lipid- or protein- or DNA- or RNA-based nanoparticles, nanoparticles having an internal aqueous environment surrounded by an outer layer, preferably a stable outer layer, most preferably a phospholipid layer, multilayer nanoparticles, polymer nanoparticles, quantum dots, metal nanoparticles, polymer micelles or nanoparticles, carbon-based nanostructures, nanobubbles, nanoparticles, cotton wool, nanopores, micropores, liposomes, viruses, preferably recombinant, herbal nanoparticles, antibodies, and vesicles.

[0155] In some cases, nanoparticles can be in a liquid, gaseous, or solid state, preferably before, during, or after they are applied to or present in a part of the body.

[0156] In other cases, nanoparticles cannot be in one or both of the states of liquid, gas, or solid; preferably, they must be present, in, or after they are applied to a part of the body.

[0157] In other cases, nanoparticles can be assimilated or contained in ferromagnetic fluids, chemical or biological ferromagnetic fluids, wherein the chemical and biological ferromagnetic fluids are iron-containing fluids, preferably forming nanoparticles, which are prepared by chemical or biological synthesis, respectively.

[0158] In some other cases, the ferrofluid or nanoparticle assembly may comprise nanoparticles as well as excipients, solvents, matrices, gels, which preferably enable the nanoparticles to be applied to an individual or body part.

[0159] In some other cases, nanoparticles may include synthetic materials and / or biological materials and / or inorganic materials and / or organic materials.

[0160] In one embodiment of the invention, the nanoparticles are or refer to: i) a suspension of nanoparticles, ii) a composition containing nanoparticles, iii) an assembly of nanoparticles, iv) a region of nanoparticles, v) a mineral portion of nanoparticles, vi) an organic portion of nanoparticles, vii) an inorganic portion of nanoparticles, viiii) or a coating of nanoparticles.

[0161] In one embodiment of the invention, nanoparticles are defined as being greater than or containing 10 nanoparticles. -100 10 -50 10 -10 10 -5 10 -1 , 1, 10, 10 2 10 3 10 5 10 10 10 20 Or 10 50 Nanoparticles or milligrams of nanoparticles, or milligrams of iron contained in nanoparticles, or milligrams of nanoparticles per cubic centimeter or per cubic centimeter body portion of nanoparticles, or milligrams of iron contained in nanoparticles per cubic centimeter body portion of nanoparticles. In some cases, components, suspensions, or compositions containing a large number of nanoparticles can be used to induce or generate an increase in temperature, free radicals or reactive substances, or the dissociation of compounds from nanoparticles.

[0162] In another embodiment of the invention, one or more nanoparticles represent or contain less than 10 nanoparticles. 100 10 50 10 20 10 10 10 5 10 2 , 10, 1, 5, 2, 1, 10 -1 10 -5 10 -10Or 10 -50 Nanoparticles or milligram nanoparticles or milligram iron contained in nanoparticles or milligram nanoparticles per cubic centimeter or per cubic centimeter body portion of nanoparticles or milligram iron contained in nanoparticles per cubic centimeter body portion of nanoparticles assembly, suspension or composition. In some cases, assemblies, suspensions or compositions of nanoparticles containing a small amount of nanoparticles may be used to prevent toxicity.

[0163] In one embodiment of the invention, one or more nanoparticles or one or more nanoparticle assemblies may represent or be a region containing nanoparticles, a volume, surface, length, or the region where the nanoparticles are located. In some cases, the volume of the area occupied by the nanoparticles in the body portion is designated as the nanoparticle region.

[0164] In some cases, the nanoparticle region can be the volume occupied by a component of nanoparticles in a body part, wherein the nanoparticles are preferably smaller than 10 9 10 6 10 3 Or 10 nanometers spacing.

[0165] In some cases, nanoparticle assembly is a more general term than nanoparticle region, and can refer to any type of nanoparticle assembly before, during, or after the application of nanoparticles to a part of the body.

[0166] In some cases, the separation distance between nanoparticles within a nanoparticle assembly or nanoparticle region may correspond to the average or maximum distance that separates the nanoparticles within the assembly.

[0167] In some cases, the distribution of the spacing between nanoparticles can highlight the presence of a small number of nanoparticles, preferably less than 50%, 10%, 1%, or 10%. -2 Or 10 -5 The total number of nanoparticles in an individual may have a small separation distance, i.e., the separation distance is preferably less than 10. 9 10 6 10 3 The spacing can be 10 nanometers or have a larger separation distance, preferably greater than 10 nanometers. 9 10 6 10 3 Or 10 nanometers. In this case, it is preferable to disregard the presence of these few nanoparticles in order to estimate the average or maximum separation distance between the nanoparticles.

[0168] The present invention also relates to nanoparticles used according to the invention, wherein the nanoparticles are crystalline, metallic, or magnetic.

[0169] In one embodiment of the invention, the nanoparticles are crystalline. In this case, they preferably have a density greater than or at least 1, 2, 10, 10. 2 10 3 10 6 Or 10 9 Crystal planes or regular atomic arrangements, preferably observable with an electron microscope.

[0170] In one embodiment of the invention, the nanoparticles are metallic. In this case, they contain at least 1, 10, 10 3 10 5 Or 10 9 The nanoparticles contain at least 1%, 10%, 50%, 75%, or 90% metal atoms, wherein this percentage can be the ratio of the number or mass of metal atoms in the nanoparticles to the total number or mass of all atoms in the nanoparticles. The nanoparticles, preferably metal oxide nanoparticles, may also contain at least 10%, ... 3 10 5 Or 10 9 100% oxygen atoms or containing at least 1%, 10%, 50%, 75%, or 90% oxygen atoms, wherein the percentage can be the number or mass of oxygen atoms in the nanoparticle divided by the total number or mass of all atoms in the nanoparticle.

[0171] In another embodiment of the invention, the metal or metal atoms are selected from: lithium, beryllium, magnesium, aluminum, potassium, calcium, scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, rubidium, strontium, yttrium, zirconium, niobium, molybdenum, technetium, ruthenium, rhodium, palladium, silver, cadmium, indium, tin, cesium, barium, lanthanum, cerium, praseodymium, neodymium, isopropylidene, samarium, europium. Gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, hafnium, tantalum, tungsten, rhenium, osmium, iridium, platinum, gold, mercury, thallium, lead, bismuth, polonium, francium, radium, actinium, thorium, protactinium, uranium, neptunium, plutonium, americium, curium, beryl, californium, einsteinium, fermium, menthium, noreium, ruthenium, ruthenium, α, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, β, and β.

[0172] In another embodiment of the invention, the nanoparticles contain less than 1, 10, 10 3 10 5 Or 10 9 It may contain less than 1%, 10%, 50%, 75%, or 90% of metal atoms, where the percentage can be the number or mass of metal atoms in the nanoparticle divided by the total number or mass of all atoms in the nanoparticle. It may also contain less than 1%, 10 ... 3 10 5 Or 10 910% or less than 1%, 10%, 50%, 75% or 90% of oxygen atoms, where the percentage can be the number or mass of oxygen atoms in the nanoparticle divided by the total number or mass of all atoms in the nanoparticle.

[0173] In one embodiment of the invention, when the nanoparticles have magnetic behavior or properties, the nanoparticles are magnetic, wherein the magnetic behavior or properties are preferably selected from diamagnetic, superparamagnetic, paramagnetic, ferromagnetic, and ferrimagnetic behaviors or properties.

[0174] In some cases, magnetic behavior or properties can be observed or exist below the following temperatures: i) 10 5 10 3 ii) Curie temperature, or iii) blocking temperature.

[0175] In some other cases, magnetic behavior or properties can be observed or exist at temperatures above the following: i) 0.5, 1, 10, 20, 50, 100, 200, 350, 500, 10 3 Or 10 5 (i) Open, (ii) Curie temperature, or (iii) Blocking temperature.

[0176] In other cases, magnetic behavior or properties can be between 10 -20 and 10 20 It is observed or present at temperatures between 0.1 and 1000 K, or at temperatures between 0.1 and 1000 K.

[0177] In one embodiment of the invention, the nanoparticles have or can be characterized by at least one of the following properties: i) the presence of a core, preferably magnetic, preferably mineral, preferably composed of a metal oxide (e.g., iron oxide), most preferably maghemite or magnetite, or an intermediate component between maghemite and magnetite; ii) the presence of a coating surrounding the core and preferably preventing the nanoparticles from agglomerating, preferably enabling the nanoparticles to be applied to a living organism or body part or stabilizing the nanoparticle core, wherein the coating thickness may preferably be between 0.1 nm and 10 μm, between 0.1 nm and 1 μm, between 0.1 nm and 100 nm, between 0.1 nm and 10 nm, or between 1 nm and 5 nm; iii) the magnetic properties causing diamagnetic, paramagnetic, superparamagnetic, ferromagnetic, or ferrimagnetic behavior; iv) a coercivity greater than 0.01, 0.1, 1, 10, 100, 10 3 10 4 10 5 10 9 Or 10 20v) The ratio between remanent magnetization and saturation magnetization is greater than 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 0.9, or 0.99; vi) Saturation magnetization is greater than 0.1, 1, 5, 10, or 50 g-electron mass units; vii) Magnetic properties such as coercivity, remanent magnetization, and saturation magnetization are preferably measured or observed at temperatures greater than 0.1 K, 1 K, 10 K, 20 K, 50 K, 100 K, 200 K, 300 K, 350 K, and 3000 K; viiii) Crystallinity, i.e., the nanoparticles preferably have a crystallinity of at least 1, 2, 5, 10, or 100 K. 1) Crystalline facets, preferably observable or measurable by an electron microscope; ix) Presence of single domains; x) Greater than 0.1, 0.5, 1.5, 10, 15, 20, 25, 30, 50, 60, 70, 80, 100, 120, 150, or 200 nanometers; xi) Size between 0.1 nanometers and 10 micrometers, 0.1 nanometers and 1 micrometer, 0.1 nanometers and 100 nanometers, 1 nanometer and 100 nanometers, or 5 nanometers and 80 nanometers; xii) Nonpyrogenic or pyrogenic, preferably referring to an endotoxin concentration of less than 10 ppm in the nanoparticles. 20 10,000, 1,000, 100, 50, 10, 5, 2 or 1 unit of endotoxin per milligram of nanoparticle or milligrams of iron contained in the nanoparticle, meaning that the nanoparticle, when applied to a living organism or part of the body, does not induce fever or an increase in whole-body temperature greater than 100, 50, 6.6, 5, 3, 2 or 1 degrees Celsius; xiii) synthesized in living organism, preferably by bacteria; xiv) chemically synthesized; xv) less than 50%, 25%, 15%, 10%, 5%, 2% or 1% of the organic or carbon material used for synthesis is derived from the living organism used for synthesis; xv) greater than 99%, 95%, 80%, 70%, 60%, 50% or 25% of the mineral material present is derived from the living organism used for synthesis; or xvi) a specific absorbance (SAR) greater than 1, 10, 1000 or 10 4 Watts per gram of nanoparticles are preferably measured under an alternating magnetic field with an intensity greater than 0.1, 1, 10, or 100 millitalas and / or a frequency greater than 1, 10, 100, or 1000 kilohertz, or alternatively preferably under the application of sound waves, and optionally under radiation such as electromagnetic sound or light radiation.

[0178] In some cases, the synthesized organisms can be magnetotactic bacteria, other types of bacteria besides magnetotactic bacteria or enzymes of certain bacteria, which preferably synthesize nanoparticles extracellularly, such as Mycobacterium paratuberculosis, Lactobacillus shewani, fermenting terrestrial fungi, ants, fungi, or various plants.

[0179] In another embodiment of the invention, the nanoparticles have or are characterized by at least one of the following properties: i) coercivity less than 0.01, 0.1, 1, 10, 100, 10 3 10 4 10 5 10 9 Or 10 20 ii) Saturation magnetization less than 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 0.9, or 0.99; iii) Saturation magnetization less than 0.1, 1, 5, 10, 50, 200, 1000, or 5000 g electron mass units; iv) Magnetic properties preferably measured or observed at temperatures below 0.1 K, 1 K, 10 K, 20 K, 50 K, 100 K, 200 K, 300 K, 350 K, and 3000 K; v) Size less than 0.1, 0.5, 1.5, 10, 15, 20, 25, 30, 50, 60, 70, 80, 100, 120, 150, or 200 K. Nanoscale, vi) contains more than 10, 5, 2 or 1 percent of the organic or carbon material derived from a synthetic living organism; vii) contains less than 99, 95, 80, 70, 60, 50 or 25 percent of the organic or carbon material derived from the living organism used for synthesis; or xi) has a specific absorbance (SAR) of less than 1, 10, 1000 or 10 4 The watt-per-gram nanoparticles are preferably grown in an alternating magnetic field with an intensity below 0.1, 1, 10, or 100, 200, 500, 10. 3 Or 10 5 millitas and / or frequencies below 1, 10, 100, 10 3 10 5 Or 10 9 Measurements can be taken at kilohertz, or preferably under the application of sound waves, or alternatively under radiation such as electromagnetic sound or light radiation.

[0180] In some cases, the mineral may be the portion of nanoparticles or magnetic particles that does not contain organic material, or may contain a low mass percentage of organic material, preferably less than 100%, 99%, 50%, 20%, 10%, 5%, 1%, or 10%. -1 % or 10 -2 %. The mineral is preferably the core of nanoparticles.

[0181] In some other cases, minerals may contain more than 0% organic material by mass, 10 -50 %, 10 -10 %, 10 -2 %, 10 -1% or percentage in the mass of organic material. This can be when the purification step fails to remove the organic material or when organic material is added to the mineral after the purification step.

[0182] In some cases, nanoparticles may be surrounded by a coating. This coating may be made of synthetic, organic, or inorganic materials, or of substances containing one of the following functional groups: carboxylic acids, phosphoric acid-functional substances, sulfonic acids, esters, amides, ketones, alcohols, phenols, thiols, amines, ethers, sulfides, acyl halides, amidines, amides, nitriles, hydroperoxides, imines, aldehydes, and peroxides. In some cases, the coating may be made of carboxy-methyl-dextran, citric acid, phosphatidylcholine, or oleic acid. In some cases, the coating may disperse the nanoparticles in a matrix or solvent such as water, preferably without agglomeration or precipitation of the nanoparticles. In some cases, the coating may enable the nanoparticles to be internalized within cells. In some other cases, the coating may cause: i) two or more nanoparticles to preferably be chained together, ii) nanoparticle aggregation to be prevented, and / or iii) a uniform nanoparticle distribution to be obtained.

[0183] In one embodiment of the invention, the nanoparticles are heat-free. Preferably, the non-pyrogenic nanoparticles comprise: i) less than 10 100 10 50 10 20 10 8 10 5 10 3 1) or 10 endotoxin units or thermotoxin units per cubic centimeter of body part or per milligram nanoparticle endotoxin unit or endotoxin units per cubic centimeter of body part per milligram nanoparticle, or ii) causing an increase in temperature of less than 10 degrees Celsius in an individual or body part. 5 10 3 10 2 The temperature is 50, 10, 5, 4, 3, 2 or 1 degree Celsius, preferably above physiological temperature, and preferably before or after the application of sound waves or radiation to the nanoparticles or without application.

[0184] In one embodiment of the invention, the nanoparticles or compounds are composed of or include chemical elements selected from or comprising: metals (alkali metals, alkaline earth metals, transition metals), half-metals, non-metals (halogens, rare gases), chalcogens, lanthanides, and actinides.

[0185] In another embodiment of the invention, the nanoparticles or compounds are composed of or comprise chemical elements selected from the group consisting of: hydrogen, lithium, sodium, potassium, rubidium, cesium, francium, beryllium, magnesium, calcium, strontium, barium, radium, scandium, yttrium, lanthanides, actinides, titanium, zirconium, hafnium, rubidium, vanadium, niobium, tantalum, hafnium, chromium, molybdenum, tungsten, niobium, manganese, technetium, rhenium, iron, ruthenium, osmium, holmium, dysprosium, cobalt. Rhodium, iridium, cerium, nickel, palladium, platinum, dysprosium, copper, silver, gold, ruthenium, zinc, cadmium, mercury, copper, boron, aluminum, gallium, indium, thallium, yttrium, carbon, silicon, germanium, tin, lead, azodium, nitrogen, phosphorus, arsenic, antimony, bismuth, fluorine, chlorine, bromine, iodine, astatine, argon, helium, neon, fluorine, bromine, argon, krypton, xenon, radon, auburn, lanthanum, cerium, praseodymium, neodymium, berylene, californium, europium, einium, fermium, mendeium, thyrathiamine, and ruthenium.

[0186] In some cases, nanoparticles or compounds may also consist of or include alloys, mixtures or oxides of these chemical elements.

[0187] In some cases, nanoparticles or compounds can consist of more than 10 -50 10 -20 10 -10 10 -5 10 -2 It consists of one or more elements at percentages of 1, 5, 10, 50, 75, 80, 90, 95, or 99. This percentage can represent the mass or quantity of such chemical element contained in the nanoparticle or compound divided by the total number or total mass of all chemical elements contained in the nanoparticle or compound, or the total mass of the nanoparticle or compound.

[0188] In some other cases, nanoparticles or compounds may consist of or contain less than 10 -50 10 -20 10 -10 10 -5 10 -2 The percentage of these chemical elements is 1, 5, 10, 50, 75, 80, 90, 95, or 99.

[0189] In some other cases, these chemical elements are contained within nanoparticles or compounds, or on the surface of nanoparticles or compounds, or in the mineral or central portion of nanoparticles or compounds, or in the coating of nanoparticles or compounds.

[0190] In one embodiment of the invention, the nanoparticles or compounds do not include or contain at least one chemical element belonging to the group selected from: metals (alkali metals, alkaline earth metals, transition metals), half-metals, non-metals (halogens, rare gases), chalcogens, lanthanides, and actinides.

[0191] In another embodiment of the invention, the nanoparticles or compounds contain no or no chemical element selected from at least one of the following: hydrogen, lithium, sodium, potassium, rubidium, cesium, francium, beryllium, magnesium, calcium, strontium, barium, radium, scandium, yttrium, lanthanides, actinides, titanium, zirconium, hafnium, rubidium, vanadium, niobium, tantalum, hafnium, chromium, molybdenum, tungsten, niobium, manganese, technetium, rhenium, iron, ruthenium, osmium, holmium, dysprosium, cobalt. Rhodium, iridium, cerium, nickel, palladium, platinum, dysprosium, copper, silver, gold, ruthenium, zinc, cadmium, mercury, copper, boron, aluminum, gallium, indium, thallium, yttrium, carbon, silicon, germanium, tin, lead, azodium, nitrogen, phosphorus, arsenic, antimony, bismuth, fluorine, chlorine, bromine, iodine, astatine, argon, helium, neon, fluorine, bromine, argon, krypton, xenon, radon, auburn, lanthanum, cerium, praseodymium, neodymium, berylene, californium, europium, einium, fermium, mendeium, thyrathiamine, and ruthenium.

[0192] In another embodiment of the invention, the nanoparticles or compounds do not contain or consist of alloys, mixtures or oxides of the chemical elements(s).

[0193] In one embodiment of the invention, nanoparticles are defined as particles with a size greater than 10 in one dimension. -1 The sizes of nanoparticles are 1, 2, 5, 10, 20, 50, 70, 100, 200, or 500 nanometers. Larger nanoparticles can possess greater coercivity and / or greater remanent magnetization, and / or can absorb the energy or power of sound waves more strongly or more effectively than nanoparticles with smaller sizes. In some cases, the energy or power absorbed by nanoparticles increases with the size of the nanoparticles, being greater than 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 10 nanometers. 3 10 5 Or 10 7 The factor increases, and is greater than 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 10 5 Or 10 7 The factor increases,

[0194] In another embodiment of the invention, nanoparticles are defined as having a size less than 10 in one dimension. 4 10 3 10 2 10, 1 or 10 -1 Nanoparticles. Nanoparticles with smaller sizes can be more easily administered, such as via intravenous injection, or certain toxic effects, such as embolism, can be avoided.

[0195] In another embodiment of the invention, the nanoparticle size is between 10... -2 and 10 20 nanometers, 10 -2 and 10 4Nanometers, 10 -1 and 10 3 Nano or between 1 and 10 2 Between nanometers. This can be when nanoparticles or nanoparticle components have a well-defined, preferably narrow, size distribution.

[0196] In another embodiment of the invention, the nanoparticle size distribution is less than 1000, 100, 75, 50, 25, 10, 5, 2, or 1 nanometer. A narrow nanoparticle size distribution can be desired to prevent aggregation or to facilitate the nanoparticles' chain-like organization.

[0197] In another embodiment of the invention, the nanoparticle size distribution is greater than 1000, 100, 75, 50, 25, 10, 5, 2, or 1 nanometer. A large nanoparticle size distribution, in some cases, allows the nanoparticles to be removed more quickly.

[0198] In another embodiment of the invention, the nanoparticles have a surface charge greater than -200, -100, -50, -10, -5, 0.1, 1, 2, 5, 10, 50 or 100 millivolts, preferably at pH values ​​below 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1, 12, 13 or 14. The nanoparticles can have a large surface charge at low pH values ​​when the coating they are coated with can achieve this charge without being damaged.

[0199] In another embodiment of the invention, the nanoparticles have a surface charge of less than -200, -100, -50, -10, -5, 0.1, 1, 2, 5, 10, 50 or 100 millivolts, preferably at a pH value greater than 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14. The nanoparticles can have a low surface charge at high pH values ​​when the coating they are coated with can achieve this charge without being damaged.

[0200] In another embodiment of the invention, the nanoparticles have a surface charge comprising +200 and -200 millivolts, +100 and -100 millivolts, +50 and -50 millivolts, +40 and 40 millivolts, +20 and -20 millivolts, +10 and -10 millivolts, or between +5 and -5 millivolts, preferably at a pH value below 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14.

[0201] In another embodiment of the invention, the nanoparticles have a surface charge comprising +200 and -200 millivolts, +100 and -100 millivolts, +50 and -50 millivolts, +40 and -40 millivolts, +20 and -20 millivolts, +10 and -10 millivolts, or between +5 and -5 millivolts, preferably at a pH value higher than 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14.

[0202] In another embodiment of the invention, the nanoparticles have a weight or mass preferably expressed in units such as grams, kilograms, or milligrams. One gram of nanoparticles may be one gram of metal, such as iron contained within the nanoparticles. The mass or weight of the nanoparticles may correspond to the mass or weight of a single nanoparticle or the mass or weight of a component of nanoparticles.

[0203] In one embodiment, the mass of the nanoparticles is greater than 10. -20 10 -10 10 -5 10 -2 , 1, 10, 10 3 10 9 Or 10 20 In some cases, a larger mass of nanoparticles can be expected to increase the energy of the sound waves absorbed by the nanoparticles.

[0204] In one embodiment, the mass of the nanoparticles is less than 10. -20 10 -10 10 -5 10 -2 , 1, 10, 10 3 10 9 Or 10 20 In some cases, low nanoparticle mass can be desirable to prevent or minimize nanoparticle toxicity.

[0205] In one embodiment of the invention, the nanoparticles, suspension, composition, or assembly of nanoparticles are stable, preferably for a period of time, and preferably with a stability duration greater than 10. -10 5, 10, 10 50 Or 10 100Minutes. In some cases, nanoparticles, suspensions, compositions, or assemblies of nanoparticles are stable when greater than 1, 5, 10, 50, 100, 200, 500, or 1000 mg of nanoparticles per milliliter of solvent, matrix, or body portion surrounds or contains nanoparticles. In some cases, nanoparticles, said suspensions, compositions, or assemblies of nanoparticles are stable if: i) the nanoparticles do not degrade or lose part or all of their coating or are applicable to the body portion; or ii) the optical density of the suspension, composition, or nanoparticles decreases, preferably measured at 480 nm or another fixed wavelength, by no more than 1%, 5%, 10%, 50%, 75%, or 90%, or greater than 10%. -10 10 -3 10 -1 0.5 or 0.7, 1, 5, 10, 10 after homogenization or mixing or optical density measurement or absorption measurement of the suspension or composition. 3 10 7 Or 10 20 Within seconds. This percentage can be equal to (OD). B -OD A ) / OD B or OD A / OD B , of which OD B OD refers to the optical density of nanoparticles, suspensions, components, or components measured prior to optical density or absorption measurements of homogenized or mixed nanoparticles, suspensions, compositions, or components. A The optical density of nanoparticles, suspensions, components, or components is measured after homogenization or mixing, or after absorption measurements of the optical density or absorption of nanoparticles, suspensions, components, or components.

[0206] In some cases, nanoparticles can be suspended in a liquid or dispersed in a matrix or body part to produce a uniform nanoparticle dispersion or a highly stable nanoparticle composition or suspension.

[0207] In one embodiment of the invention, the nanoparticles are arranged in a chain and contain more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35 or 40 nanoparticles.

[0208] In another embodiment of the invention, the nanoparticles are arranged in chains having: i) a length less than 2.10 mm. 10 2.10 5 2.10 3 Or 2.10 2 (ii) The number of nanoparticles in each chain is less than 2, 5, 10, 10 2 Or 10 3In some cases, short-chain nanoparticles are desirable or available, for example, after the chains are partially or completely broken, which facilitates the internalization of nanoparticles into cells.

[0209] In another embodiment of the invention, the nanoparticles are arranged in chains having a length greater than 10. -1 , 1, 5, 10, 2.10 2 2.10 3 Or 2.10 5 (ii) The number of nanoparticles in each chain is less than 2, 5, 10, 10 2 Or 10 3 In some cases, long-chain nanoparticles are desired or available to increase the amount of heat or compounds dissociated from nanoparticles under the application of sound waves or radiation, or to prevent nanoparticle aggregation or achieve a uniform distribution of nanoparticles.

[0210] In another embodiment of the invention, the nanoparticles are arranged in chains, said chains having: i) a length of 10 -1 and 10 10 Nanometers or between 1 and 10 5 Between nanometers, or ii) the number of nanoparticles in each chain is between 2 and 10. 5 2 and 10 3 or between 2 and 50

[0211] In another embodiment of the invention, the nanoparticles are arranged into a chain when they are combined or connected to each other or when the crystallization directions of two adjacent nanoparticles in the chain are aligned, wherein the alignment is preferably characterized by an angle of less than 90, 80, 70, 60, 50, 20, 10, 3 or 2 (degrees) between two crystallization directions belonging to two adjacent nanoparticles in the chain.

[0212] Preferably, when the nanoparticles are biosynthesized, the nanoparticles can be in chains: i) within the organism in which they are generated, also designated as a synthetic living organism, or ii) outside the organism. Preferably, the nanoparticles are distributed in chains before or after they are extracted or separated from the organism.

[0213] In one embodiment of the invention, the nanoparticles are not arranged in a chain-like pattern.

[0214] In another embodiment of the invention, when the production of nanoparticles involves or is attributable to a living organism in fewer than 1, 2, 5, 10, or 100 steps, such as the crystallization of iron oxide, the stabilization of nanoparticles, the organization of nanoparticles, the nanoparticles are chemically synthesized or not synthesized by a living organism. In some cases, chemical synthesis can be defined as involving multiple steps, or more than 1%, 2%, 5%, 25%, 50%, 75%, or 90% of the steps, which involve the occurrence of a chemical reaction without involving a living organism or a portion thereof, such as DNA, RNA, proteins, enzymes, or lipids.

[0215] In another embodiment of the invention, chemical synthesis can be used to generate chemical substances or compounds for simulating, replicating, or remanufacturing compartments, organelles, or other biological materials, wherein the chemical synthesis or compound can be used or can lead to the generation of nanoparticles. In some cases, the compartments, organelles, or other biological materials can be lysosomes, endosomes, vesicles, preferably biological materials, having the ability or function to dissolve or convert crystalline iron into free iron or to convert free iron into crystalline iron. In some cases, this conversion is partial and preferably leads to the destruction or formation of a partial crystalline assembly of iron atoms or ions, wherein the mixture of crystalline iron and amorphous iron is preferably a mixture of crystalline iron and amorphous iron, at least one of which is a mixture of crystalline iron and amorphous iron. In some cases, crystalline iron can be defined as the assembly of iron atoms or ions that result in the presence of crystalline planes, preferably observed using transmission or scanning electron microscopy as a characterization method; free iron can preferably be defined as one of several iron atoms or ions that do not result in the presence of crystalline planes, preferably highlighted by the absence of diffraction patterns, using, for example, transmission or scanning electron microscopy as a characterization method.

[0216] In one embodiment of the invention, the nanoparticles are biosynthesized or biosynthesized from living organisms, wherein the living organism is specified as a synthetic living organism, which preferably comprises or contains at least 1, 2, 5, 10, 10 3 10 6 Or 10 9 It consists of a eukaryotic cell, a prokaryotic cell, or a portion of such cells. In some cases, a portion of a eukaryotic or prokaryotic cell may be biological material produced by or derived from such cells, such as RNA, DNA, organelles, nucleosomes, nucleosomes, ribosomes, vesicles, rough endoplasmic reticulum, Golgi apparatus, cytoskeleton, smooth endoplasmic reticulum, mitochondria, vacuoles, cytosol, lysosomes, centroid, and cell membrane. In some cases, biosynthesis can be defined as a synthesis involving multiple steps, or more than 1, 2, 5, or 10 steps, or more than 1%, 2, 5, 25, 50, 75, or 90 percent of the steps involving at least 1, 2, 10, or 10 steps.3 10 6 Chemical reactions that occur with the participation of living organisms or parts of organisms such as DNA, RNA, proteins, enzymes, and lipids.

[0217] In another embodiment of the invention, nanoparticles are synthesized or produced or crystallized or assembled or transformed into nanoparticles or other biological materials, such as proteins, lipids, enzymes, DNA or RNA, through compartments, organelles, preferably generated or derived from eukaryotic or prokaryotic cells.

[0218] In another embodiment of the invention, the nanoparticles are synthesized from or in at least one eukaryotic cell, prokaryotic cell, or a portion thereof.

[0219] In another embodiment of the invention, the nanoparticles are synthesized therefrom or therein: i) the matrix or medium or environment is located outside at least one eukaryotic cell, prokaryotic cell or part of such cell, or ii) an extracellular matrix.

[0220] In one embodiment of the invention, when at least 1, 2, 5, 10, or 100 production steps, such as the crystallization of iron oxide, stabilization of iron oxide minerals, and organization, such as forming chains or aggregates, involve or are attributed to a living organism, the nanoparticles are synthesized from a living organism.

[0221] The present invention also relates to the use of nanoparticles, wherein the nanoparticles are synthesized by magnetotactic bacteria, extracted from magnetotactic bacteria, derived from, or isolated from magnetosomes.

[0222] In one embodiment of the invention, the magnetotactic bacteria are selected from the group consisting of: magnetospirobacter strain AMB-1, magnetococcus strain MC-1, three facultative anaerobic Vibrio strains MV-1, MV-2 and MV-4, magnetospirobacterial strain MS-1, spirospirobacter gasseri MSR-1, facultative anaerobic magnetotactic spirobacterium, magnetobacterium magnetospirobacter MGT-1, obligate anaerobic bacteria, and desulfurized magnetospirobacterium RS-1.

[0223] In one embodiment of the invention, magnetotactic bacteria are defined as bacteria capable of synthesizing magnetocytosomes, wherein these magnetocytosomes are preferably characterized by at least one of the following properties: i) they are produced intracellularly, ii) they are magnetic, iii) they contain minerals, iv) their core is preferably composed of metal oxides (such as iron oxide), v) their core is surrounded by biological material, such as lipids, proteins, endotoxins, which are preferably removable, vi) they are arranged in chains, vii) they generate heat under the action of an alternating magnetic field.

[0224] In one embodiment of the invention, the magnetic core and the nanoparticle share one or more properties, such as at least one magnetic property, size, composition, chain arrangement, charge, core, mineral, coating, or crystallization property.

[0225] In one embodiment of the invention, the magnetosome comprises a mineral portion synthesized by magnetotactic bacteria, preferably crystalline iron oxide produced by these bacteria. In this case, the magnetosome or the magnetosome mineral portion produced by these bacteria preferably does not contain proteins, lipids, endotoxins, or carbon-containing biological materials, or does not contain more than or less than 0.1, 1, 10, 30, 50, or 75% carbon by mass.

[0226] This invention also relates to the use of nanoparticles, wherein the nanoparticles are or are chemical analogs of magnetosomes, such as iron oxide nanoparticles known as Sigma nanoparticles (reference: 637106-25G), SPION20 (nanomag®-D-spio 20, reference 79-02-201), SPION50 (synomag-D50, reference: 104-000-501), SPION100 (nanomag®-D-spio 100, reference: 79-00-102), or nanoparticles synthesized using methods similar to these nanoparticles, but producing improved or additional properties, such as chain arrangement. In some cases, the chemical analogs of magnetosomes may be chemically synthesized and / or not synthesized by magnetotactic bacteria.

[0227] In some cases, the chemical analogues of the magnetic particles share at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 common properties with the magnetic particles, wherein these common properties are preferably ferrimagnetic behavior, and preferably have a coercivity greater than 10 at temperatures preferably greater than 0, 5, 10, 50, 100, 200, 300, 500, or 1000 K. -50 10 -10 10 -2 1, 5, 10 or 100 Oersted, larger size, preferably larger than 1, 5, 10, 20, 50 or 70 nanometers, and / or chain arrangement, preferably more than 1, 2, 5 or 10 nanoparticles arranged in a chain.

[0228] In one embodiment of the invention, the nanoparticles or magnetosomes are purified to remove more than 10%, 50%, or 90% or more of endotoxins and / or other biological material, such as proteins or lipids derived from synthetic living or magnetotactic bacteria. In some other cases, the nanoparticles or magnetosomes are purified to remove less than 100%, 99.9%, 99%, 95%, or 90% of the mass percentage of endotoxins and / or other biological material. The purification step preferably produces purified nanoparticles or magnetosomes. In some cases, this percentage may be equal to... Or Q AP / Q BP Q BP and Q AP These refer to the amounts of endotoxin, biological material, protein, or lipid before and after the purification step.

[0229] In some cases, the purification step may include using a method or one or more detergents (e.g., NaOH and / or KOH), preferably mixed with synthetic living organisms or magnetotactic bacteria or bacterial fragments, preferably removing organic matter or separating organic materials from inorganic materials contained in nanoparticles or magnetosomes, and then preferably able to collect, preferably contained in nanoparticles or magnetosomes.

[0230] In some cases, the purified nanoparticles or magnetic bodies are mineral nanoparticles or magnetic bodies.

[0231] In one embodiment of the invention, the nanoparticles according to the invention are pharmaceuticals, medical devices, cosmetic products, biological products, products for research purposes, or products for determining the properties of biological samples.

[0232] In one embodiment of the invention, the nanoparticles are acoustic sensitizers, preferably used in sonodynamic therapy.

[0233] In one embodiment of the invention, the sound-sensitizing agent is defined as a substance that enhances the effect of sound waves, i.e., a substance that increases the quantity of biological material, preferably pathological cells, causing them to die, be destroyed, denatured, or inactivated, preferably at a concentration of 1.2, 1.5, 2, 5, 10, or 10. 3 Or 10 5 Factors and / or substances that reduce the number of healthy cells, preferably administered during treatment at doses of 1.2, 1.5, 2, 5, 10, 10. 3 Or 10 5Factors cause it to die, be destroyed, denature, or become inactive. In some cases, a sound-sensitive agent can also be defined as a substance that causes a temperature increase under the action of sound waves, and this temperature increase is greater in the presence of the sound-sensitive agent than in the absence of the sound-sensitive agent; that is, the temperature increase in the presence of the sound-sensitive agent is preferably greater than 10% compared to the absence of the sound-sensitive agent. -100 10 -50 10 -10 10 -5 The concentration of the sound-sensitive agent is preferably greater than 10 °C, at 0.1, 1, 2, 5, 10, 20, or 50 °C. -50 10 -9 10 -6 10 -3 10 -1 1, 10, 100 or 10 3 The concentration is measured in milligrams per milliliter or per cubic centimeter of body portion. In some other cases, a sound sensitizer can also be defined as a substance that causes a compound to dissociate under the influence of sound waves, a situation that is more pronounced in the presence of the sound sensitizer than in its absence. In the presence of the sound sensitizer, the percentage of dissociated compound is preferably 0.1, 1, 2, 5, 10, 20, 50, 75, 80, or 90% greater than in the absence of the sound sensitizer. The concentration of the sound sensitizer is preferably greater than 10 mg / mL. -9 10 -6 10 -3 10 -1 1, 10, 100 or 10 3 Milligrams are measured per milliliter or per cubic centimeter of body volume.

[0234] In another embodiment of the invention, the nanoparticles, nanoparticle suspension, or component or composition have a concentration, preferably expressed in units such as grams, kilograms, or milligrams, for nanoparticles, metals, metallic chemical elements, iron, iron oxide, malachite, magnetite, per unit volume such as liters, milliliters, cubic centimeters, or cubic meters, or per unit surface area or unit length. This concentration is preferably the concentration before or after application to a body part, wherein the volume, surface area, or length is preferably the volume, surface area, or length of the nanoparticle suspension, component, or composition before or after application, or the volume, surface area, or length of the body part.

[0235] The present invention also relates to nanoparticles used according to the invention, wherein the concentration of the nanoparticles, preferably exposed to or having sound waves or radiation applied thereto, preferably located in a body part or nanoparticle region, is less than 10 grams of nanoparticles per cubic centimeter or grams of iron contained in the nanoparticles per cubic centimeter of body part. In some cases, the nanoparticle concentration may be less than 10. 50 10 20 10 1010 5 10 3 10 2 , 10, 5, 2, 1, 10 -3 10 -6 Or 10 -9 The concentration of nanoparticles per cubic centimeter or per cubic centimeter of body portion is measured per cubic centimeter or per cubic centimeter of body portion. Low concentrations of nanoparticles may be necessary or desirable to prevent toxicity that may occur at high concentrations of nanoparticles.

[0236] The present invention also relates to nanoparticles used according to the invention, wherein the concentration of the nanoparticles, preferably exposed to or having sound waves or radiation applied thereon, preferably located in a body part or nanoparticle region, is greater than 10. -50 10 -20 10 -10 10 -9 10 -6 10 -3 1, 2, 5, 10, 10 2 10 5 10 10 10 20 Or 10 50 Nanoparticle concentration is measured per cubic centimeter or per cubic centimeter of body fraction, or per gram of nanoparticles. High concentrations of nanoparticles may be required to induce acoustic effects on the nanoparticles, such as temperature increases or the dissociation of compounds from the nanoparticles. In some cases, nanoparticle concentration is the concentration of at least one substance contained within the nanoparticles, such as iron, oxides, iron oxide, or another metal besides iron.

[0237] The present invention also relates to nanoparticles used according to the invention, wherein the concentration of the nanoparticles, preferably exposed to or having sound waves or radiation applied thereon, preferably located in a body part or nanoparticle region, is between 10. -50 and 10 50 10 -20 and 10 20 10 -3 and 10 3 0 and 10 50 1 and 10 100 1 and 10 20 or between 1 and 10 5 Nanoparticles are measured per cubic centimeter or per cubic centimeter of body portion, or grams of nanoparticles are measured per cubic centimeter or per cubic centimeter of body portion.

[0238] In yet another embodiment of the invention, the nanoparticle concentration is contained between a minimum and a maximum value. In some cases, the minimum value is large enough to allow heat to be generated through the nanoparticles or to cause compounds to dissociate from the nanoparticles, preferably under laser radiation. In some other cases, the maximum value is low enough to prevent imaging of body parts.

[0239] The present invention also relates to nanoparticles for use according to the invention, the nanoparticles having or resulting in at least one of the following properties:

[0240] I) Generation of the slope of the initial temperature change over time, which is greater than 10. -9 Or 10 -50 Measured per second based on gram of nanoparticles or per cubic centimeter of body part or gram of nanoparticles per cubic centimeter of body part.

[0241] ii) Specific absorption rate greater than 10 -9 Watts per gram of nanoparticles or watts per cubic centimeter of body part, and / or

[0242] iii) Specific absorptivity increases with increasing acoustic power applied to nanoparticles, and its rate increases with decreasing nanoparticle concentration.

[0243] In some cases, the initial slope of temperature change over time, preferably increasing, can be measured or obtained by applying sound waves to nanoparticles or body parts.

[0244] In some cases, (ΔT / δt) (N) It could be the initial change in temperature over time of a part of the body containing nanoparticles.

[0245] In some cases, (ΔT / δt) (WN) It could be the initial change in temperature over time in body parts that do not contain nanoparticles.

[0246] In some cases, the abbreviation N for nanoparticles can be replaced by the abbreviation M for magnetosomes.

[0247] In some cases, (ΔT / δt) real , (ΔT / δt) (N) , or (ΔT / δt) (WN) This can be expressed as exceeding 1%, 5%, 10%, 50%, 75%, or 10%. 2 Or 10 3 The temperature change, in the initial time of the application of the sound wave or radiation, is expressed in t. i This percentage can be the ratio between the temperature change achieved during ti and the initial temperature immediately before the application of the sound wave or radiation.

[0248] In some cases, (ΔT / δt) real It can be equal to (ΔT / δt) (N) - (ΔT / δt) (WN) .

[0249] In some cases, (ΔT / δt) real , (ΔT / δt) (N) , and / or (ΔT / δt) (WN) It could be the slope of the initial temperature change over time: i) 10 days before the sound wave is applied. -9 10 -6 10 -3 10 -1 , 1, 10, 10 3 Or 10 5 Within minutes, ii) in less than 10 3 10 2 ,10,1,10 -2 10 -3 10 -6 Or 10 -9 Within seconds, preferably after the application of sound waves or radiation, iii) when the temperature changes linearly with time, iv) before the saturation temperature is reached, v) during the initial time of heating or heating step, which represents less than 1, 5, 10, 25, 50, 75, 80, 90, 95, or 99 percent of the total duration of heating or heating.

[0250] In one embodiment of the invention, (ΔT / δt) (N) , (ΔT / δt) (WN) , and / or (ΔT / δt) real The value is greater than 10 -100 10 -50 10 -20 10 -9 10 -7 10 -6 10 -5 10 -3 10 -1 ,1,10 3 10 5 10 6 Or 10 9 Degrees Celsius per second. In some cases, ((ΔT / δt) (N) and / or (ΔT / δt) real Larger power is achieved when nanoparticles have a large heating power, or when the sound waves or radiation applied to nanoparticles have a large power.

[0251] In another embodiment of the invention, ((ΔT / δt)(N) , (ΔT / δt) (WN) , and / or (ΔT / δt) real The value is less than 10 100 10 50 10 20 10 9 10 6 10 3 ,1,10 -1 10 -3 10 -6 Or 10 -9 Degrees Celsius per second. In some cases, ((ΔT / δt) (N) and / or (ΔT / δt) real Smaller is when nanoparticles have lower heating power, or when the sound waves or radiation applied to nanoparticles have lower power.

[0252] In another embodiment of the invention, (ΔT / δt) (N) , (ΔT / δt) (WN) and / or (ΔT / δt) real Between 10 -100 and 10 100 10 -10 and 10 10 10 -5 and 10 5 or between 10 -5 and 10, 10 -5 Celsius per second.

[0253] In some cases, the unit of degrees Celsius per second can be replaced by degrees Celsius per gram of nanoparticles, per gram of body part, per cubic centimeter of nanoparticles, per square centimeter of nanoparticles, per centimeter of nanoparticles, per cubic centimeter of body part, per square centimeter of body part, or per centimeter of body part.

[0254] In one embodiment of the invention, (ΔT / δt) (N) Ratio (ΔT / δt) (WN) Large alpha factor: where α is i) in some cases, greater than 1.00001, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 10 5 Or 10 9 or greater than 10 -100 10 -50 10 -20 10 -9 10 -6 10 -3 10 -1 ,1,10 310 6 Or 10 9 (ii) less than 10 degrees Celsius per second in some other cases. 5 10 3 10 2 5, 2 or 1.1 or less than 10 100 10 50 10 5 10 2 , 5, 2 or 1.5 or iii) in some other cases, including 10 -100 and 10 100 10 -5 and 10 5 10 -1 And 10, or between 10 -100 and 10 100 Celsius per second, or between 10 -10 and 10 5 Celsius per second.

[0255] In one embodiment of the invention, (ΔT / δt) (M) The appropriate range of values ​​is between 0.09 degrees Celsius per second and 0.7 degrees Celsius per second. The minimum value of this range (0.09 degrees Celsius per second) is estimated by exposing 45 micrograms of magnetic particles or nanoparticles per square centimeter of tissue to 0.5 watts per square centimeter of sound waves. In some cases, this minimum value can be greater than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 , or 10 20 The factor is reduced, preferably by increasing the concentration of magnetic particles or nanoparticles to more than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 , or 10 20 The factor is reduced by adjusting the intensity, power, or frequency of the sound wave through 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 , or 10 20 The factor decreases. The minimum value of this range (0.7 degrees Celsius per second) is estimated by exposing 100 micrograms of magnetic particles mixed in 100 microliters of water to a sound wave of 1.5 watts per square centimeter. In some cases, this minimum value can be greater than 1.5, 2, 5, 10, 50, 10 2 10 510 7 10 9 Or 10 20 The factor is increased, preferably by increasing the concentration of magnetosomes or nanoparticles to more than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 The factor is increased by increasing the intensity, power, or frequency of the sound wave by more than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 The factor increases.

[0256] In another embodiment of the invention, (ΔT / δt) (WM) The appropriate value range is between 0.063 degrees Celsius per second and 0.645 degrees Celsius per second. The minimum value in this range (0.063 degrees Celsius per second) is estimated by applying a sound wave of 0.5 watts per square centimeter to a piece of tissue. In some cases, it can be estimated by applying values ​​exceeding 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 , or 10 20 The factor reduces the intensity, power, or frequency of the sound wave to reduce that minimum value by 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 Or 10 20 The factor, the maximum value of which is 0.645 degrees Celsius per second, was estimated by applying a sound wave of 1.5 watts per square centimeter to an aqueous solution. In some cases, it was estimated by applying a sound wave of more than 1.5, 2, 5, 10, 50, 10 watts per square centimeter. 2 10 5 10 7 10 9 , or 10 20 The factor that increases the intensity, power, or frequency of a sound wave can be used to adjust this maximum value through 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 Increase the factor, or use body parts that absorb less sound waves.

[0257] In one embodiment of the invention, the specific absorption rate (SAR) of the nanoparticles, also designated as SAR, is the specific absorption rate of nanoparticles contained, mixed or inserted into the body portion, which can be expressed in power units (e.g., watts) divided by mass units (e.g., grams) or in power units divided by length, surface area or volume units (e.g., centimeters, square centimeters or cubic centimeters).

[0258] Preferably, the specific absorptivity is measured under the influence of sound waves or radiation, which preferably increase the temperature in the presence of nanoparticles. In some cases, such radiation or sound waves may have: i) a power or power density greater than 10 -9 10 -5 10 -3 10 -1 1, 10 or 10 3 Tiles per centimeter, tiles per square centimeter or tiles per cubic centimeter, ii) frequency greater than 10 -6 10 -3 10 -1 , 1, 10, 10 3 Or 10 6 Megahertz. In some other cases, this radiation can be an alternating magnetic field, preferably: i) greater than 10 -9 10 -6 10 -3 ,1,10 3 10 6 Or 10 9 The frequency of kilohertz, and / or ii) greater than 10 -9 10 -6 10 -3 10 -1 , 1, 10, 10 3 Or 10 6 With an intensity of millitalas, and in some other cases, this radiation can be a laser, preferably with a power or power density greater than 10. -9 10 -5 10 -3 10 -1 1, 10 or 10 3 Tiles per centimeter, tiles per square centimeter, or tiles per cubic centimeter.

[0259] Preferably, the SAR measured under adiabatic conditions or under conditions with minimized heat exchange is preferably performed between: i) the nanoparticle-containing portion of a body part and the non-nanoparticle-containing portion of a body part, or the nanoparticle-containing region outside the body part, or ii) the container or test tube containing the nanoparticles and the exterior of the container or test tube. Preferably, heat exchange is minimized when the temperature reduction caused by heat exchange is below 75, 60, 50, 25, 10, 5, 2, 1, or 0.1 degrees Celsius.

[0260] In one embodiment of the invention, the SAR is estimated by exposing nanoparticles, preferably contained in a body part, to sound waves or radiation. In some cases, the SAR may be equal to or proportional to the specific heat capacity of the medium surrounding the nanoparticles, preferably multiplied by the initial slope of the temperature change over time caused by the application of sound waves or radiation, and preferably divided by the nanoparticle concentration.

[0261] In another embodiment of the invention, the SAR does not correspond to, is not related to, or is not the same as the SAR estimated by exposing the nanoparticles to an alternating magnetic field or other excitation sources other than sound waves or radiation.

[0262] The present invention also relates to nanoparticles used according to the invention, wherein the nanoparticles have a measured specific absorption rate (SAR), preferably measured in the body portion, greater than 10. -100 10 -50 10 -20 10 -9 10 -6 10 -3 ,1,10 3 10 6 Or 10 9 Watts (watts) are calculated based on the number of nanoparticles per gram (W / g). nano ), nanoparticles per cubic centimeter (W / cm 3 nano ), per gram of body part (W / g bp ), or per cubic centimeter of body part (W / cm 3 bp The SAR value is measured by [the specific conditions]. In some cases, large SAR values ​​can be obtained under specific conditions, such as using sound waves or high-power or high-frequency radiation, using high nanoparticle concentrations, combining the application of sound waves with the application of another energy source, or combining the application of different types of sound waves or radiation.

[0263] The present invention also relates to nanoparticles used according to the invention, wherein the nanoparticles have a specific absorption rate (SAR), preferably measured in the body portion, below 10. 100 10 50 10 2010 -9 10 -6 10 -3 ,1,10 3 10 6 Or 10 9 W / g nano ), nanoparticles per cubic centimeter (W / cm 3 nano ), per gram of body part (W / g bp ), or per cubic centimeter of body part (W / cm 3 bp ) as measured.

[0264] The present invention also relates to nanoparticles used according to the invention, wherein the nanoparticles have a specific absorption rate (SAR), preferably measured in the body portion, which is between 10. -100 and 10 100 10 -10 and 10 10 10 -5 and 10 5 10 -3 and 10 3 0 and 10 100 10 and 10 10 10 and 10 4 W / g nano ), nanoparticles per cubic centimeter (W / cm 3 nano ), per gram of body part (W / g bp ), or per cubic centimeter of body part (W / cm 3 bp ) as measured.

[0265] In one embodiment of the invention, a suitable range for nanoparticle SAR measured under acoustic applications is preferably between 1.2 W / g nanoparticles, preferably calculated in terms of iron, and 424 W / g nanoparticles, preferably calculated in terms of iron. In some cases, the minimum value of this range (1.2 W / g) is... M It may decrease, for example, by more than 1.5, 2, 5, 10, or 10. 3 10 5 10 7 Or 10 9 The factors are preferably such that when the viscosity of the body part increases or when the thermal diffusion of the body part decreases, or when the diffusion of nanoparticles into the body part increases, or when the power of the sound waves decreases, or when the heat generated by the sound waves increases in the absence of nanoparticles. In some other cases, this range (424 W / g) is preferred. MThe maximum value can be increased, for example, to greater than 1.5, 2, 5, 10, 10. 3 10 5 10 7 Or 10 9 The preferred factors are when the viscosity of the body part decreases, or when the thermal diffusion of the body part increases, or when the concentration of nanoparticles in the body part increases, or when the power of the sound wave increases, or when the heat generated by the sound wave decreases when the nanoparticles are absent.

[0266] In another embodiment of the invention, the minimum value of SAR can be explained by the fact that the SAR value can decrease with decreasing nanoparticle concentration or number, preferably exceeding 1.1, 2, 5, 10, 10. 2 10 3 10 5 Or 10 10 The factor, and preferably, is greater than 1.1, 2, 5, 10, 10. 2 10 3 10 5 Or 10 10 The factor decreases. For example, 10 7 The SAR value of 1 watt per gram of nanoparticles can be used to derive the SAR value of 10 nanoparticles. -7 The SAR value per watt per gram of nanoparticles. This behavior can be explained by a collective effect, where the SAR values ​​of individual nanoparticles are superimposed to produce the SAR used for nanoparticle assembly, which is the sum of or proportional to the SAR values ​​of the individual nanoparticles. In another embodiment of the invention, small nanoparticles with sizes less than 500, 200, 100, 50, 20, 10, or 1 nanometer do not have SAR, or have SAR less than 10. 5 10 3 ,10,1,10 -1 10 -3 10 -6 Or 10 -9 Watts per gram of nanoparticles.

[0267] In another embodiment of the invention, the nanoparticles are preferably large nanoparticles with a size greater than 1, 10, 20, 50, 100, 200, or 500 nanometers, and preferably have an SAR greater than 10. -9 10 -6 10 -3 10 -1 , 1, 10, 10 3 Or 10 5 Watts per gram of nanoparticles.

[0268] The present invention also relates to nanoparticles used according to the invention, wherein the nanoparticles have a specific absorption rate that increases with increasing power of the sound wave applied to the nanoparticles, and whose rate increases with decreasing nanoparticle concentration.

[0269] In some cases, SAR can be increased, preferably exceeding 1.01, 1.1, 2, 5, 10, 10. 2 10 3 10 5 Or 10 10 The factor, when the power of the sound waves or radiation applied to nanoparticles increases, is preferably greater than or equal to 1.1, 2, 5, 10, 10. 2 10 3 10 5 Or 10 10 The preferred rate factor is greater than 1.01, 1.1, 2, 5, 10, 10. 2 10 3 10 5 Or 10 10 The factor increases when the concentration of nanoparticles decreases, preferably exceeding 1.01, 1.1, 2, 5, 10, 10. 2 10 3 10 5 Or 10 10 The factor. To satisfy this characteristic, the nanoparticle concentration should preferably be included in 10. -9 and 10 9 10 -5 and 10 5 10 -2 and 10 2 or between 10 -1 And 10 mg of nanoparticles per milliliter or per cubic centimeter of body portion.

[0270] In one embodiment of the invention, the rate at which SAR increases with increasing intensity of sound waves or radiation corresponds to a percentage increase in SAR, i.e. (SAR...) I2 -SAR I1 ) / SAR I1 SAR I1 and SAR I2 It is a SAR measured at two different intensities of sound waves or radiation I1 and I2, where I2>I1, preferably divided by I2 / I1.

[0271] In another embodiment of the invention, the SAR of the nanoparticles does not change or decrease by more than 10 percent between different nanoparticle concentrations. 5500, 90, 70, 50, 25, 10, 5, or 2, where the percentage can be expressed as C2-C1 / C1, where C1 and C2 are two different nanoparticle concentrations. In some cases, this occurs when the nanoparticle concentration is between 10... 6 and 10 6 10 -5 and 10 5 10 -3 and 10 3 or between 10 -2 and 10 2 When the concentration of nanoparticles is between 1000, 100, 10, 1, 0.1, or 0.01 mg / mL or 100 mg / cm³ body portion. In some other cases, this occurs when the concentration of nanoparticles is greater than 000, 100, 10, 1, 0.1, or 0.01 mg / mL or 100 mg / cm³ body portion.

[0272] In one embodiment of the invention, the nanoparticles have a specific absorption rate that increases as the nanoparticle concentration decreases. In some cases, the specific absorption rate increases when the nanoparticle concentration decreases by 1.1, 2, 5, 10, or 10 times. 2 10 3 10 5 Or 10 10 When the factor is [value missing], the absorption rate of nanoparticles will increase by more than 1.1, 2, 5, 10, 10 [value missing]. 2 10 3 10 5 Or 10 10 The factor. To satisfy this characteristic, the nanoparticle concentration should preferably be between 10. -9 and 10 9 10 -5 and 10 5 10 -2 and 10 2 or between 10 -1 The concentration should be between 10 mg / mL and 10 mg / mL, or the nanoparticle concentration should be below 10 mg / mL. -9 10 -7 10 -5 10 -2 10 -1 1, 10, or 100 mg of nanoparticles per milliliter. This behavior is interesting because it is the opposite of what is observed when SAR is measured by applying an alternating magnetic field.

[0273] In some cases, SAR can be specified as (SAR). (real)。 )

[0274] In some cases, the initial slope of the body part's temperature change with or without nanoparticles is considered, (SAR) (real)。 It can be the specific absorption rate of nanoparticles.

[0275] In one embodiment of the invention, the rate of increase of SAR with increasing acoustic power falls within a suitable range of 15% to 440%. The minimum and maximum values ​​of this range are given in Tables 2 and 1, respectively, using SAR... real The value of (M) is used for estimation. In some cases, the minimum value of this range can be estimated by reducing the intensity of the sound wave or by changing the maximum concentration or body part, preferably by reducing it by more than 2, 5, 10, or 10. 3 Or 10 5 The factor. In some other cases, the maximum value of this range can be, preferably greater than 2, 5, 10, or 10, by increasing the intensity of the sound wave or by changing the maximum concentration or body part. 3 Or 10 5 The factor increases.

[0276] In some cases, SAR (real) The formula can be used: To estimate, where α real It is a proportionality constant, which can be equal to C. v / C nano , where C v It is the specific heat capacity, preferably for body parts, tissues, water, and media containing nanoparticles, C nano Preferably, it refers to the concentration, total amount, or number of nanoparticles in the body part.

[0277] In another embodiment of the invention, SAR (real) The appropriate range for the value is between 5 watts per gram and 427 watts per gram. The minimum value of 5 watts per gram is estimated by applying a sound wave of 1 watt per square centimeter to 45 micrograms of magnetic particles per square centimeter of tissue. In some cases, this is achieved by reducing the intensity, power, or frequency of the sound wave by 1.5, 2, 5, 10, 50, or 10. 2 10 5 10 7 10 9 Or 10 20 The minimum value can be reduced by factors greater than 1.5, 2, 5, 10, 50, and 10. 2 10 5 10 7 10 9 Or 10 20The factor. The maximum value of this range, 427 watts per gram, is estimated by applying a sound wave of 1 watt per square centimeter to an aqueous solution containing 100 microliters of water mixed with 100 micrograms of magnetic particles. In some cases, this is achieved by increasing the intensity, power, or frequency of the sound wave by more than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 The factor, the maximum value can be increased to greater than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 Or 10 20 Factors that absorb sound waves, or by using body parts that absorb less sound waves.

[0278] In some other cases, SAR can be equal to SAR(N).

[0279] In some cases, SAR (N) =α N (ΔT / δt) (N) , where α N It can be equal to C v / C mag .

[0280] In another embodiment of the invention, SAR (N) The appropriate range for the value is between 37 watts per gram and 3124 watts per gram. The minimum value of 37 watts per gram is estimated by applying a sound wave of 1 watt per square centimeter to 45 micrograms of magnetic particles per square centimeter of tissue. In some cases, this is achieved by reducing the intensity, power, or frequency of the sound wave by 1.5, 2, 5, 10, 50, or 10. 2 10 5 10 7 10 9 , or 10 20 The factor, the minimum value can be reduced by more than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 , or 10 20 The factor. The maximum value of this range, 3124 watts per gram, is estimated by applying a sound wave of 1.5 watts per square centimeter to an aqueous solution containing a mixture of 100 microliters of water and 100 micrograms of magnetic particles. In some cases, this is achieved by increasing the intensity, power, or frequency of the sound wave by more than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 710 9 Or 10 20 The factor, the maximum value can be increased beyond 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 Factors that absorb sound waves, or by using body parts that absorb less sound waves.

[0281] In another embodiment of the invention, α N and / or α WN The value is less than 10 -9 10 -6 10 -3 ,1,10 3 10 6 Or 10 9 (seconds per degree Celsius) (watts per gram of nanoparticles) or (seconds per degree Celsius) (watts per gram of body part) or (seconds per degree Celsius) (watts per cubic centimeter of nanoparticles).

[0282] In another embodiment of the invention, α N and / or α WN The value is greater than 10 -9 10 -6 10 -3 ,1,10 3 10 6 Or 10 9 (seconds per degree Celsius) (watts per gram of nanoparticles) or (seconds per degree Celsius) (watts per gram of body part) or (seconds per degree Celsius) (watts per cubic centimeter of nanoparticles).

[0283] In some other cases, SAR can be equal to SAR AW SAR AW SAR is a measurement method that applies acoustic waves to nanoparticles. AW Unlike SAR, which is measured by applying an alternating magnetic field, SAR can be used... AM In other words, SAR. AW With SAR AMF The difference is at least 10%. -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 Or 10 9 This percentage can be equal to (SAR) AW -SARAMF ) / SAR AW The percentage is preferably determined for a given concentration of nanoparticles, preferably: i) in some cases, less than 10 9 10 7 10 5 10 3 ,10,1,10 -3 10 -5 10 -7 Or 10 -9 Milligram nanoparticles are measured per cubic centimeter or cubic centimeter of body portion, ii) in some other cases, greater than 10. -9 10 -7 10 -5 10 -3 10 -1 ,1,10 3 10 5 10 7 Or 10 9 Milligram nanoparticles are measured per cubic centimeter or cubic centimeter of body portion, or (iii) in some other cases, contained in between 10 -9 and 10 9 10 -7 and 10 7 10 -5 and 10 5 10 -3 and 10 3 or between 10 -1 And 10 milligrams of nanoparticles, measured per cubic centimeter or cubic centimeter of body part.

[0284] In one embodiment of the invention, SAR is not measured in the presence of a magnetic field or alternating magnetic field applied to the nanoparticles. In some cases, SAR is preferably not attributed to hysteresis loss, Brownian motion, Nell relaxation, or the motion of the nanoparticles under the influence of sound waves, nor to the reversal of the magnetic moment of the nanoparticles under the influence of sound waves, or the coupling of the magnetic moment of the nanoparticles with the sound waves.

[0285] In another embodiment of the invention, SAR AW It is not, or not only, or primarily not due to Brownian motion, Nell relaxation, or hysteresis losses. In some cases, SAR AW This is primarily attributed to the absorption of sound waves by nanoparticles, either partially or primarily, or by the body portion containing nanoparticles. In some cases, SAR AWThis is attributed to the fact that, preferably partially or primarily, body parts that do not contain or do not contain nanoparticles absorb sound waves, preferably followed by thermal diffusion between body parts that do not contain or do not contain nanoparticles and body parts that contain or have nanoparticles.

[0286] In one embodiment of the invention, the portion of the body part comprising nanoparticles is a nanoparticle region or nanoparticle, and the nanoparticle composition or nanoparticle suspension is or has been applied.

[0287] In another embodiment of the invention, the body portion without nanoparticles is the portion where nanoparticles, nanoparticle components, or nanoparticle suspensions are absent or have not yet been applied, such as portions of the body portion before nanoparticle application or outside the nanoparticle region.

[0288] In some cases, parts of the body containing nanoparticles can absorb more than 10%. -9 10 -7 10 -5 10 -3 10 -1 The energy of sound waves or radiation of 1, 5, 10, 25, 50, 75, or 80, excluding the body portion of nanoparticles, can preferably be absorbed by less than 10%. -9 10 -7 10 -5 10 -3 10 -1 The energy of sound waves or radiation is 1, 5, 10, 25, 50, 75, or 80. In some other cases, body parts containing nanoparticles can absorb less than 10%. -9 10 -7 10 -5 10 -3 10 -1 Sound wave or radiation energy of 1, 5, 10, 25, 50, 75 or 80, excluding the body portion containing nanoparticles, can preferably be absorbed by more than 10%. -9 10 -7 10 -5 10 -3 10 -1 The energy of the sound waves or radiation is 1, 5, 10, 25, 50, 75, or 80. The percentages mentioned in this embodiment and previous embodiments may represent or apply the energy of the sound waves or radiation on the nanoparticles divided by the energy of the sound waves or radiation applied to the body part, or the energy of the sound waves or radiation applied to the nanoparticles or body part divided by the energy of the sound waves or radiation generated by the device that generates the sound waves or radiation.

[0289] In some cases, "body part" can refer to a portion of a body or a part of a body that contains nanoparticles.

[0290] In some other cases, a body part may be specified as a portion of the body or a portion of the body that does not include nanoparticles.

[0291] In some other cases, a body part can be specified as either a portion of the body part that includes nanoparticles or nanoparticle regions, or a portion of the body part that does not include nanoparticles or nanoparticle regions.

[0292] In some cases, body parts may include: i) more than 10 -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 Or 10 9 Milligram nanoparticles, preferably per cubic millimeter or per cubic centimeter of body portion or per pathological or healthy cell, or ii) more than 10 -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 o or 10 9 Each pathological or healthy cell, preferably per cubic millimeter or per cubic centimeter of body portion.

[0293] In some other cases, body parts may include: i) fewer than 10 -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 Or 10 9 Milligram nanoparticles, preferably per cubic millimeter or per cubic centimeter of body portion or per pathological or healthy cell, or ii) less than 10 -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 o or 10 9Each pathological or healthy cell, preferably per cubic millimeter or per cubic centimeter of body portion.

[0294] The present invention also relates to nanoparticles used according to the invention, wherein the concentration of the applied nanoparticles is greater than 10 in some cases. -3 Milligrams per cubic millimeter of body tissue. In some cases, the concentration of nanoparticles is greater than 10. -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 Or 10 9 Grams or milligrams per cubic millimeter of body part, per milliliter of suspension, or per milliliter of matrix or body part (biological or non-biological) containing nanoparticles.

[0295] In one embodiment of the invention, a suitable range for the concentration of nanoparticles contained in the body portion is between 1 nanogram of nanoparticles, preferably in iron, per cubic millimeter of body portion and 1 gram of nanoparticles, preferably in iron, per cubic millimeter of body portion. The minimum of this range (1 nanogram per cubic millimeter) can be estimated by calculating the lowest concentration of the magnetic particle or nanoparticle suspension applied to the body portion, i.e., the lowest detectable concentration of magnetic particles or nanoparticles. In some cases, this minimum may be reduced, for example, by more than 10-10. 3 10 6 Or 10 9 The factor is determined if a more sensitive detection method is used or developed to detect the presence of magnetosomes or nanoparticles, or if a portion of the magnetosomes or nanoparticles diffuse away from the body site after administration. The maximum value of this range (1 gram per cubic millimeter) can be estimated by calculating the maximum concentration of magnetosomes or nanoparticles that produces a stable suspension. For example, if the magnetosomes or nanoparticles are inserted into a solid, semi-solid, or more viscous matrix or solvent than water, this maximum value may be larger, for example, increasing by 10, 10, 10 3 10 6 Or 10 9 Multiples. Or, if the magnetosomes concentrate in the body after administration, the concentration produced in the body will be greater than the concentration in the injectable magneticosome or nanoparticle suspension.

[0296] In another embodiment of the invention, the nanoparticles are retained in the body portion during treatment, preferably in quantities exceeding 1, 2, 5, 10, 20, 50, 100, or 10. 3 Or 10 4In sequences or courses of treatment, it is preferred to have more than 1, 2, 5, 10, 50, 100 or 10 3 Within a day.

[0297] In another embodiment of the invention, the nanoparticles are retained in the body portion during treatment, preferably in quantities of less than 1, 2, 5, 10, 20, 50, 100, or 10. 3 Or 10 4 In a sequence or course of treatment, preferably less than 1, 2, 5, 10, 50, 100 or 10 3 Within a day.

[0298] In some cases, the nanoparticles remain in the body during the treatment without shrinking in size by more than 10 percent. -4 10 -1 1, 10, 20, 50, 100, 500, 10 3 Or 10 4 In some cases, this percentage can be equal to the ratio between the size of the nanoparticles after administration to the size of the nanoparticles before administration to the body.

[0299] In some cases, body parts are those exposed to radiation or sound waves.

[0300] In this invention, body parts or nanoparticles exposed to sound waves or radiation can represent sound wave or radiation coverage, targets, presences, application therein, or locations thereof. Preferably, they constitute at least 10 percent of the body parts or nanoparticles. -9 10 -7 10 -5 10 -3 10 -1 1, 5, 10, 25, 50, 75, or 80. This percentage can represent the number or volume of nanoparticles or body parts exposed to sound waves or radiation divided by the total number or volume of nanoparticles or body parts. In some cases, sound waves or radiation may also cover, target, be present, be applied to or located outside of body parts or nanoparticles, preferably when such sound waves or radiation have sufficiently low power or energy to avoid causing toxicity.

[0301] Furthermore, in certain situations, when sound waves or radiation are applied to body parts or nanoparticles, or when sound waves or radiation are applied to body parts or nanoparticles, the body parts or nanoparticles may be exposed to sound waves or radiation. This exposure occurs when body parts or nanoparticles are subjected to sound waves or radiation, or when body parts or nanoparticles are subjected to the effects of sound waves or radiation, or when body parts or nanoparticles are subjected to interference caused by sound waves or radiation.

[0302] In one embodiment of the invention, the body part is associated with or related to: i) a body part exposed to sound waves or radiation, or ii) a body part receiving energy or power from sound waves or radiation, or iii) a body part absorbing energy or power from sound waves or radiation.

[0303] In some cases, a body part may also be associated with or related to the following substances: i) the body part is not exposed to sound waves or radiation; or ii) the body part does not receive the energy or power of sound waves or radiation; or iii) the body part does not absorb the energy or power of sound waves or radiation.

[0304] The present invention also relates to nanoparticles for use according to the invention, wherein the application of sound waves or radiation to a body part causes an increase in the temperature of the body part, preferably greater than 10°C. -10 10 -5 10 -3 10 -1 1, 5, 10 or 10 3 Celsius.

[0305] In some cases, the temperature rise is at least 10 percent higher when nanoparticles are not present in parts of the body compared to when nanoparticles are not present in parts of the body. -10 10 -5 10 -1 1, 2, 5, 10, 50, 75, or 80. In some cases, this percentage can be the ratio between the temperature increase of the body portion where nanoparticles are absent and the temperature increase of the body portion where nanoparticles are present. The invention also relates to nanoparticles used according to the invention, wherein an increase in body portion temperature, a decrease in body portion temperature, or dissociation of compounds in the nanoparticles occurs in less than 10 percent. 20 10 10 10 5 10 3 500, 200, 90, 70, 50, 10, or 1% of the body portion. This percentage can be the ratio between the increase in body portion temperature, the decrease in body portion temperature, or the ratio between the volume of the compound dissociating from the nanoparticles and the total volume of the body portion.

[0306] In other cases, an increase in body part temperature, a decrease in body part temperature, or dissociation of the compound from the nanoparticles can occur in more than 10 percent of cases. -10 10 -5 10 -1 1, 10, 50, 70, 90, 200, 500, 10 3 10 5 Or 1020 Within the body parts.

[0307] The present invention also relates to nanoparticles used according to the invention, wherein an increase in the temperature of the body part, a decrease in the temperature of the body part, or the dissociation of the compound from the nanoparticles occurs in a volume greater than 10 percent of the body part occupied by the nanoparticles. -10 10 -5 10 -1 1, 10, 50, 70, 90, 200, 500, 10 3 10 5 10 10 Or 10 20 Within. This percentage can be the ratio between the increase in body part temperature, the decrease in body part temperature, or the volume of the compound dissociating from the nanoparticles to the total volume of the body part.

[0308] In some other cases, an increase in body part temperature, a decrease in body part temperature, or the dissociation of compounds from nanoparticles can occur in areas where the nanoparticles occupy less than 10% of the body part volume. 20 10 10 10 5 10 3 500, 200, 90, 70, 50%, 10% or within 1%.

[0309] In embodiments of the invention, the body part comprises more than or at least 1, 2, 5, 10, or 100 similar or different organisms, devices, organs, tissues, cells, or biomolecules. In some cases, the body part may be all or part of the head, neck, shoulder, arm, leg, knee, foot, hand, ankle, elbow, torso, lower or upper member. In some other cases, a body part can be or belongs to an organ, musculoskeletal system, muscle, digestive system, respiratory system, urinary system, female reproductive system, male reproductive system, circulatory system, cardiovascular system, endocrine system, lymphatic system, nerves (peripheral or non-peripheral), ventricles, enteric nervous system, sensory or integrative system, reproductive organs (internal or external), sensory organs, endocrine glands. The organs or body parts described can be the human skeleton, joints, ligaments, tendons, mouth, teeth, tongue, salivary glands, sublingual glands, pharynx, esophagus, stomach, small intestine, duodenum, jejunum, ileum, large intestine, liver, gallbladder, mesentery, pancreas, nasal cavity, pharynx, larynx, trachea, bronchi, lungs, diaphragm, kidneys, ureters, bladder, urethra, ovary. Fallopian tubes, uterus, vagina, vulva, clitoris, placenta, testes, epididymis, vas deferens, seminal vesicles, prostate, urethral glands, penis, scrotum, pituitary gland, pineal gland, thyroid gland, parathyroid glands, adrenal glands, pancreas, heart, arteries, veins, capillaries, lymphatic vessels, lymph nodes, bone marrow, thymus, spleen, enteroassociated lymphoid tissue, tonsils, brain, cerebrum, cerebral hemispheres, diencephalon, brainstem, midbrain, cerebellum, spinal cord, choroid plexus, nerves, cranial nerves, spinal nerves, ganglia, eyes, cornea, iris, ciliary body, lens, retina, ear, outer ear, earlobe, tympanic membrane, middle ear, joints, inner ear, cochlea, vestibule of the ear, semicircular canal, olfactory epithelium, tongue, taste buds, mammary glands, or skin. Body parts or organs may belong to the circulatory system or blood circulation.

[0310] In some cases, a body part may be or include at least one tumor, cancer, virus, bacteria, or pathological cell.

[0311] In one embodiment of the invention, the body part is or contains water, excipients, solutions, suspensions, at least one chemical element, organic material, or gel that can be synthesized or produced by a living organism.

[0312] Preferably, the body part of an individual, also designated as a body part, represents or is part of an individual or the whole individual, wherein the individual is preferably a human, animal or organism, preferably a living or inactive or dead organism, including at least one prokaryotic or eukaryotic cell.

[0313] In one embodiment of the invention, the body part is alive (or not), and is any tissue, water, medium, substance, cell, organelle, organ protein, lipid, DNA, RNA, or biological material, preferably located in a specific region of the individual, preferably originating from or extracted from that region.

[0314] In one embodiment of the invention, the body portion includes a lesion site, a healthy site, and / or a nanoparticle region.

[0315] In one embodiment of the invention, the body part is or includes a pathological site or pathological cells.

[0316] In some cases, a pathological site can be defined as an unhealthy site, or a site in a different condition from that of a healthy individual or an unhealthy individual. It can contain pathological cells, such as tumor cells, bacteria, eukaryotic or prokaryotic cells, as well as viruses or other pathological material. Pathological cells can be i) not arranged or functioning normally as in a healthy individual, ii) dividing faster than healthy cells, iii) healthy cells that have undergone transformation or modification, iv) dead, sometimes due to the presence of viruses or other organisms, or v) interacting in contact. In some cases, viruses may penetrate, colonize, or replicate in these cells. In some cases, pathological cells may assimilate with viruses or other organisms or entities that may colonize or target cells, or destroy or use cells or interact with cells, thereby preferably enabling them to replicate, multiply, survive, or die. In some cases, a pathological site may include healthy cells, preferably with a lower number and reproductive activity compared to pathological cells.

[0317] In one embodiment of the invention, a body part is or includes a healthy site or healthy cells. In some cases, a healthy region can be defined as a site or region comprising healthy cells, wherein a healthy cell can be defined as a cell belonging to a healthy individual or a body part of a healthy individual.

[0318] In some cases, the healthy part may surround the pathological part when its distance from the pathological part is less than 1,10. -1 10 -3 10 -6 Or 10 -9 Rice time.

[0319] In some cases, the number of pathological or healthy cells, preferably included in the body part or volume exposed to sound waves or radiation, may be less than 10. 100 10 50 10 20 10 10 10 5 10, 5, 2 or 1 cells, preferably per square centimeter of body part.

[0320] In some other cases, the number of pathological or healthy cells, preferably included in the body part or volume exposed to sound waves or radiation, may be greater than 1, 10, or 10-1.3 10 5 10 7 10 9 10 20 10 50 Or 10 100 Cells, preferably per square centimeter of body part.

[0321] In some other cases, the ratio between the number of pathological cells and the number of healthy cells, preferably contained in the body part or volume exposed to sound waves or radiation, may be less than 10. 100 10 50 10 20 10 10 10 5 10 3 10 2 , 10, 5, 2 or 1.

[0322] In several other cases, the ratio between the number of pathological cells and the number of healthy cells, preferably contained in the body part or volume exposed to sound waves or radiation, may be greater than 1, 2, 5, 10, or 10. 3 10 5 10 20 Or 10 100 .

[0323] In another embodiment of the invention, the body portion, healthy or pathological site, or nanoparticle region has a density greater than 10. 3 ,1,10 -1 10 -2 10 -3 10 -4 10 -5 10 -6 10 -7 10 -8 , or 10 -9 Or 10 -20 Measured by length, surface area, or volume respectively.

[0324] In another embodiment of the invention, the body portion, healthy or pathological site, or nanoparticle region has a density of less than 1,10. -1 10 -2 10 -3 10 -4 10 -5 10 -6 Or 10 -9 Measured by length, surface area, or volume respectively.

[0325] In one embodiment of the invention, the nanoparticles are applied to or into a body part, either directly to the body part or when applied near the body part, preferably less than 1,100 cm from the body part. -1 10 -2 10 -3 10 -4 10 -5 10 -6 Or 10 -9 In this case, nanoparticles may not need to be transported or diffused from the area where they are applied to the body part.

[0326] In another embodiment of the invention, the nanoparticles are applied to or into a body part, preferably at a distance greater than 1,100 cm from the body part when applied away from it. -1 10 -2 10 -3 10 -4 10 -5 10 -6 Or 10 -9 Meters. In this case, nanoparticles may be transported or diffused from the area where they are applied to the body part.

[0327] In another embodiment of the invention, the nanoparticles are applied to or into a body part when they are injected into, mixed with, or introduced into a body part.

[0328] In another embodiment of the invention, the nanoparticles are applied to or into a body part, where the nanoparticles occupy more than 10% of the body portion. -9 10 -7 10 -5 10 -3 1, 10, 25, 50, or 75% of the body portion, where the percentage can be the ratio between the volume of the area occupied by the nanoparticles in the body portion or nanoparticle region and the volume of the body portion, the occupation corresponding to 10% after the nanoparticles are applied. -5 10 -3 10 -1 , 1, 10, 10 3 Or 10 5 Measured in minutes.

[0329] In another embodiment of the invention, the nanoparticles are administered to or into a body part after at least one of the following routes of administration: local, enteric, gastrointestinal, parenteral, local, oral, inhalation, intramuscular, subcutaneous, intratumoral, organ, intravenous, arterial, blood, or tissue.

[0330] In one embodiment of the invention, the thermal conductivity or density of the body portion, the velocity of the sound wave, the attenuation of the sound wave, the absorption of the sound wave, the elasticity of the sound wave, or the acoustic impedance of the sound wave are at least 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 50, 10 greater in the body portion containing nanoparticles than in the body portion without nanoparticles. 2 10 3 Or 10 5 .

[0331] In one embodiment of the invention, the thermal conductivity or density of the body portion, the velocity of the sound wave, the attenuation of the sound wave, the absorption of the sound wave, the elasticity of the sound wave, or the acoustic impedance of the sound wave are at least 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 50, 10 lower in the body portion containing nanoparticles than in the body portion without nanoparticles. 2 10 3 Or 10 5 .

[0332] In one embodiment of the invention, the thermal conductivity of the body portion is at least 10% greater in the body portion containing nanoparticles than in the body portion without nanoparticles. 20 10 10 10 5 10 3 10 2 50, 10, 5, 2, 1, 10 -1 10 -2 10 -3 10 -5 10 -10 Or 10 -20 Vamemir Kelvin.

[0333] In one embodiment of the invention, the thermal conductivity of the body portion is at least 10% lower in the body portion containing nanoparticles than in the body portion without nanoparticles. 20 10 10 10 5 10 3 10 2 50, 10, 5, 2, 1, 10 -1 10 -2 10 -3 10 -5 10 -10 Or 10 -20 Vamemir Kelvin.

[0334] In one embodiment of the invention, the density of the body portion is at least 10 times greater in the body portion containing nanoparticles than in the body portion without nanoparticles.-9 10 -6 10 -3 10 -1 1, 2, 5, 10, 10 3 Or 10 6 grams per cubic centimeter.

[0335] In one embodiment of the invention, the density of the body portion is at least 10% lower in the body portion containing nanoparticles than in the body portion without nanoparticles. -9 10 -6 10 -3 10 -1 1, 2, 5, 10, 10 3 Or 10 6 grams per cubic centimeter.

[0336] In one embodiment of the invention, the speed of sound waves is at least 10 times greater in the body portion containing nanoparticles than in the body portion without nanoparticles. -5 10 -3 10 -1 1, 10, 100, 1000, 1500, 2000, 3000, 5000, 10 4 Or 10 6 meters per second.

[0337] In one embodiment of the invention, the speed of sound waves is at least 10% lower in the body portion containing nanoparticles than in the body portion without nanoparticles. -5 10 -3 10 -1 1, 10, 100, 1000, 1500, 2000, 3000, 5000, 10 4 Or 10 6 meters per second.

[0338] In one embodiment of the invention, the attenuation of sound waves is at least 10% greater in the body portion containing nanoparticles than in the body portion without nanoparticles. -5 10 -3 10 -1 1, 10, 100, 10 3 Or 10 5 dB / cm.

[0339] In one embodiment of the invention, the attenuation of sound waves is at least 10% smaller in the body portion containing nanoparticles than in the body portion without nanoparticles. -5 10 -3 10 -1 1, 10, 100, 10 3 Or 105 dB / cm.

[0340] In one embodiment of the invention, the acoustic impedance of the sound wave is at least 10 greater in the body portion containing nanoparticles than in the body portion without nanoparticles. -3 10 -2 10 -1 0.5, 1, 1.5, 2, 5, 10, 10 2 10 4 10 6 10 9 Or 10 20 MRayl or Kg.m -2 s -1 .

[0341] In one embodiment of the invention, the acoustic impedance of the sound wave is at least 10% smaller in the body portion containing nanoparticles than in the body portion without nanoparticles. -3 10 -2 10 -1 0.5, 1, 1.5, 2, 5, 10, 10 2 10 4 10 6 10 9 or10 20 MRayl or Kg.m -2 s -1 .

[0342] In another embodiment of the invention, between a body portion without nanoparticles and a body portion containing nanoparticles, an increase, decrease, or change in the thermal conductivity or density of the body portion, the velocity of sound waves, the attenuation of sound waves, the absorption of sound waves, the elasticity of sound waves, or the impedance of sound waves is attributed to at least one of the following properties: i) the concentration of nanoparticles in the body portion is greater than 10. -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 Or 10 9 (ii) Nanoparticle size greater than 10 mg / m³ or per cubic centimeter of body part. -6 10 -3 10 -1 1, 20, 50, 10 3 Or 10 6 iii) Nanoparticles are arranged in chains, or iv) Nanoparticles form aggregates.

[0343] In another embodiment of the invention, between a body portion without nanoparticles and a body portion containing nanoparticles, an increase, decrease, or change in the thermal conductivity or density of the body portion, the velocity of sound waves, the attenuation of sound waves, the absorption of sound waves, the elasticity of sound waves, or the impedance of sound waves is attributed to at least one of the following properties: i) the nanoparticle concentration of the body portion is less than 10. -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 Or 10 9 (ii) Nanoparticle size less than 10 mg / m³ or per cubic centimeter of body part. -6 10 -3 10 -1 1, 20, 50, 10 3 Or 10 6 nanometer.

[0344] In one embodiment of the invention, sound wave medical therapy is a medical treatment, and is also specified as medical treatment or therapy.

[0345] In some cases, the treatment uses or is caused by the energy, intensity, or power of sound waves, preferably applied to nanoparticles or body parts. In some cases, the treatment may involve or be caused by sound waves, preferably applied to nanoparticles. In some cases, the treatment triggers medical, pharmaceutical, immune, metabolic, diagnostic, medical device, biological, or cosmetic effects. In some cases, medical treatment can be the treatment of a disease, such as an infectious disease, cancer, or therapeutic treatment. It can be the treatment of a disease caused by an abnormality in the function of an organ or body organ. This may be caused by a malfunction in a part of an individual's body. In some cases, it can be a diagnostic or cosmetic treatment for a disease. In some cases, it can induce at least 1, 10, 10 3 10 6 , or 10 9 The death, destruction, denaturation, or inactivation of biological materials, such as cells, preferably pathological cells, RNA, DNA, proteins, lipids, or enzymes. Cell death may occur via apoptosis or necrosis (preferably apoptosis).

[0346] The present invention also relates to nanoparticles used according to the invention, wherein medical treatment is the treatment of a disease or condition selected from the group consisting of: diseases related to cell proliferation that differs from cell proliferation in a healthy individual, diseases related to the presence of pathological cells in a body part, diseases related to the presence of pathological sites in an individual or body part, diseases or disorders or functional abnormalities of body parts, diseases related to the presence of radiation-resistant or sound-resistant cells, infectious diseases, autoimmune diseases, neuropathology, cancer, tumors, or diseases caused by at least one type of cancer or tumor cell, skin diseases, endocrine disorders, eye diseases or diseases, intestinal diseases, communication disorders, genetic diseases, nervous system diseases, voice disorders, vulvovaginal diseases, liver diseases, heart diseases, febrile diseases, mood disorders, anemia, iron anemia, and personality disorders.

[0347] In some cases, the disease or condition may be a disease or condition of an individual or part of a body or belonging to an individual or part of a body, or a disease or condition that an individual suffers from.

[0348] In one embodiment of the present invention, the cancer or tumor is selected from: organ cancer, hematologic cancer, systemic cancer, adrenal cancer, anal cancer, bile duct cancer, bladder cancer, bone cancer, brain cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, eye cancer, gallbladder cancer, heart cancer, kidney cancer, laryngeal and hypopharyngeal cancer, leukemia, liver cancer, lung cancer, nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-Hodgkin's lymphoma, oral and oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, etc. Adenocarcinoma of the penis, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcoma, skin cancer, small intestine cancer, stomach cancer, testicular cancer, thymic cancer, thyroid cancer, uterine cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenstone macroglobulinemia, infectious tumors, Castle man disease, Ewing family tumors, gastrointestinal carcinoids, gastric cancer, intestinal stromal tumors, myelodysplastic syndrome, pituitary tumors and cancerous diseases such as gestational trophoblastic disease, Hodgkin's disease, Kaposi's sarcoma, malignant mesothelioma and multiple myeloma.

[0349] In one implementation, the dysregulation or dysfunction of a body part is related to cellular dysfunction, such as faster division or entering a state of apoptosis or necrosis, or to dysfunction of the immune system or immune cells.

[0350] In one embodiment of the invention, the medical treatment is or includes the detection or diagnosis of a disease such as those mentioned in the foregoing embodiments.

[0351] In one embodiment of the invention, the medical treatment is for treating anemia, or the nanoparticles are used to treat anemia. Preferably, the anemia is anemia of iron, which is a substance contained in a body part or compound, or a substance contained in the core and / or coating of the nanoparticles. In some cases, anemia can be defined as the concentration of a substance contained in an individual that is 1.001, 1.01, 1.1, 2, 5, 10, 10 lower in an anemic individual than in a healthy individual. 2 10 5 10 10 Or 10 20 times.

[0352] In some cases, anemia in a body part is defined as a lower concentration of a substance (e.g., iron or oxide) contained in nanoparticles or compounds, preferably 1.001, 1.01, 1.1, 2, 5, 10, 10 lower than the concentration after the application or use of nanoparticles before or after the application of nanoparticles to the body part. 2 10 5 10 10 Or 10 20 times.

[0353] The present invention also relates to a method for treating anemia or anemia-related diseases, or to nanoparticles, particularly magnetosomes, for treating anemia-related diseases, preferably iron-related anemia, wherein the magnetosomes are applied to a part of an individual's body, preferably to reduce or stop anemia.

[0354] This invention also relates to a method for treating anemia, wherein the anemia is selected from: iron deficiency anemia, vitamin deficiency anemia, anemia of chronic disease, aplastic anemia, anemia associated with bone marrow disease, hemolytic anemia, sickle cell anemia, thalassemia, pernicious anemia, Fanconi anemia, sideroblastic anemia, congenital erythropoietinemia (CDA), diamond-Black Fan anemia, and megaloblastic anemia. In some cases, anemia is a reduction in the total number of red blood cells (RBCs) or hemoglobin in the blood, or a decrease in the blood's ability to carry oxygen.

[0355] This invention also relates to a method for treating anemia or anemia-related disorders, wherein the treatment is due to, or related to, or caused by, the release or dissociation of iron or free iron from nanoparticles, particularly magnetosomes. In some cases, the percentage of iron released from the nanoparticles (particularly magnetosomes) is greater than 10 percent. -5 10 -3 10 -11, 5, 10, 50, 75, 90, or 99%. In some other cases, the percentage of iron released by nanoparticles, especially magnetosomes, is less than 100%, 99%, 90%, 75%, 50%, 10%, 5%, 1%, or 1%. In some cases, this percentage can be a ratio Q. FI / Q IM Q FI It is the amount of free iron released by nanoparticles, especially magnetic cores, in which Q IM This is the total amount of iron contained in nanoparticles, particularly magnetic cores. In some other cases, this percentage can be a ratio S. MFI / S M SM FI The size of the nanoparticles, especially the magnetosomes, is measured before the free iron is released from the nanoparticles, particularly in the magnetosomes.

[0356] The present invention also relates to a method for treating anemia or anemia syndrome, wherein the amount of free iron dissociated or released from nanoparticles, particularly magnetosomes, is greater than the amount of iron contained in an individual body part. In some cases, the amount of free iron dissociated or released from nanoparticles (particularly magnetosomes) is 1.00001, 1.1, 2, 5, 10, or 50 times greater than the amount of iron contained in an individual body part, preferably before treatment begins. In some other cases, the amount of free iron dissociated or released from nanoparticles, particularly magnetosomes, is greater than 10. -100 10 -50 10 -20 10 -10 10 -5 10 -2 10 -1 1, 10 or 10 3 The preferred content of free iron per nanoparticle, particularly magnetic particles, is gram of free iron or per gram of nanoparticle, particularly magnetic particles, or gram of free iron per cubic centimeter of body portion.

[0357] The present invention also relates to a method for treating anemia or anemia-related diseases, wherein the amount of free iron dissociated or released from nanoparticles, particularly magnetosomes, is less than 10. 100 10 50 10 20 10 10 10 5 10 3 ,10,1,10 -1 10 -5 10 -10 Or 10 -50The preferred content of free iron per nanoparticle, particularly magnetic particles, is gram of free iron or per gram of nanoparticle, particularly magnetic particles, or gram of free iron per cubic centimeter of body portion.

[0358] The present invention also relates to a method for treating anemia or anemia-related diseases, wherein the treatment is due to, involves, or is caused by:

[0359] i) Internalization of nanoparticles in cells,

[0360] ii) Nanoparticles are exocrinated from cells.

[0361] iii) Changes in structure, geometry, composition, size, size distribution, surface charge of nanoparticles, and / or

[0362] iv) Applications of radiation or sound waves in nanoparticles

[0363] In some cases, variations in the properties of nanoparticles, where the properties of nanoparticles can be structure, geometry, composition, size, size distribution, or surface charge of the nanoparticles, are greater than 10% of that property. -50 10 -10 The changes are 1, 5, 10, or 50 percent. In some other cases, the changes in the properties of the nanoparticles are less than 100%, 99%, 90%, 80%, 70%, 50%, 25%, 10%, or 5 percent. In some cases, this percentage can be equal to P. AT / P BT , where P AT / P BT These are the values ​​of this property before and after anemia treatment, respectively.

[0364] The present invention also relates to a method for treating anemia or anemia-related diseases, wherein the radiation is selected from the group consisting of X-rays, light waves, microwaves, radio waves, and sound waves. In some cases, the application of radiation to nanoparticles increases the amount of free iron dissociated or released from the nanoparticles, preferably greater than 1.0001, 1.1, 2, 5, 10, 10. 3 10 5 Or 10 10 A factor, where the factor can be equal to Q. FIR / Q FI Q FIR and Q FI These are the amounts of free iron released or dissociated from the nanoparticles before and after radiation is applied to them.

[0365] This invention also relates to a method for treating anemia or anemia disease, wherein the power of the radiation is between 10 -10 and 10 10Watts or watts per cubic centimeter or watts per cubic centimeter or watts per cell

[0366] The present invention also relates to a method for treating anemia or anemia disease, wherein radiation is sequentially applied to nanoparticles, the sequence comprising the following steps:

[0367] i) Apply radiation at time t1:

[0368] ii) During time t2: No radiation is applied or radiation with a lower power than that applied during time t1.

[0369] In some cases, sequentially applying radiation to nanoparticles or magnetosomes increases the amount of free iron dissociated or released from the nanoparticles or magnetosomes, preferably at amounts greater than 1.0001, 1.1, 2, 5, 10, 10. 3 10 5 Or 10 10 The factor increases, where the factor can be equal to Q. FISR / Q FIR， Q FISR and Q FIR These are the amounts of free iron released or dissociated from nanoparticles or magnetosomes after sequential and discontinuous irradiation, respectively.

[0370] In one embodiment of the invention, the treatment according to the invention is sonodynamic therapy.

[0371] In some cases, sonodynamic therapy can be defined as a therapy that triggers a therapeutic activity by: i) applying low-intensity sound waves to nanoparticles or body parts; or ii) using nanoparticles as sound sensitizers. In some cases, sonodynamic therapy is defined as a therapy where the temperature increase is less than 10°C. 50 10 5 10 3 500, 200, 100, 50, 25, 10, 5, 2 or 1 degree Celsius, and / or the percentage of compound dissociation is greater than 10 percent. -5 10 -2 10 -1 , 1, 10, 10 3 Or 10 7 .

[0372] In some cases, the percentage of dissociation of a compound or the percentage of dissociated compounds can be defined as the following ratios: i) the quantity or mass of compounds that are not linked or bound to the nanoparticles or have dissociated, preferably after the application of acoustic waves or radiation, and ii) the quantity or mass of compounds that are linked to the nanoparticles or do not dissociate, preferably before or without the application of acoustic waves or radiation.

[0373] In some other cases, sonodynamic therapy is defined as a therapy in which the temperature increase is greater than 10°C. 5 10 3 500, 200, 100, 50, 25, 10, 5, 2 or 1 degree Celsius, and / or the percentage of compound dissociation is less than 10 percent. -5 10 -2 10 -1 , 1, 10, 10 3 Or 10 7 .

[0374] The present invention also relates to nanoparticles used according to the invention, wherein the application of sound waves or radiation to the nanoparticles or body parts causes an increase in temperature of the body parts or nanoparticles, said temperature increase being between 10°C and 10°C. -10 and 10 10 10 -5 and 10 5 10 -1 and 10 4 Or between 1 and 30 degrees Celsius. In some cases, the temperature of the body parts or nanoparticles can be between 10 and 30 degrees Celsius. -10 and 10 10 10 -5 and 10 5 or between 10 -1 and 10 4 The temperature rises by degrees Celsius.

[0375] In some other cases, temperature can be measured at the nanoscale, i.e., values ​​smaller than 2, 5, 10, 10. 3 10 5 Or 10 9 Nanoparticles have a size smaller than the following: i) 1, 2, 5, 10, 10 3 10 5 Or 10 9 The size of the nanoparticles, or ii) 10 5 10 3 10 2 , 10 or 1 nanometer.

[0376] In some cases, temperature can be measured on a macroscopic scale, i.e., a scale that is at least 1.001, 1.1, 1.2, 1.5, 5, 10, 10 greater than the nanoscale. 3 Or 10 5 Factors, ii) are 1, 10, 10 larger than the size of nanoparticles. 3 10 5 Or 10 9 or iii) containing greater than 2, 5, 10, 103 10 5 Or 10 9 Nanoparticles

[0377] In one embodiment of the invention, the temperature of the body part or nanoparticle exposed to the sound waves increases, ΔT being the temperature increase above physiological temperature or above the body part temperature of the nanoparticles reached before the application of the sound waves or radiation. In some cases, ΔT = T NPBP – T BP T NPBP It is the temperature or temperature increase of body parts containing nanoparticles exposed to sound waves or radiation, T BP Yes: i) the temperature or temperature rise of body parts that do not contain nanoparticles exposed to sound waves or radiation, or ii) the temperature or temperature rise of body parts that do not contain nanoparticles not exposed to sound waves or radiation. In some other cases, ΔT may occur or be measured: i) in body parts containing nanoparticles, ii) in nanoparticle regions, iii) in body parts without nanoparticles, iv) in both body parts without nanoparticles and nanoparticle regions, or v) in nanoparticle regions and not in body parts without nanoparticles. Preferably, a greater temperature rise occurs in body parts containing nanoparticles or in nanoparticle regions compared to body parts without nanoparticles.

[0378] In some cases, the temperature increase ΔT can be the difference between the temperature measured or occurring when sound waves or radiation are applied sequentially to the nanoparticles and the temperature measured or occurring when sound waves or radiation are applied continuously to the nanoparticles.

[0379] The present invention also relates to nanoparticles used according to the invention, wherein the application of sound waves or radiation to the nanoparticles or body parts causes an increase in temperature of the body parts or nanoparticles greater than 0.01, 0.1, 1, 2, 5, 10, 30, 50, 100, or 1000 degrees Celsius. In some cases, when sound waves or radiation are applied to the nanoparticles or body parts, the temperature of the body parts or nanoparticles increases beyond 0.01, 0.1, 1, 2, 5, 10, 30, 50, 100, or 1000 degrees Celsius.

[0380] In one embodiment of the invention, the sound wave or radiation, preferably at a thermal frequency, causes a temperature increase, preferably greater than 0.1, 1, 2, 5, 10, or 10 °C. 2 Or 10 3 Temperature in degrees Celsius, preferably with a thermoacoustic frequency greater than 10. -20 10 -10 10 -5 10 -3 10-1 , 1, 10, 10 3 10 5 10 10 Or 10 20 hertz

[0381] The present invention also relates to nanoparticles for use according to the invention, wherein the application of sound waves or radiation to the nanoparticles or body parts causes an increase in temperature of the body parts or nanoparticles below 10°C. 100 10 50 10 20 10 10 10 5 10 3 10 2 50, 30, 10, 5, 2, 1, 0.1 or 0.01 degrees Celsius. In some cases, when sound waves or radiation are applied to nanoparticles or body parts, the temperature of the body part or nanoparticles rises by less than 10 degrees Celsius. 3 10 2 50, 30, 10, 5, 2, 1 or 0.1 degrees Celsius.

[0382] In one embodiment of the invention, the frequency of the sound wave or radiation is non-thermal. In this case, the frequency of the sound wave or radiation is such that it does not cause a temperature increase, or its induced temperature increase is less than 10°C. 3 10 2 The temperature is 10, 5, 2, 1, or 0.1 degrees Celsius. In this case, the frequency of the sound wave or radiation is preferably below 10. 20 10 10 10 5 10 3 10 1 , 1, 10, 10 -3 10 -5 10 -10 Or 10 -20 hertz.

[0383] In one embodiment of the invention, a suitable temperature rise range ΔT is between 3 degrees Celsius and 28 degrees Celsius. The minimum of this range (3 degrees Celsius) is estimated by exposing 100 microliters of water mixed with 100 micrograms of magnetic particles to a sound wave at 1.5 watts per square centimeter. In some cases, this minimum is achieved by reducing the intensity, power, or frequency of the sound wave by more than 1.5, 2, 5, 10, 50, or 10. 2 10 5 10 7 10 9 Or 10 20Factors, or by reducing the concentration of nanoparticles in body parts to greater than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 The factor can be reduced to greater than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 Or 10 20 The factor. The maximum value of this range (28 degrees Celsius) is estimated by exposing 45 micrograms of magnetic particles per cubic centimeter of tissue to 1.5 watts per square centimeter of sound waves. In some cases, this maximum value is achieved by increasing the intensity, power, or frequency of the sound waves by more than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 Factors, or by increasing the concentration of nanoparticles in body parts to greater than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 The factor can be increased by more than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 Or 10 20 The factors,

[0384] In another embodiment of the invention, T NPBP The suitable range is between 18 and 56 degrees Celsius. The minimum of this range (18 degrees Celsius) is estimated by exposing a suspension containing 100 microliters of water mixed with 100 micrograms of magnetic particles to a sound wave of 0.5 watts per square centimeter. In some cases, this minimum is determined by reducing the intensity, power, or frequency of the sound wave by more than 1.5, 2, 5, 10, 50, or 10. 2 10 5 10 7 10 9 Or 10 20 Factors, or by reducing the concentration of nanoparticles in body parts to greater than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 1020 The factor can be reduced to greater than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 Or 10 20 The factor. The maximum value of this range (56 degrees Celsius) is estimated by exposing 45 micrograms of magnetic particles per cubic centimeter of tissue to 1.5 watts per square centimeter of sound waves. In some cases, this maximum value is achieved by increasing the intensity, power, or frequency of the sound waves by more than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 Factors, or by increasing the concentration of nanoparticles in body parts to greater than 1.5, 2, 5, 10, 50, 10 2 10 5 10 7 10 9 Or 10 20 The factor can be increased by more than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 Or 10 20 The factors,

[0385] In another embodiment of the invention, T BP The appropriate range is between 13 degrees Celsius and 32 degrees Celsius. The minimum value of this range (13 degrees Celsius) is estimated by exposing the aqueous solution to a sound wave at 0.5 watts per square centimeter. In some cases, this minimum is achieved by reducing the intensity, power, or frequency of the sound wave by more than 1.5, 2, 5, 10, 50, or 10. 2 10 5 10 7 10 9 Or 10 20 The factor can be reduced to greater than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 10 9 Or 10 20 The factor. The maximum value of this range (32 degrees Celsius) is estimated by exposing tissue to sound waves of 1 watt per square centimeter. In some cases, this maximum value is achieved by increasing the intensity, power, or frequency of the sound waves by more than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 710 9 Or 10 20 The factor can be increased by more than 1.5, 2, 5, 10, 50, 10. 2 10 5 10 7 Or 10 9 The factors,

[0386] In one embodiment of the invention, the application of sound waves or radiation to the nanoparticles results in a saturation temperature (ST), or sound waves or radiation are applied to the nanoparticles until the saturation temperature is reached. In some cases, the saturation temperature may be a desired temperature.

[0387] In one embodiment of the invention, the application of sound waves or radiation ceases once the saturation temperature is reached, preferably to avoid overheating. Preferably, the saturation temperature is the maximum temperature achievable during the application of sound waves or radiation, or, in other words, is specified as t during the application of sound waves or radiation. s Either t1 or t3, with a variation not exceeding 1%, 5%, 10%, 50%, 75%, or 10 percent. 2 Or 10 3 The temperature.

[0388] Time t s t1, t3, preferably, at time t i After that, at time t i It is the initial time at which sound waves or radiation are applied. In some cases, t s Less than t i In some other cases, t i / (t i +t s (greater than 10) -9 10 -7 10 -5 10 -4 10 -3 10 -2 10 -1 0.5, 0.75, or 0.9, and in some other cases, t s / t i Greater than 10 -9 10 -6 10 -3 10 -1 , 1, 10, 10 3 10 6 Or 10 9 In some other cases, t s / t i Less than 10 9 10 6 10 3,10,1,10 -1 10 -3 10 -6 Or 10 -9 .

[0389] In another embodiment of the invention, t1 = t i +t s ,

[0390] In some cases, ST can be: i) greater than -270, -200, -100, -50, 0, 1, 10, 10 3 Or 10 5 (i) The temperature in the presence of nanoparticles was significantly higher than that in the absence of nanoparticles, by at least 1.00001, 1.1, 1.2, 1.5, 2, 5, 10, 10 degrees Celsius. 3 10 5 Or 10 9 factor.

[0391] In some other cases, ST can be: i) less than 10 20 10 5 10 3 , 10, 1, -100 or -200 °C, degrees Celsius, or ii) compared with the case with nanoparticles, its significance decreased by at least 1.00001, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 10 5 Or 10 9 factor.

[0392] In some other cases, ST can be between -270 and 10. 50 -100 and 10 20 0 and 10 10 10 and 10 5 37 and 10 3 or between 41 and 10 3 °C.

[0393] In one embodiment of the invention, a suitable range for the value of ST is between (37±4) degrees Celsius and (73±4) degrees Celsius. In some cases, the minimum value of this range, (37±4) degrees Celsius, can be reduced, for example, by greater than 5, 10, 20, 50, or 100 degrees Celsius, by using a device or substance (such as ice) that lowers the temperature of the body part or by reducing the intensity, power, or frequency of sound waves or by reducing the concentration of nanoparticles. In some other cases, the maximum value of this range, (73±4) degrees Celsius, can be increased, for example, by greater than 1, 5, 10, 20, 50, or 100 degrees Celsius, by using a device or substance that increases the temperature of the body part or by increasing the intensity, power, or frequency of sound waves or by increasing the concentration of nanoparticles.

[0394] In one embodiment of the invention, a compound is preferably applied to a body part, bound to or attached to nanoparticles, preferably before or without the application of sound waves or radiation to the nanoparticles.

[0395] In one embodiment of the invention, the compound is attached to the nanoparticles or does not dissociate from the nanoparticles when: i) the distance from the nanoparticles is less than 10... 5 10 3 ii) The compound is bonded to or connected to the nanoparticles, preferably by hydrogen bonds, van der Waals forces, London forces, covalent bonds, metallic bonds, or ionic bonds; iii) The compound cannot be magnetically separated from the nanoparticles; iv) The compound is associated with or connected to the nanoparticles or is located at a distance of less than 10, 1, or 10 nanometers from the nanoparticles. -1 10 -3 10 -6 Or 10 -9 The percentage of the compound in centimeters, greater than 99, 90, 75, 50, 30, 20, 10, 5, 2 or 1 percent, wherein the percentage may be or represents the ratio of the quantity or mass of the compound connected or associated with the nanoparticles before magnetic separation to the quantity or mass of the compound connected or associated with the nanoparticles after magnetic separation.

[0396] The present invention also relates to nanoparticles used according to the invention, wherein a compound is attached to the nanoparticles and the application of acoustic waves to the nanoparticles causes the compound to dissociate from the nanoparticles.

[0397] In some cases, the compound may not bind to or be attached to the nanoparticles, or may dissociate from the nanoparticles if: i) it is at a distance greater than 10 from the nanoparticles, the nanoparticle surface, or the nanoparticle coating. -3 10 -1 1, 5, 10, 100, 10 3 or 10 5ii) It is not bonded or connected to nanoparticles by hydrogen bonds, van der Waals forces, London bonds, covalent bonds, metallic bonds, or ionic bonds; iii) It can be separated from nanoparticles by the magnetic properties of the compound, preferably using a magnet that can attract nanoparticles; iv) It is associated or connected to nanoparticles or the distance between it and nanoparticles is less than 10, 1, 10. -1 10 -3 10 -6 or 10 -9 The percentage of the compound in centimeters is less than 99, 90, 75, 50, 30, 20, 10, 5, 2 or 1 percent.

[0398] In some cases, magnetic separation may include separating the compound from the nanoparticles by applying a magnetic field to the nanoparticles, the strength of which varies spatially, preferably using a magnetic field with a strength below 10, 1, 10. -1 10 -3 or 10 -9 A magnet of Tesla strength, wherein the strength is preferably measured on or near the surface of the magnet and decreases with increasing distance from the magnet.

[0399] In some other cases, the compound may be attached to or bound to the nanoparticles or may not dissociate from them. In this case, its location may be less than 10 units away from the nanoparticles or the surface or coating of the nanoparticles. 100 10 50 10 10 10 5 10 2 10, 5, 2 or 1 nanometer or between 10 -3 And 1 nanometer.

[0400] In one embodiment of the invention, the sound waves or radiation are preferably associated with, or combined with, or induced, generated, caused or caused by the movement, vibration or oscillation of the compound, preferably after the compound is dissociated from the nanoparticles.

[0401] In one embodiment of the invention, the compound is a therapeutic, immunogenic, metabolic, luminescent, fluorescent, radioactive, diagnostic, biological, or chemical compound. In some cases, the compound may be or represent a value greater than 1, 10, or 10. 2 10 3 10 5 10 7 10 10 10 20 Or 10 50Components of the compound. The compound is preferably linked to or bound to the nanoparticles. In some cases, the compound can dissociate from the nanoparticles under the application of acoustic waves or radiation. In some cases, more than 10% -5 10 -3 10 -1 Compounds of 1, 5, 10, 25, 50, 75, 85, or 90% dissociate from the nanoparticles, where this percentage can be expressed as the ratio between the amount of compound dissociating from the nanoparticles after or below the application of acoustic waves or radiation and the amount of compound attached to or bound to the nanoparticles before or without the application of acoustic waves or radiation. In some cases, the number of compounds attached to or bound to a single nanoparticle is greater than 1, 2, 5, 10, or 90%. 3 10 5 Or 10 10 In some other cases, the number of compounds linked to or bound to a single nanoparticle is less than 2, 5, 10, or 10⁻⁶. 3 10 5 Or 10 10 In other cases, the percentage of dissociated compounds can increase by at least 1.01, 1.1, 2, 5, 7, 10, 10% between the application of sound waves or radiation to the nanoparticles. 2 Or 10 5 Factors.

[0402] In one embodiment of the invention, the compound is part of the nanoparticles. In this case, it can be free iron or free oxygen, preferably in ionic form, preferably dissociated from, leaked from or diffused from the nanoparticles, preferably after or under the application of sound waves or radiation to the nanoparticles or body part, preferably after the nanoparticles have dissolved or degraded, and preferably after the nanoparticles have been applied to or into the body part.

[0403] In another embodiment of the invention, the ratio between the mass, quantity, or weight of the compound is preferably correlated with the individual nanoparticles, wherein the mass, quantity, or weight of the individual nanoparticles is less than 10. 20 10 9 10 5 10 2 ,2,1,10 -2 10 -5 10 -9 Or 10 -20 .

[0404] In another embodiment of the invention, the ratio between the mass, quantity, or weight of the compound is preferably associated with a single nanoparticle, wherein the mass, quantity, or weight of the single nanoparticle is greater than 10. 20 10 910 5 10 2 ,2,1,10 -2 10 -5 10 -9 Or 10 -20 .

[0405] In one embodiment of the invention, a suitable numerical range for the number of compounds preferably attached to a single nanoparticle is 1 to 178, wherein the minimum value of 1 corresponds to the minimum number of compounds that can be attached to a single nanoparticle, and the maximum value of 178 corresponds to the number of RhB molecules attached to a single magnetosome in patent WO 2017 / 068252, which is incorporated herein by reference and can at least partially dissociate from a single magnetosome. In some cases, the maximum value of 178 can be increased, preferably by 5, 10, or 10 times. 3 10 7 10 10 Or 10 20 (i) Reduce the size or mass of the compound attached to the nanoparticles, preferably greater than 1.1, 2, 5, 10, 10 3 10 7 10 10 , or 10 20 (ii) changing the type of link between the compound and the nanoparticle, or (iii) changing the method used to attach or bind the compound to the nanoparticle.

[0406] In a key embodiment of the invention, the sequential application of sound waves or radiation is used to achieve or enable a temperature or maximum temperature, preferably below the maximum temperature achievable by continuous application of sound waves or radiation during at least one sequence. On the one hand, heating at a lower temperature can lead to reduced toxicity compared to continuous application of sound waves or radiation. On the other hand, by generating a temperature gradient or a velocity or motion gradient of nanoparticles in at least one sequence, higher efficacy, preferably antitumor or anticancer efficacy, can be achieved, thereby triggering at least one therapeutic mechanism disclosed in the invention more effectively compared to continuous application of sound waves or radiation.

[0407] The present invention also relates to nanoparticles used according to the invention, wherein sequential application of sound waves or radiation to a body part or nanoparticles causes:

[0408] i) A series of temperature increases in the body part or nanoparticles, followed by a temperature decrease in the body part or nanoparticles, and / or

[0409] ii) A series of dissociations of the compound from the nanoparticles, followed by non-dissociations of the compound with the nanoparticles.

[0410] In one embodiment of the invention, sound waves or radiation are applied sequentially, preferably to body parts or nanoparticles, when: i) it is not applied continuously over time, ii) it is not applied at a continuous power, intensity or frequency that varies over time, or iii) it creates, associates or generates at least one sequence.

[0411] In some cases, time t1 is the duration of the applied sound wave or radiation.

[0412] In some other cases, time t2 is the duration during which no sound waves or radiation are applied.

[0413] In some other cases, time t3 is the duration of the application of sound waves or radiation, whose intensity, energy, power, or frequency is lower than that applied to the nanoparticles during time t1 or t2.

[0414] In some cases, the sequence may correspond to or may be applying sound waves or radiation during time t1 and then not applying sound waves or radiation during time t2.

[0415] In some other cases, the sequence may correspond to or be applied during time t1, followed by the application of another sound wave or radiation during time t3, wherein the intensity, energy, or frequency of the sound wave or radiation applied during time t3 is lower than the power, energy, or frequency of the sound wave or radiation applied during time t1.

[0416] In one embodiment of the invention, time t i This refers to the duration of the heating step.

[0417] In one embodiment of the invention, the heating step is a step in which the temperature of the body part or nanoparticles is increased.

[0418] In one embodiment of the invention, the temperature rise of the heating step has at least one of the following properties: i) it is greater in the presence of nanoparticles than in the absence of nanoparticles; ii) it is greater during t1 than during t2 or t3; iii) it is greater than or equal to 10. -20 10 -5 10 -3 10 -1 1, 2, 5, 10, 25, 50, 100, 200, 500, 10 3 10 5 Or 10 9 Celsius, iv) which causes an increase in initial temperature or is characterized by an increase in initial temperature, is also specified as the initial slope of temperature increasing over time, ΔT / δt, which is greater than 10. -40 10 -20 10-10 10 -7 10 -5 10 -3 10 -1 1, 2, 5, 10, 10 2 10 3 Or 10 5 The temperature measured in degrees Celsius per second or per gram of nanoparticles or body parts, or in degrees Celsius per second or per cubic centimeter of nanoparticles or body parts, (v), ensures that the maximum temperature reached during the heating step remains below 25, 30, 37, 39, 41, 45, 50, 100, 10 3 10 5 10 9 Or 10 11 Celsius, or vi)

[0419] It raises the temperature by at least 10 degrees compared to the temperature achieved by applying sound waves or radiation without nanoparticles. -5 10 -3 10 -1 1, 2, 5, or 10, 10 3 10 5 , or 10 9 Celsius.

[0420] In one embodiment of the invention, the temperature rise in the heating step has at least one of the following properties: i) it is below or less than 10°C. 50 10 9 10 5 10 3 , 10, 5, 2, 1, 10 -1 10 -3 Or 10 -5 (ii) that causes or is characterized by ΔT / δt, which is below 10 degrees Celsius. 50 10 20 10 10 10 3 10 2 , 10, 5, 2, 1, 10 -1 10 -3 10 -5 10 -7 10 -10 10 -20 Or 10 -40 (iii) The highest temperature reached during the heating step is maintained below 10 degrees Celsius per second or per gram of nanoparticles or body part. 11 10 9 105 10 3 100, 50, 45, 41, 39, 37, 30, 25, 10, 5, 0, -100, -200 or -273 degrees Celsius, iv) It is 10 degrees lower than the temperature rise achieved by applying sound waves or radiation without nanoparticles. -50 10 -5 10 -3 10 -1 1, 2, 5, or 10, 10 3 10 5 , or 10 9 (or v) which results in or is characterized by a ΔT / δtu value less than 10 100 10 40 10 20 10 5 10 3 10 2 , 10, 5, 2, 1, 10 -1 10 -3 10 -5 10 -7 10 -20 Or 10 -40 The temperature per second is measured in degrees Celsius per gram or per gram of nanoparticles or body parts.

[0421] In one embodiment of the invention, the temperature rise, or the initial slope of the rise, preferably a heating step, is measured or occurs under the following conditions: i) physiological temperature, ii) the temperature of an individual or body part before or after the heating step, or without the heating step, iii) the temperature of an individual or body part during a cooling step, or iv) a temperature rise achieved by applying sound waves or radiation to the body part without nanoparticles.

[0422] In one embodiment of the invention, the temperature increase that preferably occurs or is measured during the heating step is the temperature difference between the measured temperatures: i) before and after the application of the sound wave or radiation, ii) at the beginning and end of t1.

[0423] In some cases, the temperature increase that preferably occurs or is measured during the heating step can be greater than 10°C. -20 10 -3 10 -2 10 -1 , 1, 10, 10 2 10 3 Or 10 5 Celsius.

[0424] In some other cases, the temperature increase that preferably occurs or is measured during the heating step may be less than 10°C. 20 10 5 10 3 10 2 ,10,1,10 -1 10 -2 Or 10 -3 Celsius.

[0425] In other cases, the temperature increase that preferably occurs or is measured during the heating step can be 10 -50 and 10 50 10 -5 and 10 50 10 -1 and 10 10 10 -5 and 10 3 or between 10 -2 and 10 3 Between degrees Celsius.

[0426] In other cases, the temperature increase that preferably occurs or is measured during the heating step is greater than 10°C in the presence of nanoparticles than in the absence of nanoparticles. -50 10 -20 10 -5 10 -3 10 -2 10 -1 , 1, 10, 10 2 10 3 Or 10 5 Celsius.

[0427] In one embodiment of the invention, as derived from Table 2, a suitable range of temperature increase is between 0 °C and 36 °C, the maximum value of which (36 °C) can be increased, for example, by more than 1, 5, 10, 20, 50 or 100 degrees Celsius, preferably when the temperature of the body part increases, for example by using an instrument or a substance that can increase the temperature of the body part or by increasing the intensity, power or frequency of sound waves to increase the concentration of nanoparticles.

[0428] In one embodiment of the invention, for the continuous application of sound waves or radiation, t2 and / or t3 = 0 seconds.

[0429] In some cases, t1, t2, and / or t3 are chosen, or are such that the temperature reached after n sequences of total duration n.(t1+t2) or n.(t1+t3) is lower than the temperature reached at the end of a continuous application of sound waves or radiation for a duration of n.t1 by a factor of at least 1.00001, 1.1, 2, or 5, where the heating time is the same for both the sequences and the continuous application of sound waves or radiation. n can be between 1 and 10. 100 Integers between

[0430] The present invention also relates to nanoparticles used according to the invention, wherein the application of sound waves or radiation to the nanoparticles or body parts preferably induces a temperature increase in at least one heating step, wherein:

[0431] i) Greater than 10 in pathological sites -10 10 -5 10 -3 10 -1 1, 5 or 10 degrees Celsius, and / or

[0432] ii) In healthy areas, preferably surrounding pathological areas, less than 10 10 10 5 10 3 100, 50, 20, 10, 5, 2, 1, 10 -1 10 -5 Or 10 -10 Celsius

[0433] In another embodiment of the invention, time t2 or t3 is the duration of the cooling step.

[0434] In one embodiment of the invention, the cooling step is a step in which the temperature of the body part decreases. In some cases, the temperature decrease in the cooling step can be the magnitude or absolute value of this reduction.

[0435] In one embodiment of the invention, the temperature reduction of the cooling step has at least one of the following properties: i) it is greater in the presence of nanoparticles than in the absence of nanoparticles; ii) it is greater during t2 or t3 than during t1; iii) it is greater than 10. -20 10 -5 10 -3 10 -1 1, 2, 5, 10, 25, 50, 100, 200, 500, 10 3 10 5 or10 9Celsius, iv) which causes or is characterized by an initial temperature decrease, which is also specified as the initial slope of the temperature decrease over time, ΔT / δt, which is greater than 10. -40 10 -20 10 -10 10 -7 10 -5 10 -3 10 -1 1, 2, 5, 10, 10 2 10 3 Or 10 5 The temperature is measured in degrees Celsius per second or per gram of nanoparticles or body parts, or in degrees Celsius per cubic centimeter of nanoparticles or body parts, v) such that the minimum temperature reached during the cooling step is maintained at -273, -150, -100, -75, -50, -30, -10, 0, 5, 10, 25, 30, 37, 39, 41, 45, 50, 100, 10 3 10 5 10 9 Or 10 11 (vi) It reduces the temperature by at least 10 degrees Celsius compared to the temperature achieved without the application of sound waves or radiation in the absence of nanoparticles. -5 10 -3 10 -1 1, 2, 5, 10, 10 3 10 5 Or 10 9 Celsius, or v), which results in or is characterized by a ΔT / δt value greater than 10. -40 10 -20 10 -10 10 -7 10 -5 10 -3 10 -1 1, 2, 5, 10, 10 2 10 3 Or 10 5 The temperature per second is measured in degrees Celsius per gram of nanoparticles or per body part.

[0436] In another embodiment of the invention, the temperature of the cooling step has at least one of the following properties: i) it is lower in the presence of nanoparticles than in the absence of nanoparticles, ii) it is below 10°C. 50 10 9 10 5 10 3 , 10, 5, 2, 1, 10 -110 -3 Or 10 -5 (iii) Celsius, which results in or is characterized by a ΔT / δt value below 10. 50 10 20 10 10 10 3 10 2 , 10, 5, 2, 1, 10 -1 10 -3 10 -5 10 -7 10 -10 10 -20 Or 10 -40 The temperature is measured in degrees Celsius per second, or per gram of nanoparticles, or per cubic centimeter of body part. (iv) The minimum temperature reached during the cooling step is maintained below 10°C. 11 10 9 10 5 10 3 100, 50, 45, 41, 39, 37, 30, 25, 10, 5, 0, -100, -200 or -273 degrees Celsius (v) It reduces the temperature by at least 10 degrees Celsius compared to the absence of nanoparticles. -50 10 -5 10 -3 10 -1 1, 2, 5, or 10, 10 3 10 5 , or 10 9 Celsius, or vi) This results in or is characterized by a ΔT / δt value below 10. 100 10 40 10 20 10 5 10 3 10 2 , 10, 5, 2, 1, 10 -1 10 -3 10 -5 10 -7 10 -20 Or 10 -40 The temperature per second is measured in degrees Celsius per gram of nanoparticles or per body part.

[0437] In one embodiment of the invention, the temperature decreases, and the initial slope of the temperature decrease, preferably during the cooling step, is measured or occurs as follows: i) the temperature of the individual or body part in the absence of the cooling step, or before or after the cooling step, or ii) the temperature of the individual or body part during the heating step.

[0438] In one embodiment of the invention, the temperature reduction that preferably occurs or is measured during the cooling step is the temperature difference between the temperatures measured between the beginning and end of t2 or t3.

[0439] In some cases, the temperature reduction that preferably occurs or is measured during the cooling step can be greater than 10°C. -20 10 -3 10 -2 10 -1 , 1, 10, 10 2 10 3 Or 10 5 Celsius.

[0440] In some other cases, the temperature reduction that preferably occurs or is measured during the cooling step can be less than 10°C. 20 10 5 10 3 10 2 ,10,1,10 -1 10 -2 Or 10 -3 Celsius.

[0441] In other cases, the temperature reduction that preferably occurs or is measured during the cooling step can be between 10°C and 10°C. -50 and 10 50 10 -5 and 10 50 10 -1 and 10 10 10 -5 and 10 3 or between 10 -2 and 10 3 Degrees Celsius.

[0442] In some other cases, the temperature reduction that preferably occurs or is measured during the cooling step can be: i) in some cases, greater than 10°C in the presence of nanoparticles than in the absence of nanoparticles. -50 10 -20 10 -5 10 -3 10 -2 10 -1 , 1, 10, 10 2 10 3 or 105 (ii) In some other cases, the temperature is smaller in the presence of nanoparticles than in the absence of nanoparticles, exceeding 10 degrees Celsius. -50 10 -20 10 -5 10 -3 10 -2 10 -1 , 1, 10, 10 2 10 3 Or 10 5 Celsius.

[0443] In one embodiment of the invention, time t1 is the duration of the dissociation step, wherein the dissociation step is the step of the compound dissociating nanoparticles.

[0444] In some cases, greater than 0.01, 0.1, 1, 5, 10, 25, 50, 75, 80, or 90 percent of the compound is dissociated or dissociated from the nanoparticles, preferably during the dissociation step.

[0445] In some other cases, less than 100%, 99%, 90%, 80%, 75%, 50%, 20%, 10%, 5%, 2%, 1%, or 0.1% of the compound is dissociated or separated from the nanoparticles, preferably during the dissociation step.

[0446] In some other cases, between 10% -1 The compounds are dissociated or detached from the nanoparticles at a rate between 100%, 1 and 99%, 1 and 50%, or between 2% and 10%, preferably during the dissociation step.

[0447] This percentage can be equal to the ratio between the number, concentration, or mass of compounds that have dissociated from the nanoparticles and the total number or concentration of compounds that have not dissociated from and / or attached to the nanoparticles.

[0448] In another embodiment of the invention, time t2 or t3 is the duration of the non-dissociation step, wherein the non-dissociation step is the step in which the compound does not dissociate from the nanoparticles.

[0449] In some cases, when the percentage of the compound in the dissociated nanoparticles is low, the compound will not dissociate from the nanoparticles, preferably more than 1.00001, 1.1, 1.2, 1.5, 2, 5, 10, 10 lower than that achieved or obtained during the dissociation step. 5 Or 10 10 The factors,

[0450] In some cases, the value of t2 can be the same as the value of t1.

[0451] In one embodiment of the invention, times t1, t2, or t3 are 10 -3 10 -2 10 -1 , 1, 10, 10 2 or10 3 10 5 10 20 10 100 Or 10 1000 Minutes are shorter. In some cases, t1, t2, or t3 are less than 10. -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 Or 10 9 The second is even shorter.

[0452] In another embodiment of the invention, the time t1, t2, or 3 is greater than 10. -3 10 -2 10 -1 , 1, 10, 10 2 , or 10 3 Minutes are longer. In some cases, t1, t2, or t3 are longer than 10. -100 10 -50 10 -20 10 -9 10 -7 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 5 10 7 or 10 9 Seconds are longer.

[0453] In one embodiment of the invention, the time t1, t2, or t3 is shorter than the pulse time, preferably by at least 1.1, 1.5, 2, 5, 10, or 10. 2 10 3 10 5 10 7 10 9 10 12 10 15 Or 10 20 Factors.

[0454] In another embodiment of the invention, the time t1, t2, or t3 is longer than the pulse time, preferably by at least 1.1, 1.5, 2, 5, 10, or 10. 2 10 3 10 5 10 7 10 9 10 12 10 15 Or 10 20 Factors.

[0455] In yet another embodiment of the invention, a pulse is defined as a pulse shorter than 10. 6 10 3 ,1,10 -3 10 -6 Or 10 -9 Within a time period of seconds, sound waves or radiation, preferably sound wave or radiation power, energy or intensity, are applied to nanoparticles or body parts.

[0456] In one embodiment of the invention, the ratio of t1 / t2 or t2 / t3 is less than 10. -9 10 -6 10 -3 10 -1 , 1, 10, 10 3 10 6 10 9 10 20 10 50 Or 10 100 .

[0457] In another embodiment of the invention, the ratio of t1 / t2 or t2 / t3 is greater than 10. -100 10 -50 10 -20 10 -9 10 -6 10 -3 10 -1 , 1, 10, 10 3 10 6 Or 10 9 .

[0458] In one embodiment of the invention, the intensity, energy, power, or frequency of the sound wave or radiation applied during t3 is at least 1.1, 1.3, 1.5, 2, 5, 10, or 10 lower than the intensity, energy, power, or frequency of the sound wave or radiation applied during t1. 2 10 3 10 5 10 7 Or 10 9 .

[0459] In one embodiment of the invention, suitable values ​​range from 0.2 to 0.43 minutes, for t1, and from 0.2 to 0.36 minutes, for t2. The minimum and maximum values ​​of these ranges are estimated by sequentially exposing 500 micrograms of magnetosomes mixed in 100 microliters of water to sound waves at a frequency of 3 MHz and a power of 1.5 watts per square centimeter, as described in embodiment 1(c), and by estimating the minimum and maximum values ​​of t1 and t2 between two different sequences.

[0460] In another embodiment of the invention, the minimum value of the range of t1 and t2 values ​​can be reduced, for example, to a value greater than 1.5, 2, 5, 10, 10. 3 10 6 Or 10 9 This factor can be increased by increasing the number of nanoparticles in body parts, for example, by increasing by 1.5, 2, 5, 10, 10 3 10 6 Or 10 9 The factor is achieved by reducing the diffusion of nanoparticles from body parts or the degradation of nanoparticles between different sequences. This can also be achieved by increasing the power, intensity, or frequency of the sound waves, for example, by using values ​​greater than 1.5, 2, 5, 10, 10. 3 10 6 Or 10 9 The factor of . This can also be achieved by reducing the absorption of body parts that do not contain nanoparticles, and preferably by reducing the temperature change caused by such absorption. For t1 and t2, this can be achieved by using a device, substance, preferably different from a compound or nanoparticles, that heats the body part (seeking to affect t1) or cools the body part (seeking to affect t2).

[0461] In another embodiment of the invention, the maximum value of the range of t1 and t2 values ​​can be increased, for example, by values ​​greater than 1.5, 2, 5, 10, 10. 3 10 6 Or 10 9 Factors that can be mitigated by reducing the number of nanoparticles in body parts, for example, exceeding 1.5, 2, 5, 10, 10 3 10 6 Or 10 9 The factor can be achieved by increasing the diffusion of nanoparticles from body parts between different sequences or by increasing the degradation of nanoparticles. This can also be achieved by reducing the power, intensity, or frequency of sound waves, for example, by exceeding 1.5, 2, 5, 10, 10... 3 10 6 Or 10 9The factor of . This can also be achieved by increasing the absorption of body parts that do not contain nanoparticles, and preferably by increasing the temperature change caused by such absorption. For t1 and t2, this can be achieved by using a device, substance, preferably different from a compound or nanoparticles, that heats the body part (seeking to affect t1) or cools the body part (seeking to affect t2).

[0462] In some cases, heating, cooling, dissociation, or non-dissociation steps, preferably for durations t1, t2, or t3, in a sequence, preferably for durations t1+t2 or t1+t3, can be repeated more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 250, 500, 10 2 10 3 10 5 10 7 Or 10 9 Second-rate.

[0463] In some cases, the treatment may include more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 250, 500, 10 2 10 3 10 5 10 7 Or 10 9 sequence.

[0464] In some other cases, the treatment may include less than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 250, 500, 10 2 10 3 10 5 10 7 Or 10 9 sequence.

[0465] In one embodiment of the invention, the variation of times t1, t2, or t3 between the two sequences does not exceed 99.9%, 99%, 90%, 75%, 50%, 25%, 10%, or 10%. -1 %. In some cases, this percentage change can be estimated as the absolute value of (t1-t1') / t1, (t2-t2') / t2, or (t3-t3') / t3, where t1 and t1', t2 and t2', or t3 and t3' are the durations of two distinct heating / dissociation steps or cooling / non-dissociation steps belonging to two different sequences.

[0466] In one embodiment of the invention, the appropriate percentage range for (t1-t1') / t1 is between 5% and 43%, and the appropriate percentage range for (t2-t2') / t2 is between 5% and 44%. The minimum and maximum values ​​of these ranges are estimated by sequentially exposing 500 micrograms of magnetosomes mixed in 100 microliters of water to sound waves at a frequency of 3 MHz and a power of 1.5 watts per square centimeter, as described in embodiment 1(c), and by estimating the minimum and maximum values ​​of t1 and t2 between two different sequences.

[0467] In one embodiment of the invention, the duration (t1 + t2) or (t1 + t3) between two different sequences does not change by more than 99.9%, 99%, 90%, 75%, 50%, 25%, 10%, or 10 percent. -1 In some cases, this percentage change can be estimated as... ,or The absolute values ​​of , where (t1+t2) and (t1+t2)', or (t1+t3) and (t1+t3)', are the durations of two different sequences.

[0468] In one embodiment of the present invention, The appropriate range for the percentage is between 2% and 35%. The minimum and maximum values ​​of these ranges are estimated by sequentially exposing 500 micrograms of magnetosomes mixed in 100 microliters of water to sound waves at a frequency of 3 MHz and a power of 1.5 watts per square centimeter, as described in embodiment 1(c), and by estimating the minimum and maximum changes in the (t1+t2) values ​​between two different sequences.

[0469] In another embodiment of the invention, the minimum value of this range can be determined by ((t1-t1') / t1, (t2-t2') / t2, The value is given and can be reduced, for example, to more than 1.5, 2, 5, 10, 10. 3 10 6 Or 10 9 Factors. This can be achieved by increasing the number of magnetosomes in body parts, for example, exceeding 1.5, 2, 5, 10, 10. 3 10 6 Or 10 9 The factor is reduced by decreasing the diffusion of nanoparticles from body parts between different sequences or the degradation of nanoparticles. This can also be achieved by increasing the power, intensity, or frequency of the sound waves, for example, increasing by 1.5, 2, 5, 10, 10 3 10 6 Or 10 9Factors. This can also be achieved by reducing absorption in body parts that do not contain nanoparticles, and preferably by reducing the temperature rise caused by such absorption.

[0470] In another embodiment of the invention, the maximum value of this range can be determined by (t1-t1') / t1, (t2-t2') / t2, The value is given and can be increased, for example, up to 50%, 70%, 80%, 90%, 95%, 99%, or 99.9%. This can be achieved by reducing the number of magnetosomes, for example, by increasing it to more than 1.5, 2, 5, 10, or 10. 3 10 6 Or 10 9 Factors that can be influenced by increasing the diffusion of nanoparticles from body parts or the degradation of nanoparticles between different sequences. This can also be achieved by reducing the power, intensity, or frequency of sound waves, for example, by exceeding 1.5, 2, 5, 10, 10 3 10 6 Or 10 9 Factors. This can also be achieved by increasing absorption in body parts that do not contain nanoparticles, and preferably by increasing the temperature rise caused by this absorption.

[0471] In one embodiment of the invention, the treatment may include more than 1, 2, 5, 10, or 10 3 A treatment course includes: i) multiple or more than 1, 5, 10, or 100 treatment courses, ii) a series of heating or dissociation steps following a cooling or non-dissociation step.

[0472] In some cases, treatment courses can last for more than 1, 5, 10, 20, 50, or 10 weeks. 2 10 3 Or 10 5 minute

[0473] In some other cases, the treatment course can last less than 10 minutes. 50 10 20 10 10 10 5 10 3 10, 5, 2 or 1 minute

[0474] In some other cases, each course of treatment can be administered in multiples of 1, 5, 10, or 10. 2 10 3 10 5 10 10 Or 10 50 Minutes passed in intervals.

[0475] In some other cases, each treatment course can be administered with less than 10 50 1010 10 5 10 3 10 3 10 2 The time interval is 10, 5 or 1 minute.

[0476] The time elapsed between the two treatment courses is preferably longer than time t1, t2, t3, t1+t2, or t1+t3, and preferably greater than or less than 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 20, 50, 100, or 10. 3 10 5 Or 10 9 Factors

[0477] The present invention also relates to acoustic therapy or radiotherapy using sound waves or radiation, preferably sequential, more preferably sequential in space, on nanoparticles or body parts, wherein:

[0478] Applying sound waves or radiation to volume V1,

[0479] Nanoparticles, or body parts, are contained within volume V2.

[0480] Where V2 is less than V1, in some cases, the volume V2 can be smaller than V1 by an α factor, which can be greater than 1.0001, 1.1, 1.2, 2, 5, 10, 10. 3 10 5 Or 10 20或 By a factor or volume greater than 10 -5 10 -1 1, 5, 10, 10 3 Or 10 5 Cubic nanometers or cubic centimeters. In some other cases, the volume V2 can be smaller than V1 by an α factor that can be less than 10. 20 10 5 10, 5, or 2, or by a factor or volume less than 10 100 10 50 10 10 10 5 10 3 10, 1 or 10 -5 Cubic nanometers or cubic centimeters. In some other cases, the volume V2 can be smaller than V1 by an α factor ranging from 1.0001 to 10. 20 1.2 and 10 10 or between 2 and 10 5 Or by a factor or volume between 10 -5 and 10 100 10 -1 and 10 10, or 1 and 10 5 Between cubic nanometers and cubic centimeters.

[0481] In one embodiment of the invention, sound waves or radiation are applied sequentially, preferably to nanoparticles or body parts, when or

[0482] First, applying sound waves or radiation to a region, volume, surface, or length larger than the region, volume, surface, or length containing nanoparticles, and

[0483] Second, regions, volumes, surfaces, or lengths containing nanoparticles absorb sound waves or radiation, resulting in an increase in temperature, or generating anti-tumor activity or destroying body parts, while regions, volumes, surfaces, or lengths excluding nanoparticles contain pathological or tumor cells.

[0484] In another embodiment of the invention, the heating, cooling, dissociation, or non-dissociation steps preferably occur in less than 10 percent. 20 10 10 10 5 10 3 The acoustic or radiation volume is 90, 70, 50, 20, 10, or 1, preferably when the nanoparticle region is included in less than 10%. 20 10 10 10 5 10 3 The acoustic or radiative volume is 90, 70, 50, 20, 10, or 1. These percentages may be: i) the volume in which heating, cooling, dissociation, or non-dissociation steps occur, or ii) the ratio between the volume containing nanoparticles and the acoustic or radiative volume.

[0485] The present invention also relates to acoustic therapy or radiotherapy using sound waves or radiation, preferably sequential, more preferably sequential in space, on nanoparticles or body parts, wherein:

[0486] Applying sound waves or radiation to volume V1,

[0487] Nanoparticles, or body parts, are contained within volume V2.

[0488] And V2 is greater than V1. In some cases, the volume V2 can be larger than V1 by an α factor, which can be greater than 1.0001, 1.1, 1.2, 2, 5, 10, 10 3 10 5 Or 10 20或 By a factor or volume greater than 10 -5 10 -1 1, 5, 10, 10 3 Or 10 5Cubic nanometers or cubic centimeters. In some other cases, the volume V2 can be larger than V1 by an α factor that can be less than 10. 20 10 5 10, 5, or 2, or by a factor or volume less than 10 100 10 50 10 10 10 5 10 3 10, 1 or 10 -5 Cubic nanometers or cubic centimeters. In some other cases, the volume V2 can be larger than V1 by an α factor, which is between 1.0001 and 10. 20 1.2 and 10 10 or between 2 and 10 5 Between or through a factor or volume between 10 -5 and 10 100 10 -1 and 10 10 , or 1 and 10 5 Between cubic nanometers and cubic centimeters.

[0489] In one embodiment of the invention, sound waves or radiation are applied sequentially, preferably to nanoparticles or body parts, when or

[0490] First, applying sound waves or radiation to a region, volume, surface, or length smaller than the region, volume, surface, or length containing nanoparticles, and

[0491] Second, regions, volumes, surfaces, or lengths containing nanoparticles that are not exposed or not subjected to sound waves may generate a temperature increase, or produce antitumor activity or destroy body parts, pathological or tumor cells, preferably through a mechanism in which the effect caused by applying sound waves to the nanoparticles, such as vortices, nanoparticle movement, and temperature increase, is transferred from the nanoparticles exposed to the sound waves to the nanoparticles not exposed to the sound waves.

[0492] In another embodiment of the invention, the heating, cooling, dissociation, or non-dissociation step preferably occurs in greater than 10 percent. -10 10 -5 10 -1 1, 10, 20, 50, 70, 90, 10 3 10 5 10 10 Or 10% 20 The volume of sound waves or radiation, preferably, when the nanoparticle region is included in more than 10% of the sound wave or radiation volume. 20 10 10 10 5 10 3The sound wave or radiation volume is 90, 70, 50, 20, 10 or 1.

[0493] The present invention also relates to acoustic therapy or radiotherapy using sound waves or radiation, preferably sequential, more preferably sequential in space, on nanoparticles or body parts, wherein:

[0494] Applying sound waves or radiation to volume V1,

[0495] Nanoparticles, or body parts, are contained within volume V2.

[0496] V2 is approximately equal to V1. In some cases, the volume V2 can be approximately equal to V1 when it does not differ from V1 by a factor of α, which is greater than 1.0001, 1.1, 1.2, 2, 5, 10, 10. 3 10 5 Or 10 20 Or by a factor or volume greater than 10 -5 10 -1 1, 5, 10, 10 3 Or 10 5 Between cubic nanometers and cubic centimeters.

[0497] In one embodiment of the invention, the heating, cooling, dissociation, or non-dissociation step occurs in the nanoparticle region, or at a concentration greater than 10%. -9 10 -5 10 -3 10 -1 1, 10, 20, 50, 70, 10 9 90 or 99% of the nanoparticle region, preferably not occurring outside of this region. This percentage can be the ratio between the volume of the heating, cooling, dissociation, or non-dissociation step occurring and the volume of the nanoparticle region.

[0498] In one embodiment of the invention, when sound waves or radiation are applied to nanoparticles or body parts, heat, free radicals or reactive species, bubbles, cavitation or cavitation bubbles are generated or produced through the nanoparticles, preferably in nanovolume V2, and preferably not in volume V1, or preferably more in volume V2 than in volume V1, with a preferred pass factor α:i) greater than 1.0000001, 1.1, 1.2, 1.5, 2, 5, 10, 10 in some cases. 3 Or 10 5 ii) less than 10 in some other cases 100 10 50 10 20 10 10 10 5 10 2, 10, 5, 2, 1.2 or 1.000001, iii) in other cases at 1.000001 and 10 100 Between 1.1 and 10 5 between.

[0499] In some cases, volumes V2 and / or V1 can be, or similarly, or replaced by: i) surfaces S2 and / or S1, or ii) lengths L2 and / or L1.

[0500] In one embodiment of the invention, it is preferred that at t i或 During period t3, the applied acoustic wave intensity, acoustic wave power, acoustic wave power density, acoustic wave energy, acoustic wave energy density, radiant energy, radiant energy density, radiant intensity, radiant power, or radiant power density are less than 10. 100 10 50 10 20 10 9 10 6 10 3 , 100, 10, 1, 10 -1 10 -2 Or 10 -5 Tiles or tiles per centimeter or per square centimeter or tiles per cubic centimeter or tiles per second or tiles per second per centimeter or tiles per second per square centimeter or tiles per second per cubic centimeter.

[0501] In one embodiment of the invention, preferably during ti or t3, the acoustic wave intensity, acoustic wave power, acoustic wave power density, acoustic wave energy, acoustic wave energy density, radiant energy, radiant energy density, radiant intensity, radiant power, or radiant power density are applied at a value greater than 10. -100 10 -50 10 -20 10 -9 10 -6 10 -2 , 1, 10, 1 10 2 Or 10 5 Tiles or tiles per centimeter or per square centimeter or tiles per cubic centimeter or tiles per second or tiles per second per centimeter or tiles per second per square centimeter or tiles per second per cubic centimeter.

[0502] In one embodiment of the invention, the frequency of the geosonic waves or radiation applied during ti or t3 is preferably below 10. 100 10 50 10 20 10 10 10 5 10 3 ,10,1,10 -3 10 -6 10-9 Or 10 -20 Gihertz.

[0503] In one embodiment of the invention, preferably, the frequency of the geosonic wave or radiation applied during ti or t3 is greater than 10. 100 10 50 10 20 10 10 10 5 10 3 ,10,1,10 -3 10 -6 10 -9 Or 10 -20 Gihertz.

[0504] In some cases, sound waves or radiation are applied to areas less than 10 -6 10 -3 10 -1 , 1, 10, 10 3 10 6 10 9 Or 10 20 Nanoparticles, or milligrams of nanoparticles per cell or per cubic millimeter of body portion.

[0505] In some cases, sound waves or radiation are applied to areas greater than 10. -6 10 -3 10 -1 , 1, 10, 10 3 10 6 10 9 Or 10 20 Nanoparticles, or milligrams of nanoparticles per cell or per cubic millimeter of body portion.

[0506] In another embodiment of the invention, when sound waves or radiation are applied to nanoparticles or body parts, it produces: i) an increase in temperature of the nanoparticles or body parts, ii) dissociation of compounds from the nanoparticles, iii) cell destruction or growth inhibition, preferably pathological or tumor cells belonging to the body parts, iv) death, destruction, denaturation, volume reduction, or inactivation of biological material preferably belonging to pathological sites or body parts, v) movement or vibration of the nanoparticles, vi) pressure applied to the body parts or nanoparticles, vii) absorption of sound waves or radiation by the nanoparticles, or viii) internalization of the nanoparticles within cells.

[0507] In one embodiment of the invention, the cell destruction or growth inhibition is preferably more than 1, 10, or 10. 3 10 6 10 9 Or 10 20The preferred volume of a cell per cubic millimeter or cubic centimeter of body can be achieved by adjusting or regulating the frequency, intensity, energy, or power of sound waves or radiation.

[0508] In one embodiment of the present invention, sound waves or radiation induce the motion or vibration of nanoparticles when the mass of the nanoparticles is: i) greater than 10 in some cases. -50 10 -5 10 -1 or 1 microgram per nanoparticle or, ii) less than 10 in some other cases. 20 10 10 10 5 10 3 10 2 ,1,10 -3 , or 10 -5 Micrograms per nanoparticle. In this case, sound waves can cause the nanoparticles to move or vibrate more or less than other materials, atoms, ions that are not arranged or assembled in the nanoparticles and preferably surround the nanoparticles.

[0509] In one embodiment of the invention, sound waves or radiation apply pressure to the nanoparticles or body parts, wherein: i) in some cases greater than 10 -9 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 6 Or 10 9 Megapascals, preferably per cubic centimeter of body portion, or ii) less than 10 in some other cases. -9 10 -5 10 -3 10 -1 , 1, 10, 10 3 10 6 Or 10 9 Megapascals, preferably per cubic centimeter of body portion.

[0510] In one embodiment of the invention, nanoparticles preferably absorb sound wave energy more significantly, preferably with a factor of at least 1.1, 2, 5, 10, 25, 50, or 100, compared to other substances, atoms, or ions that are not arranged or assembled, or not contained within, preferably surrounding, or preferably belonging to the body portion of the nanoparticles. In some cases, the temperature rise of the nanoparticles or within the nanoparticle region is at least 10 greater than the temperature rise of other substances or regions outside the nanoparticle region. -9 10 -6 10 -3 1, 2, 5, 10 or 20 degrees Celsius.

[0511] In one embodiment of the invention, the internalization of nanoparticles into cells can be made possible by adjusting and tuning the frequency, intensity, energy, application time, or power of the sound waves or radiation to values ​​different from those in previous embodiments, preferably with more than 10 nanoparticles internalized into cells. -6 10 -3 10 -1 , 1, 10, 10 3 10 6 10 9 , or 10 20 Nanoparticles based on per cell or per cubic millimeter of body part, or milligrams of nanoparticles.

[0512] In one embodiment of the invention, the internalization of nanoparticles within cells can be prevented by adjusting and tuning the frequency, intensity, energy, application time, or power of the sound waves or radiation to values ​​different from those in previous embodiments, preferably with more than 10 nanoparticles internalized. -6 10 -3 10 -1 , 1, 10, 10 3 10 6 10 9 , or 10 20 Nanoparticles based on per cell or per cubic millimeter of body part, or milligrams of nanoparticles.

[0513] In another embodiment of the invention, when sound waves or radiation are applied to nanoparticles or body parts, they do not cause damage to cells, preferably healthy cells, or growth inhibition.

[0514] In one embodiment of the invention, cell destruction or growth inhibition is prevented by adjusting the frequency, intensity, energy, application time, or power of the sound waves or radiation, preferably healthy cells, preferably more than 1, 10, or 10. 3 10 6 10 9 Or 10 20 These cells.

[0515] In one embodiment of the invention, the acoustic medical treatment or its efficacy, or the destruction or treatment or reduction in volume of a tumor, body part, or pathological site, is due to or related to a treatment mechanism, preferably a treatment mechanism related to a treatment mechanism. In some cases, this mechanism preferably occurs when acoustic waves or radiation are applied to nanoparticles or body parts, and preferably does not occur when acoustic waves or radiation are not applied to nanoparticles or body parts.

[0516] In one embodiment of the invention, the mechanism of treatment, preferably at the beginning or initial stage of the mechanism, involves, is attributable to, or is associated with: i) an increase in temperature, preferably in the body or nanoparticles; ii) the generation or production of free radicals or reactive substances, preferably through nanoparticles, such as reactive oxygen species (ROS); iii) the dissociation of compounds from the nanoparticles; iv) preferably due to the pharmaceutical effect produced by the compounds; v) metabolic effects; or vi) cavitation.

[0517] In one embodiment of the invention, cavitation is associated with the generation of bubbles. In some cases, cavitation can induce mechanical stress on cells, preferably the cell membrane, and induce cell death. The size and number of bubbles can be altered in the presence of nanoparticles. They can be increased or decreased by greater than or less than 1.5, 2, 10, 100, or 10. 3 Or 10 9 The factors. In some cases, the size and number of bubbles can tend to approximate the size and number of nanoparticles exposed to sound waves or radiation and / or differ from the size and number of these nanoparticles by less than 10. 9 10 5 10 3 10 2 or a factor of 10

[0518] In another embodiment of the invention, the mechanism of treatment, preferably following or caused by the initiation or activation of such mechanism, involves, is attributed to, or relates to: i) ii) preferably a pathological cell apoptosis mechanism, iii) an indirect mechanism or bystander effect. In some cases, more than 1, 5, 10, 10 [units of measurement missing] occur after the initiation or activation of this mechanism. 3 10 5 Or 10 10 Second.

[0519] In some cases, indirect mechanisms or bystander effects may be involved, attributable to or related to the destruction of pathological cells at a distance from or relative to the nanoparticles or the nanoparticle region, namely: i) in some cases less than 5, 2, 1, 10 -1 10 -3 10 -3 10 -6 Or 10 -9 nanometers, ii) in some other cases, greater than 10 -1 1, 5, 10, 10 3 Or 10 5 nanometers, or iii) in some other cases at 10 -1 and 10 20 Between nanometers, or between 1 and 10 10 Between nanometers, or between 1 and 105 Between nanometers

[0520] In some cases, the therapeutic mechanism may involve, due to or related to the direct effects of the nanoparticles, preferably excluding immune effects or bystander effects, or some effect that can induce the destruction of pathological or tumor cells, or reduce the volume of a part of the body, at a certain distance from the nanoparticles, preferably at a distance greater than 1, 10, or 10. 3 10 5 10 10 10 20 10 50 Or 10 100 nanometer.

[0521] In one embodiment of the invention, preferably, during at least one sequence or treatment course, the treatment mechanism is i) activated by the initial application of sound waves or radiation, ii) reactivated by reapplication of sound waves or radiation, or iii) deactivated by stopping the application of sound waves or radiation after activation or reactivation.

[0522] In one embodiment of the invention, the radiation, sound wave, and nanoparticle parameters are: i) the power, intensity, force, frequency, and energy of the sound wave or radiation; ii) the volume or body part exposed to the sound wave or radiation; iii) the duration of application of the sound wave or radiation; and iv) times t1, t2, or t... 3， v) the duration of the sequence or treatment, vi) the time between the two sequences or treatments, and / or vii) nanoparticle properties such as concentration, tissue, distribution, size, and composition.

[0523] In some other cases, the radiation, acoustic, and nanoparticle parameters are adjusted, fixed, optimized, sufficiently long or large, sufficiently small or low, or set at specific values ​​selected to achieve at least one of the following therapeutic parameters, preferably the desired therapeutic parameters: i) the therapeutic mechanism, ii) the desired or a certain level of cavitation, (iii) the desired or a certain level or concentration of free radicals or reactive substances such as free radical oxygen species (ROS), iv) the desired or a certain level of apoptosis or apoptotic cell levels, v) the required or a certain temperature during the heating step, vi) vii) the desired or a certain temperature during the cooling step, viiii) the desired or a certain percentage of dissociated compounds during the non-dissociation step.

[0524] In one embodiment of the invention, the desired therapeutic parameters are the therapeutic parameters that are desired to be achieved during treatment. In some cases, these differ from therapeutic parameters achieved by applying sound waves or radiation to nanoparticles or body parts by less than 10%. -20 10 -10 10-5 10 -3 10 -1 1, 5, 10, 50, 100, 10 4 10 5 Or 10 10 In some other cases, the therapeutic parameters differ from those achieved by applying sound waves or radiation to nanoparticles or body parts by more than 10%. -20 10 -10 10 -5 10 -3 10 -1 1, 5, 10, 50, 100, 10 4 10 5 Or 10 10 In some other cases, this percentage can be the ratio between the desired therapeutic parameter and the therapeutic parameter achieved by applying sound waves or radiation to nanoparticles or body parts.

[0525] In some cases, during time t1, at least one treatment parameter may be higher or greater by a factor than during t2 or t3, preferably at least equal to 1, 1.2, 1.5, 2, 5, 10, or 10. 2 10 3 10 5 10 9 Or 10 20 .

[0526] In some cases, cavitation may be or is associated with bubbles or cavitation bubbles.

[0527] In other cases, free radicals, reactive substances, or bubbles may associate with or be the compound.

[0528] In other cases, free radicals, reactive substances, or bubbles are not compounds.

[0529] In some cases, the desired temperature during the heating step can be greater than or equal to 0, 5, 10, 25, 30, 37, 39, 41, 45, 50, 100, or 10 °C. 3 Or 10 5 °C.

[0530] In some other cases, the desired temperature during the heating step can be below 10°C. 5 10 3 , 100, 50, 45, 41, 39, 37, 30, 25, 30 or 37 °C.

[0531] In some other cases, the required temperature during the heating step can be between -273 and 10. 100 and 10 3 Or between 10 and 100 degrees Celsius.

[0532] In one embodiment of the invention, the desired temperature range is 41 degrees Celsius to 100 degrees Celsius, wherein the degrees Celsius is preferably the minimum value that can trigger therapeutic effects such as antitumor activity, and 100 degrees Celsius is the boiling point of water, which in some cases preferably constitutes a large portion of the body part. The minimum value of this range (41 degrees Celsius) can be reduced, for example, to greater than 1, 5, 10, 50, 100, 150, 200, or 250 degrees Celsius, for example, when the body part is cooled. In some other cases, the maximum value of this range (100 degrees Celsius) can be increased, for example, to greater than 1, 5, 10, 50, 10 ... 3 , or 10 5 Celsius, for example when the body part does not primarily consist of water or when the body part is heated, or when the intensity or frequency of the sound wave is increased, or when the concentration of magnetosomes or nanoparticles is increased.

[0533] In some cases, the expected percentage of the compound dissociated in the dissociation step can be greater than 0.1%, 1%, 5%, 10%, 25%, 50%, 75%, or 90%.

[0534] In some other cases, the expected percentage of the compound dissociated during the dissociation step may be less than 100%, 90%, 75%, 50%, 25%, 10%, 5%, 1%, or 0.1%.

[0535] In other cases, the expected percentage of the compound dissociated during the dissociation step can be between 0 and 100%, 0.1 and 99%, or 5 and 75%.

[0536] In some cases, the desired temperature during the cooling step is greater than 10°C below the temperature of the heating step. -5 1, 5, 10 3 Or 10 5 Celsius.

[0537] In some other cases, the desired temperature during the cooling step is 10°C lower than the temperature during the heating step. 5 10 3 5, 1 or 10 -5 Celsius.

[0538] In some cases, the desired percentage of dissociation of the compound is greater than 0.001, 0.01, 0.1, 1, 2, 5, 10, 25, 50, 75, 80, 90 or 99 percent.

[0539] In some other cases, the desired percentage of dissociation of the compound is less than 100, 90, 80, 75, 50, 25, 10, 5, 2, 1, 0.1, 0.01, or 0.001 percent.

[0540] In one embodiment of the invention, the compound that reaches a desired temperature during the heating step or a desired level of dissociation during the dissociation step is possible, preferably by increasing, through a factor β, preferably between time t2 or t3 and time t1: i) the power, intensity, force, frequency, and energy of the sound wave or radiation, ii) the volume or body part exposed to the sound wave or radiation, iii) the duration of the sound wave or radiation, and / or iv) the concentration of nanoparticles.

[0541] In one embodiment of the invention, the compound that reaches a desired temperature during the heating step or a desired level of dissociation during the dissociation step, which may be achieved by reducing, preferably by a factor β, preferably between time t1 and time t2 or t3: i) the power, intensity, force, frequency, and energy of the sound wave or radiation, ii) the volume or body part exposed to the sound wave or radiation, and / or iii) the duration of the application of the sound wave or radiation.

[0542] In some cases, β can be greater than 1.00001, 1.0001, 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 10. 3 10 5 10 10 10 20 Or 10 40 ,

[0543] In some other cases, β can be less than 10. 50 10 20 10 10 10 5 10 3 , 10, 5, 2, 1.5, 1.2, 1.1, 1.01, 1.001, 1.000 or 1.00001,

[0544] In several other cases, β can be between 1.00001 and 10. 50 1.1 and 10 5 Between, or 1.2 and 10 3 between.

[0545] The present invention also relates to nanoparticles for use in acoustic therapy or radiotherapy or for treating parts of an individual body, wherein said treatment involves or includes at least one of the following steps:

[0546] The preparation of suspensions or compositions of nanoparticles preferably has sufficiently high stability and concentration (step 1).

[0547] Apply nanoparticles to parts of the body or to an individual (step 2).

[0548] - Target the body part (step 3).

[0549] Detection or imaging of nanoparticles (step 4).

[0550] The detection or imaging of body parts preferably includes nanoparticles (step 5).

[0551] Apply sound waves or radiation to the nanoparticles (step 6).

[0552] Removing body parts is preferably done surgically (step 7).

[0553] Treatment of the body parts uses methods different from sound wave or radiation therapy, such as surgery or chemotherapy (step 8).

[0554] In one embodiment of the invention, temperature, preferably in the body part or nanoparticles, is measured during steps 1 to 8, preferably during step 6, before or after.

[0555] In one embodiment of the invention, steps 1 to 8 follow each other in the indicated order or in any other order.

[0556] In one embodiment of the invention, the preferred treatment method in step 4 or 5 includes imaging a body part, preferably following the evolution or growth of the body part after treatment, preferably using magnetic resonance imaging, computed tomography (CT), a scanner, positron emission tomography (PET), radiography, or ultrasound imaging. The concentration of nanoparticles may be too high in some cases to enable effective imaging of the body part. Nanoparticles may act as a screen or obscure body parts in some cases, preventing effective imaging of the body parts. In some cases, the composition of the nanoparticles is adjusted or changed to enable imaging of the body part. To enable imaging of the body part or treatment, in some cases the following measures may be taken: i) the iron oxide composition is replaced by another composition comprising lithium, beryllium, scandium, titanium, vanadium, chromium, manganese, iron, nickel, copper, zinc, boron, carbon, nitrogen, oxygen, fluorine or helium, or alkaline earth metals, minting metals, or trill or tretrela or pentel or phosgene, sulfides or halogens or rare gases, or ii) the concentration of nanoparticles is reduced, preferably below 10. -20 10 -9 10 -6 10 -3 10-1 , 1, 10, 10 3 10 6 10 9 Or 10 20 Milligrams per cubic centimeter or milligrams per cubic centimeter of body part.

[0557] Preferably, the radiation or sound waves according to the invention generate free radicals or reactive substances, especially when they are applied to nanoparticles or magnetic particles.

[0558] The present invention also relates to nanoparticles for use, wherein the sequential application of sound waves or radiation to a body part or nanoparticles prevents a decrease in temperature of the body part or nanoparticles.

[0559] In one embodiment of the invention, when sound waves or radiation are applied to a body part or nanoparticles, they prevent a decrease in temperature. Preferably, the sequential application of sound waves or radiation prevents a decrease in temperature under conditions of the applied nanoparticle concentration, the frequency, power, and / or energy, while the continuous application of sound waves or radiation does not prevent such a decrease in temperature.

[0560] In some cases, the magnitude of the prevented temperature drop can be greater than 0.10. -50 10 -20 10 -10 10 -5 10 -1 1, 5, 10 or 10 2 Temperature in degrees Celsius, preferably measured per minute, per cubic centimeter of body part, or per gram of nanoparticles.

[0561] In some other cases, the magnitude of the prevented temperature drop can be less than 10. 50 10 20 10 10 10 5 10 2 , 10, 5, 2, 1, 10 -1 Or 10 -2 °C, preferably measured per minute, per cubic centimeter of body portion, or per gram of nanoparticles.

[0562] In some other cases, the magnitude of the prevented temperature drop can be 10. -50 and 10 50 10 -20 and 10 20 10 -10 and 10 10 or between 10 -3 and 10 3Between degrees Celsius, preferably measured per minute, preferably per cubic centimeter of body portion or per gram of nanoparticles.

[0563] For a magnetosome concentration of 500 micrograms per milliliter, sequential exposure to sound waves with a power of 100 watts per square centimeter over 12 minutes can prevent a suitable temperature drop of ~2 degrees Celsius. Greater protection against temperature drop can be achieved by increasing: i) the magnetosome concentration to above 500 micrograms per milliliter, ii) the sound wave frequency to above 1 MHz, and / or iii) the sound wave power to above 100 milliwatts per square centimeter.

[0564] The present invention also relates to nanoparticles used according to the invention, wherein the application of sound waves or radiation to the nanoparticles generates or produces free radicals or reactive substances.

[0565] This invention also relates to a method for generating reactive or free radical-like substances through nanoparticle or sonic medical treatment, wherein:

[0566] i) Radiation or sound waves are applied sequentially to the nanoparticles.

[0567] ii) Nanoparticle degradation, and / or

[0568] iii) Nanoparticles are magnetic bodies

[0569] In some cases, when nanoparticles are dissolved, decomposed, and / or desorbed, the nanoparticles are preferably disposed of through cells, body parts, organelles, or lysosomes.

[0570] The present invention also relates to acoustic or radiation-based medical treatments according to the invention, for generating reactive or free radical substances from nanoparticles.

[0571] In some cases, acoustic therapy or radiotherapy may be, or may include, a method for generating reactive or free radical species from nanoparticles. In one embodiment of the invention, the reactive or free radical species are superoxide, oxygen radicals, hydroxyl groups, alkoxy groups, peroxy groups, nitric oxide, nitric oxide, and nitrogen dioxide.

[0572] In one embodiment of the invention, the reactive or free radical substance is associated with, derived from, or generated by hydrogen peroxide. In some cases, the reactive or free radical substance may be a derivative of hydrogen peroxide, resulting from the conversion of hydrogen peroxide, or from a chemical reaction involving hydrogen peroxide.

[0573] In one embodiment of the invention, the free radicals or reactive substances are free when separated or dissociated from the nanoparticles. In some cases, the free radicals or reactive substances are compounds that preferably dissociate from the nanoparticles when radiation or sound waves are applied to the nanoparticles or body parts.

[0574] In one embodiment of the invention, the generation or production of free radicals or reactive substances, preferably by nanoparticles, is associated with or results from or produces: i) the efficacy of sonic medicine therapy, ii) the destruction of body parts, and / or iii) the reduction of the volume of the main body.

[0575] In one embodiment of the invention, reactive or free radical substances are preferably generated or produced by nanoparticles. Preferably, when radiation or sound waves are applied to the nanoparticles, it is due to or associated with: i) degradation of the nanoparticles, preferably degradation of biological materials, cells, or organelles; ii) reduction in nanoparticle size, preferably by more than 10%. -5 10 -3 The percentage can be 1, 5, 10, 50, or 75 or more, where the percentage can be the ratio between the size of the nanoparticles after the sound wave medical treatment and the size of the nanoparticles before the sound wave medical treatment, preferably decreasing from a size greater than 1, 5, 10, 50, 75, or 100 nanometers before the medical treatment to less than 10 nanometers after the sound wave treatment. 5 10 3 10 2 (iii) the size of 50, 20, 10, 5, 2 or 1 nanometer, or (iii) generated or released or dissociated from nanoparticles of a compound or free ions such as free oxygen, nitrogen or iron ions.

[0576] The present invention also relates to the generation of reactive or free radical substances, or to sonic medicine treatment, or to radiation medicine treatment, for: i) treating diseases comprising radiation-resistant or sonic-resistant cells, ii) the destruction or death of at least one radiation-resistant or sonic-resistant cell, preferably contained in a body part, or iii) the reduction in the volume of a body part.

[0577] In some cases, radiation-resistant cells can be cells that are not destroyed when irradiated in the absence of nanoparticles, but are destroyed when irradiated in the presence of nanoparticles, wherein the same or similar radiation, radiation power, radiation intensity and / or radiation frequency are applied to the nanoparticles or body parts, thereby preferably making it feasible to cause cell destruction or death in comparison between the presence and absence of nanoparticles.

[0578] In some cases, acoustically resistant cells can be cells that are not destroyed when acoustic waves are applied to them in the absence of nanoparticles, but are destroyed when acoustic waves are applied to them in the presence of nanoparticles, wherein the same or similar radiation, radiation power, radiation intensity and / or radiation frequency are applied to the nanoparticles or body parts, thereby preferably making it feasible to cause cell destruction or death in comparison between the presence and absence of nanoparticles.

[0579] The present invention also relates to a method for generating free radicals or reactive substances or acoustic medical treatments, wherein the free radicals or reactive substances are:

[0580] i) Destroying pathological cells, tumor cells, bacteria, viruses, or pathological sites, and / or

[0581] ii) Do not damage healthy cells, non-pathological cells, non-tumor cells, cells in healthy sites or belonging to healthy individuals.

[0582] The present invention also relates to nanoparticles used according to the invention, wherein the nanoparticles induce destruction of pathological sites in a body part without destroying, preferably, a healthy site surrounding the pathological site.

[0583] In some cases, nanoparticles can induce greater than 1, 10, 10 3 10 6 10 9 Or 10 15 The destruction of pathological cells and / or less than 1, 10, 10 3 10 6 10 9 Or 10 15 Healthy cells.

[0584] In some cases, free radicals or reactive substances can produce oxidative stress, preferably causing cell damage or death, preferably causing pathological cells, preferably causing tumor cells, bacteria or viruses.

[0585] The present invention also relates to a method for generating free radicals or reactive substances or to sound wave medical therapy, wherein the amount or concentration of free radicals or reactive substances generated or produced by nanoparticles is more significant when radiation or sound waves are sequentially applied to nanoparticles or body parts than when radiation or sound waves are continuously applied to nanoparticles or body parts, preferably by a factor α, which in some cases may be greater than or equal to: i) 1.0001, 1.1, 1.2, 1.5, 2, 5, 10 or 10 3 ii) 1, 2, 5, 10, 10 3 10 5 10 10 Or 10 50iii) 10 free radicals or reactive substances per cubic centimeter of body part or per gram of nanoparticles -100 10 -50 10 -20 10 -10 10 -5 10 -3 10 -1 1, 2, 5, 10, 10 3 10 5 10 10 Or 10 50 Micromolar amounts of free radicals or reactive substances. This can be when the application of radiation or sound waves significantly increases the amount of free radicals or reactive substances generated or produced by the nanoparticles, for example by catalysis or promotion or enabling of the Fenton or Heber-Weiss reaction, or derived from the dissociation of ions from the nanoparticles, such as iron or oxygen ions. In some other cases, the factor α may be less than or equal to: i) 10 100 10 10 10 5 10 3 , 10, 5, 3 or 2, or ii) 10 100 10 50 10 20 10 10 10 5 10 2 10 or 5 free radicals or reactive substances per cubic centimeter of body part or per gram of nanoparticles, or, iii) 10 100 10 50 10 20 10 10 10 5 ,10,10 -5 Or 10 -10 Micromolar amounts of free radicals or reactive substances. This can be the case where the application of radiation or sound waves to nanoparticles does not change or increase the amount of free radicals or reactive substances generated or produced by the nanoparticles.

[0586] In another embodiment of the invention, the amount or concentration of free radicals or reactive substances generated or produced by the nanoparticles is preferably less significant when radiation or sound waves are sequentially applied to the nanoparticles or body parts than when radiation or sound waves are continuously applied to the nanoparticles or body parts. A factor α is preferred, and in some cases, factor α may be greater than or equal to: i) 1.0001, 1.1, 1.2, 1.5, 2, 5, 10, or 10. 3 , or ii) 1, 2, 5, 10, 10 3 105 10 10 Or 10 50 Free radicals or reactive substances per cubic centimeter of body part or per gram of nanoparticles, or iii) 10 -100 10 -50 10 -20 10 -10 10 -5 10 -3 10 -1 1, 2, 5, 10, 10 3 10 5 10 10 Or 10 50 Micromolar amounts of reactive or free radical substances. This can be when the application of radiation or sound waves significantly reduces the amount of free radicals or reactive substances, such as iron or oxygen ions, originating from the nanoparticles, for example, by preventing the dissociation or departure of these substances from the nanoparticles. In some other cases, the factor α can be less than or equal to: i) 10 100 10 10 10 5 10 3 , 10, 5, 3 or 2, or ii) 10 100 10 50 10 20 10 10 10 5 10 2 10 or 5 free radicals or reactive substances per cubic centimeter of body part or per gram of nanoparticles, or, iii) 10 100 10 50 10 20 10 10 10 5 ,10,10 -5 or 0 -10 Micromolar amounts of free radicals or reactive substances. This is the case when the application of radiation or sound waves to nanoparticles does not change or more moderately reduces the amount of free radicals or reactive substances generated by or produced by the nanoparticles.

[0587] The present invention also relates to a method for generating free radicals or reactive substances or for use in acoustic medical therapy, wherein the nanoparticles have at least one of the following properties:

[0588] Surface area to volume ratio greater than 10 -50 per nanometer,

[0589] A composition or chemical formula containing the following components: i) atoms having at least two different stoichiometric coefficients or oxidized or reduced states, such as Fe. 2+ and Fe 3+ ii) Ions with different numbers of charges or oxidized or reduced states, such as Fe 2+ and Fe 3+ iii) Atoms lead to the formation of at least two different types of ions with different amounts of charge, in oxidized or reduced states, such as Fe. 2+ and Fe 3+ ,

[0590] The composition and / or size and / or surface / volume ratio are capable of causing or resulting in a Fenton or Heber-Weiss reaction.

[0591] Dissolution, decomposition, or decrystallization, preferably promoting reactions originating from or dissociating from nanoparticles.

[0592] Chain-like arrangement, and / or

[0593] The concentration in the body portion is less than 1 mg / cm³ or 1 mg / cell or 1 mg / cm³ of body portion.

[0594] At least one of these properties preferably results in a greater amount or concentration of free radicals or reactive substances generated when radiation or sound waves are applied to the nanoparticles than when no radiation or sound waves are applied, preferably exceeding 1.0001, 1.1, 1.5, 2, 5, 10, 10 3 Or 10 5 Factors.

[0595] In one embodiment of the present invention, the nanoparticles have a large surface area to volume ratio, preferably greater than 10. -100 10 -50 10 -20 10 -10 10 -5 10 -3 10 -1 The surface area to volume ratio of a nanoparticle is 1, 5, 10, or 100 per nanometer. A sufficiently large surface area to volume ratio allows a greater number of atoms on the nanoparticle surface to be exposed to radiation or sound waves, where these atoms can preferably react to form free radicals or reactive substances. Preferably, atoms located in or inside the nanoparticle are less likely to generate free radicals or reactive substances than atoms located on the nanoparticle surface.

[0596] In another embodiment of the invention, the surface-to-volume ratio of the nanoparticles is small, preferably less than 10. 100 10 50 10 20 10 10 105 10 3 , 10, 5, 2, 1, 10 -5 10 -10 10 -20 Or 10 -50 For each nanometer, the surface area to volume ratio of the nanoparticle can be desired to enable the nanoparticle to maintain a three-dimensional volume or geometry and / or prevent the nanoparticle from switching from a three-dimensional system to a two-dimensional system and / or enable the nanoparticle to absorb or interact with radiation or sound waves, wherein the absorption or interaction of radiation or sound waves is more significant for a three-dimensional system than for a two-dimensional system.

[0597] In another embodiment of the invention, the surface-to-volume ratio of the nanoparticles includes 10. -5 per nanometer and 10 3 per nanometer or between 10 -2 per nanometer and 1 per nanometer.

[0598] In one embodiment of the invention, the composition of the general chemical formula of the nanoparticles comprises at least one atom A, having at least two different coefficients or stoichiometric coefficients α, wherein α can be equal to 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, an integer, or a decimal number.

[0599] In one embodiment of the invention, the nanoparticles induce a Fenton reaction. In some cases, the Fenton reaction can be written as: i) Fe 2+ + H2O2 ----> Fe 3+ + •OH + OH - , and / or, ii) Fe 3+ + H2O2 ----> Fe 2+ + •OOH + H + In some cases, the Fenton reaction is: i) iron (II) is oxidized to iron (III) by hydrogen peroxide, forming hydroxyl and hydroxide ions in the process, and / or ii) iron (III) is reduced back to iron (ii) by another molecule of hydrogen peroxide, forming a hydroxyl radical and a proton. In some cases, the Fenton reaction is promoted or enhanced or made possible by: i) the nanoparticles or the nanoparticles having the chemical formula Fe2, Fe 2+ Fe3+, and / or Fe 3+ Ions or atoms, ii) nanoparticles including malachite and magnetite, or iii) in some other cases, radiation or sound waves are applied to nanoparticles or body parts, and the Fenton reaction produces free radicals or reactive substances.

[0600] In one embodiment of the invention, the nanoparticles cause or undergo a Heber-Weiss reaction, which in some cases can be written as: Fe 3+ + •O2 − → Fe 2+ + O2, Fe 2+ + H2O2 → Fe 3+ + OH − + •OH, and / or •O2 − +H₂O₂ → •OH + OH − + O2.

[0601] In some cases, the Heber-Weiss or Fenton reaction produces •OH (hydrogen peroxide) and / or •OOH (hydrogen peroxide radical) and / or H2O2 (hydrogen peroxide) and / or superoxide (•O2). − In some cases, the reaction is catalyzed by nanoparticles or iron catalysts containing or derived from nanoparticles.

[0602] In one embodiment of the invention, the dissolution of the nanoparticles is a loss of part or all of their mass; preferably, the reduction in mass of the nanoparticles is greater than 10%. -50 10 -10 10 -1 , 1, 5, 10, 5, 0, 75 or 90, where the percentage can be the ratio between the mass of the dissolved nanoparticles and the mass of the nanoparticles before dissolution.

[0603] In another embodiment of the invention, the decomposition of the nanoparticles is a partial or complete change in the composition of the nanoparticles; preferably, the change in the composition of the nanoparticles is greater than 10%. -50 10 -10 10 -1 , 1, 5, 10, 50, 75 or 90, where the percentage can be the ratio between the volume or number of atoms of the nanoparticle and the total volume or number of all atoms of the nanoparticle.

[0604] In one embodiment of the invention, decrystallization of nanoparticles refers to the partial or complete loss of crystallinity, crystal faces, or ordered atomic arrangement of nanoparticles, or the transformation of nanoparticles from a crystalline structure to an amorphous structure, preferably involving a loss of more than 1, 10, or 10 in the nanoparticles. 3 Or 10 5 The crystal planes. In some cases, the loss of at least one crystal plane can be observed using an electron microscope or a device capable of obtaining information similar to that of an electron microscope.

[0605] The present invention also relates to methods for generating free radicals or reactive substances or for use in acoustic or radiological medicine treatments, wherein:

[0606] First: At time t1, radiation or sound waves are applied to the nanoparticles until a certain number of free radical species are reached (step 11). Second: During time t2, radiation or sound waves are not applied to the nanoparticles to reduce the amount of free radicals or reactive substances generated compared to step 1 (step 2). Third: Optionally, steps 1 and 2 are repeated more than twice, and / or

[0607] Radiation or sound waves applied to nanoparticles or body parts locally generate or produce free radicals or reactive substances around the nanoparticles, wherein such local generation or production of free radicals or reactive species can preferably be achieved by: a) low concentration of nanoparticles, preferably less than 10 50 10 20 10 5 10 3 , 10, 5, 2, 1, 10 -2 Or 10 -5 1) gram of nanoparticles per cubic centimeter of body portion, or ii) using nanoparticles that occupy a portion of the body or a cell, such as a lysosome, in which reactive or free radical species can be generated.

[0608] The present invention also relates to methods for generating free radicals or reactive substances or for use in acoustic or radiotherapy, wherein the amount of free radicals or reactive substances generated or produced by the nanoparticles is preferably greater than: i) 1, 2, 5, 10, 10 3 10 5 10 10 Or 10 50 Each free radical or reactive substance per nanoparticle or per gram of nanoparticle, per cubic centimeter of body portion, or per atom of free radical or reactive substance is preferably contained in the surface or nanoparticle, ii) 10 -50 10 -20 10 -10 10 -5 1, 5, 10, 10 3 10 5 Or 10 10 Nanomolar or micromolar free radicals or reactive substances per gram of nanoparticles or micromolar free radicals or reactive substances per cubic centimeter of body fraction, or iii) 10 -50 10 -20 10 -10 10-5 1, 5, 10, 10 3 10 5 or 10 10 Nanomolar or micromolar amounts of free radicals or reactive substances per watt, or molar or micromolar amounts of free radicals or reactive substances per watt per gram of nanoparticles, or nanomolar or micromolar amounts of free radicals or reactive substances per gray, or nanomolar or micromolar amounts of free radicals or reactive substances per gray per cubic centimeter of body part, or nanomolar or micromolar amounts of free radicals or reactive substances per gram of nanoparticles. In some cases, the generation of free radicals or reactive substances may be very large, preferably when the nanoparticles can dissolve in free ions, or when the Fenton or Heber-Weiss reaction can occur, or when the surface area and / or activity of the nanoparticles is large enough to generate these substances.

[0609] In some cases, the free radical or reactive substance may be H2O2.

[0610] This invention also relates to a method for generating free radicals or reactive substances, or to acoustic or radiological medical treatments, wherein the quantity or concentration of free radicals or reactive substances is preferably generated or produced by nanoparticles, and is less than: i) 10 100 10 50 10 20 10 10 10 5 10 3 10, 5, 2 or 1 free radical or active substance per nanoparticle or free radical or active substance per gram of nanoparticle or free radical or active substance per gram of nanoparticle body portion or free radical or active substance per cubic centimeter of body portion or free radical or active substance per nanoparticle per cubic centimeter of body portion or free radical or active substance per atom preferably contained on the surface of the nanoparticle ii) 10 100 10 50 10 20 10 10 10 5 10 2 , 10, 5, 2, 1, 10 -1 10 -3 Or 10 -5 Nanomolar or micromolar free radicals or reactive substances per gram of nanoparticles or per cubic centimeter of body fraction, or iii) 10 100 10 50 10 20 10 10 10 5 103 10, 5, 2, 1 or 10 -3 Nanomolar or micromolar amounts of free radicals or reactive substances per watt, or molar or micromolar amounts of free radicals or reactive substances per watt per gram of nanoparticles, or nanomolar or micromolar amounts of free radicals or reactive substances per gray, or nanomolar or micromolar amounts of free radicals or reactive substances per gray per cubic centimeter of body portion, or nanomolar or micromolar amounts of free radicals or reactive substances per gram of nanoparticles. In some cases, the generation of free radicals or reactive substances can be low, preferably when the nanoparticles cannot dissolve into free ions, when the Fenton or Heber-Weiss reaction cannot occur, or when the surface of the nanoparticles is not large enough and / or reactive enough to allow the generation of these substances.

[0611] In one embodiment of the invention, the preferred amount or concentration of free radicals or reactive substances generated or produced by the nanoparticles is: i) between 1 and 10. 100 10 and 10 50 or between 10 3 and 10 20 The free radical or active substance per nanoparticle or per gram of nanoparticle or per cubic centimeter of body portion or per atom of free radical or active substance preferably contained on the surface of the nanoparticle, ii) between 10 -100 and 10 100 10 -50 and 10 50 10 -10 and 10 10 1 and 10 10 , or 1 and 10 5 Nanomolar or micromolar free radicals or reactive substances per gram of nanoparticles or per cubic centimeter of body fraction, or iii) 10 -100 and 10 100 10 -50 and 10 50 10 -10 and 10 10 1 and 10 10 or between 1 and 10 5 Nanomolar or micromolar free radicals or reactive substances per watt or molar or micromolar free radicals or reactive substances per watt per gram of nanoparticles or nanomolar or micromolar free radicals or reactive substances per gray or nanomolar or micromolar free radicals or reactive substances per gray per cubic centimeter of body part or nanomolar or micromolar free radicals or reactive substances per gram of nanoparticles.

[0612] In one embodiment of the invention, the quantity or concentration of free radicals or reactive substances is measured, which may: i) be the same as or similar to the actual quantity or concentration of free radicals or reactive substances generated or produced by the nanoparticles in a first case, and ii) be different from the actual quantity or concentration of free radicals or reactive substances generated or produced by the nanoparticles in a second case. The second case may occur when the reactive or free radical substance has a short lifetime, reacts and is located in an undetectable position, is too small or too large to be detected, reacts with, interacts with, or is absorbed by some compound.

[0613] This invention also relates to methods for generating free radicals or reactive substances or for use in sound wave medicine or radiation medicine therapy, by:

[0614] i) In some cases, it is preferable to increase the temperature of the nanoparticles or body parts by 10°C. -10 10 -5 10 -1 1, 5, 10, 100 or 10 3 Above 10 degrees Celsius. In some other cases, the temperature rise is preferably below 10 degrees Celsius. 10 10 5 10 3 10 2 10, 5, 2, or 1 degree Celsius; in other cases, the temperature rise should be between 10 and 10 degrees Celsius. -10 and 10 10 10 degrees Celsius -5 and 10 5 Celsius, 10 -3 and 10 3 Celsius, or between 10 degrees Celsius -1 and 10 3 Celsius

[0615] ii) Increase the mobility of nanoparticles, preferably by greater than 10 in some cases. -100 10 -50 10 -20 10 -10 10 -5 10 -1 1, 5, 10, 10 2 10 3 Or 10 5 nanometers per second, and in some other cases less than 10 100 10 50 10 20 10 10 10 5 , 10, 5, 2, 1, 10 -1 10 -3 Or 10-5 Nanometers per second, and in some other cases, by including 10 -100 and 10 100 10 -50 and 10 50 10 -5 and 10 5 10 -1 and 10 3 or between 10 -1 and 10 nanometers per second, and / or

[0616] iv) Dissociation of compounds from nanoparticles

[0617] The present invention also relates to a method for generating free radicals or reactive species by applying sound waves or radiation or performing sound wave or radiotherapy on nanoparticles, wherein the free radical oxygen species preferably destroy at least pathological cells without destroying at least one healthy cell.

[0618] The present invention also relates to a composition, preferably a pharmaceutical composition, comprising at least one nanoparticle as defined herein, which optionally associates with a pharmaceutically acceptable mediator.

[0619] In one embodiment, the carrier is the compound.

[0620] The present invention also relates to a pharmaceutical composition wherein the pharmaceutically acceptable carrier is the compound.

[0621] The present invention also relates to a diagnostic composition comprising at least one nanoparticle as defined herein.

[0622] The present invention also relates to a medical device comprising at least one nanoparticle as defined herein.

[0623] The present invention also relates to a medical device comprising at least one nanoparticle associated with or bound to the compound.

[0624] The present invention also relates to compositions comprising nanoparticles according to the invention optionally associated with or combined with the compound, medical devices, pharmaceutical or cosmetic compositions.

[0625] The present invention also relates to a small magnetic iron for treating anemia, preferably iron-deficiency anemia.

[0626] The present invention also relates to acoustic or radiomedical treatments for generating reactive or free radical species, or as methods for generating reactive or free radical species.

[0627] This invention also relates to a treatment method in sound wave medicine or radiation medicine, comprising the following steps:

[0628] i) Reduce the cell density of parts of the body or tumors, and / or

[0629] ii) Reduce the volume of body parts,

[0630] The method preferably enables the application of nanoparticles to a body part. In yet another embodiment of the invention, the properties or features described in each individual embodiment or section or sentence of this patent application, preferably nanoparticles or methods or treatments, can be combined to produce properties or features, preferably nanoparticles or methods or treatments.

[0631] In another embodiment of the invention, when an entity such as a compound, substance, nanoparticle, radiation has a property with a value of P1 that is higher, longer, or greater than a property with a value of P2 by a factor of α, it means that: P1 = α.P2 (α>1) or P1 = α+P2.

[0632] In another embodiment of the invention, when an entity such as a compound, substance, nanoparticle, or radiation has a property with a value of P1 that is lower, smaller, or shorter than a property with a value of P2 by a factor α, it means that: P1 = αP2 (α < 1), P1 = P2 / α (α > 1), P1 = P2 - α, or P1 = α - P2.

[0633] The present invention will be further described with reference to the following non-limiting drawings and embodiments. Attached Figure Description

[0634] Figure 1: (a) Nanoparticles (magnetic bodies or sigmata) containing 210 µg of iron were inserted into a 4.6 cubic centimeter tissue exposed to ultrasound at a frequency of 3 MHz and a power of 0.5 W / cm². ΔT is specified as the temperature difference between the measured temperature of the tissue or body containing the nanoparticles and the measured temperature of the tissue or body without the nanoparticles, as a function of the duration of the ultrasound application (in minutes). (b) Same as (a) for an ultrasound power of 1 W / cm². (c) Same as (a) for an ultrasound power of 1.5 W / cm².

[0635] Figure 2: (a) For a magnetic particle containing 100 micrograms of iron dispersed in 100 μL of water, exposed to ultrasound at 3 MHz and power levels of 0.5, 1, and 1.5 W / cm², ΔT is specified as the temperature difference between the measured temperature of the magnetic particle dispersed in the water and the measured temperature of the water without the magnetic particle, as a function of the duration of ultrasound application (in minutes). (b) For a sigma nanoparticle containing 100 micrograms of iron dispersed in 100 μL of water, exposed to ultrasound at 3 MHz and power levels of 0.5, 1, and 1.5 W / cm², ΔT is specified as the temperature difference between the measured temperature of the sigma nanoparticle dispersed in 100 μL of water and the measured temperature of 100 μL of water without the sigma nanoparticle, as a function of the ultrasound application time (in minutes). (c) For SPION50 nanoparticles containing 100 micrograms of iron dispersed in 100 microliters of water, exposed to ultrasound at 3 MHz and power levels of 0.5, 1, and 1.5 W / cm², ΔT is defined as the temperature difference between the measured temperature of the SPION50 nanoparticles dispersed in 100 microliters of water and the measured temperature of 100 microliters of water without SPION50 nanoparticles, as a function of the ultrasound application time (in minutes). (d) For SPION100 nanoparticles containing 100 micrograms of iron dispersed in 100 microliters of water, exposed to ultrasound at 3 MHz and power levels of 0.5, 1, and 1.5 W / cm², ΔT is defined as the temperature difference between the measured temperature of the SPION100 nanoparticles dispersed in 100 microliters of water and the measured temperature of 100 microliters of water without SPION100 nanoparticles, as a function of the ultrasound application time (in minutes). (e) For SPION20 nanoparticles containing 100 micrograms of iron dispersed in 100 microliters of water, exposed to ultrasound at 3 MHz and power of 0.5, 1 and 1.5 W / cm², ΔT is specified as the temperature difference between the measured temperature of the SPION20 nanoparticles dispersed in 100 microliters of water and the measured temperature of 100 microliters of water without SPION20 nanoparticles, as a function of the ultrasound application time (in minutes).

[0636] Figure 3: (a) For a magnetic bob containing 800 μg of iron dispersed in 100 μL of water (magnetic bob) or 100 μL of water without the magnetic bob, the heating step of duration t1 is exposed to ultrasound at 3 MHz and power of 0.5, 1 and 1.5 W / cm², and the cooling step of duration t2 is not exposed to ultrasound, wherein the different values ​​of heating and cooling times (t1 and t2) during sequences 1 to 13 (SQ1 to SQ13) are given in Table 2. (b) The temperature difference between the temperature of the magnetic bob dispersed in the water (magnetic bob in (a)) and the temperature of the water without the magnetic bob (water in b) as a function of the duration (in minutes) of ultrasound application in different sequences.

[0637] Figure 4: Changes in specific absorption rate (SAP) as a function of iron concentration contained in BNF-starch nanoparticles (reference Micromod: 10-00102) in a suspension exposed to an alternating magnetic field with an average strength of 30 mTesla and a frequency of 196 kHz. BNF-Starch consists of ferromagnetic iron oxide nanoparticles with an average particle size of 18 nm.

[0638] Figure 5: (a) Histogram showing the percentage of viable U87-MG cells resulting from the following treatment: 2.5 10 5 U87-MG live cells were placed in magnetosomes at three concentrations (containing 0, 100, and 500 μg iron per mL of magnetosome culture medium and cells) and continuously exposed for 5 minutes to ultrasound at a power of 100 mW / cm² (middle column with lines along the rising and falling directions and filled with solid black circles), or at a power of 500 mW / cm² (right column with shaded lines along the falling direction and filled with black squares), or without ultrasound exposure (left column gray without shade). (b) For 2.5 10 5 U87-MG cells were placed in contact with iron at three different concentrations of magnetosomes: 0 mg / mL (filled with black circles with solid black lines), 100 μg / mL (white squares with dashed lines), and 500 μg / mL (black rhombuses with semi-solid lines), and exposed to ultrasound at a power of 100 mW / cm² for 5 minutes. Temperature changes were measured using an infrared camera as a function of the continuous ultrasound exposure time. (c) For 2.5 10 5U87-MG cells were placed in contact with iron at three different concentrations of magnetosomes: 0 mg / mL (filled with black circles with solid black lines), 100 μg / mL (white squares with dashed lines), and 500 μg / mL (black rhombuses with semi-solid lines), and exposed to ultrasound at a power of 500 mW / cm² for 5 minutes. Temperature changes were measured using an infrared camera as a function of the continuous ultrasound exposure time.

[0639] Figure 6: (a) Histogram showing the percentage of viable U87-MG cells after the following treatments: 2.5 10 5 U87-MG viable cells were contacted with three concentrations of magnetosomes (0, 100, and 500 μg of iron per milliliter of magnetosomes) and sequentially exposed to ultrasound. The sequence details are as follows: First ultrasound application for 1 minute (min), followed by no ultrasound application for 1 minute; second ultrasound application for 1 minute 24 seconds, followed by no ultrasound application for 1 minute 24 seconds; third ultrasound application for 1 minute, followed by no ultrasound application for 1 minute 30 seconds; fourth ultrasound application for 1 minute, followed by no ultrasound application for 1 minute 18 seconds; fifth ultrasound application for 1 minute 12 seconds, followed by no ultrasound application for 1 minute 18 seconds. During ultrasound application, the ultrasound power was set to 100 mW / cm² (middle column with lines along the rising and falling directions and filled with solid black circles) or 500 mW / cm² (right column with shaded lines and solid black squares). The percentage of viable cells resulting from treatments without ultrasound exposure is represented by the unshaded gray column on the left. (b) For 2.5 10 5 U87-MG cells were exposed to three different concentrations of magnetosomes: 0 mg / mL (dots with solid black lines), 100 μg / mL (white squares with dashed lines), and 500 μg / mL (black rhombuses with semi-solid lines), and then sequentially exposed to ultrasound at a power of 100 mW / cm² (sequence details are available in...). Figure 6 (a) is given in the legend), measuring temperature changes during treatment. (c) For 2.5 10 5 U87-MG cells were exposed to three concentrations of magnetosomes: 0 mg / mL (marked with black dots), 100 μg / mL (marked with dashed white dots), and 500 μg / mL (marked with semi-solid black rhombuses), and then sequentially exposed to ultrasound at a power of milliwatts per square centimeter (sequence details are available in...). Figure 6 (as shown in the legend of (a)) temperature changes were measured during treatment.

[0640] Figure 7(a) Percentage of viable cells after treatment with U87-MG cells either in contact with a magnetosome containing 1 mg / mL iron, or without contact with a magnetosome (0 mg / mL) and without laser exposure, followed by sequential exposure to a laser with an average power of 3 W / cm², with details of the sequence given in Figure 7(c) (sequential L), or continuous exposure to a laser with an average power of 3 W / cm² for 6 minutes (continuous L). (b) Temperature of U87-MG cells as a function of time after contact with magnetosomes containing 0 mg / mL and 1 mg / mL iron, and after continuous exposure to a laser with an average power of 3 W / cm² for 6 minutes. (c) Temperature as a function of time in U87-MG cells exposed to magnetosomes at 0 mg / mL and 1 mg / mL, and subsequently to a laser with an average power of 3 W / cm², the details of which are as follows: First sequence i) applying an average power of 3 W / cm² for 60 seconds until the temperature reaches 45°C, ii) with no laser applied for 18 seconds, causing the temperature to decrease from 45°C to 37°C; Second sequence: i) applying an average power of 3 W / cm² for 17.5 seconds, causing the temperature to rise from 37°C to 45°C, ii) with no laser applied for 24 seconds, causing the temperature to decrease from 45°C to 37°C. The sequence is as follows: First sequence: i) Applying a laser with an average power of 3 watts per square centimeter over 17.5 seconds, causing the temperature to rise from 37 degrees Celsius to 45 degrees Celsius; ii) Not applying the laser over 20 seconds, causing the temperature to drop from 45 degrees Celsius to 37 degrees Celsius. Second sequence: i) Applying an average power of 3 watts per square centimeter over 15 seconds, causing the temperature to rise from 37 degrees Celsius to 45 degrees Celsius; ii) Not applying the laser over 20.5 seconds, causing the temperature to drop from 45 degrees Celsius to 37 degrees Celsius. Third sequence: i) Applying an average power of 3 watts per square centimeter over 14.5 seconds, causing the temperature to rise from 37 degrees Celsius to 45 degrees Celsius. Fourth sequence: i) Applying an average power of 3 watts per square centimeter over 15 seconds, causing the temperature to rise from 37 degrees Celsius to 45 degrees Celsius; ii) Not applying the laser over 21.5 seconds, causing the temperature to drop from 45 degrees Celsius to 37 degrees Celsius. Fifth sequence: i) Applying an average power of 3 watts per square centimeter over 14.5 seconds, causing the temperature to drop from 37 degrees Celsius to 45 degrees Celsius. The seventh sequence: i) applying an average power of 3 watts per square centimeter for 15 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 21.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the eighth sequence: i) at 13...The ninth sequence: i) applying an average power of 3 watts per square centimeter over 5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 22 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the tenth sequence: i) applying an average power of 3 watts per square centimeter over 13 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 21 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the eleventh sequence: i) applying an average power of 3 watts per square centimeter over 15 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 23 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; The temperature decreased to 37 degrees Celsius; the twelfth sequence: i) applying an average power of 3 watts per square centimeter over 15 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 25 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the thirteenth sequence: i) applying an average power of 3 watts per square centimeter over 14.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 24.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the fourteenth sequence: i) applying an average power of 3 watts per square centimeter over 14.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 24.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the fifteenth sequence: i) applying an average power of 3 watts per square centimeter over 12.5 seconds to raise the temperature from 37 degrees Celsius to 37 degrees Celsius. The sixteenth sequence: i) applying an average power of 3 watts per square centimeter for 15 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying laser for 22.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the seventeenth sequence: i) applying an average power of 3 watts per square centimeter for 12.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying laser for 22.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the eighteenth sequence: i) applying an average power of 3 watts per square centimeter for 13.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying laser for 24 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius. Celsius; Nineteenth sequence: i) applying an average power of 3 watts per square centimeter over 13.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) at 21.The twentieth sequence: i) applying an average power of 3 watts per square centimeter over 14 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 21 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius. The twenty-first sequence: i) applying an average power of 3 watts per square centimeter over 14.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 23 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius. The twenty-second sequence: i) applying an average power of 3 watts per square centimeter over 14 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 16 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius. The total duration of the laser application was 6 minutes and 2 seconds.

[0641] Figure 8(a) Percentage of viable cells after treatment with 3T3 cells either in contact with a magnetosome of 1 mg / mL iron, or without contact with a magnetosome (0 mg / mL) and without laser exposure, followed by sequential exposure to a laser with an average power of 3 W / cm², with details of the sequence given in Figure 8(c) (sequential L), or continuous exposure to a laser with an average power of 3 W / cm² for 6 minutes (continuous L). (b) Temperature of 3T3 cells in contact with magnetosomes of 0 mg / mL and 1 mg / mL, and continuous exposure to a laser with an average power of 3 W / cm² for 6 minutes as a function of time. c) Temperature of 3T3 cells exposed to magnetosomes at 0 mg / mL and 1 mg / mL as a function of time, and the sequence details are as follows: First sequence i) applying an average power of 3 W / cm² for 90 seconds until the temperature reaches 45°C, ii) with no laser applied for 21 seconds, allowing the temperature to decrease from 45°C to 37°C; Second sequence: i) applying an average power of 3 W / cm² for 17.5 seconds, allowing the temperature to rise from 37°C to 45°C, ii) with no laser applied for 22 seconds, allowing the temperature to decrease from 45°C to 37°C. The sequence is as follows: First sequence: i) Applying a laser with an average power of 3 watts per square centimeter for 17.5 seconds, causing the temperature to rise from 37 degrees Celsius to 45 degrees Celsius; ii) Not applying the laser for 20.5 seconds, causing the temperature to drop from 45 degrees Celsius to 37 degrees Celsius. Second sequence: i) Applying an average power of 3 watts per square centimeter for 14.5 seconds, causing the temperature to rise from 37 degrees Celsius to 45 degrees Celsius; ii) Not applying the laser for 20.5 seconds, causing the temperature to drop from 45 degrees Celsius to 37 degrees Celsius. Third sequence: i) Applying an average power of 3 watts per square centimeter for 15.5 seconds, causing the temperature to rise from 37 degrees Celsius to 45 degrees Celsius; ii) Not applying the laser for 19 seconds, causing the temperature to drop from 45 degrees Celsius to 37 degrees Celsius. Sixth sequence: i) Applying an average power of 3 watts per square centimeter for 15.5 seconds, causing the temperature to drop from 37 degrees Celsius to 45 degrees Celsius. The seventh sequence: i) applying an average power of 3 watts per square centimeter for 18.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 19.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the eighth sequence: i) applying an average power of 3 watts per square centimeter for 18.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 20 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius;The ninth sequence: i) applying an average power of 3 watts per square centimeter over 5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 21 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the tenth sequence: i) applying an average power of 3 watts per square centimeter over 18.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 19.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the eleventh sequence: i) applying an average power of 3 watts per square centimeter over 17.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius; ii) not applying the laser for 18.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius. The temperature decreased to 37 degrees Celsius; the twelfth sequence: i) applying an average power of 3 watts per square centimeter over 18 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 19.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the thirteenth sequence: i) applying an average power of 3 watts per square centimeter over 17.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 18.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the fourteenth sequence: i) applying an average power of 3 watts per square centimeter over 17.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 18.5 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the fifteenth sequence: i) applying an average power of 3 watts per square centimeter over 19.5 seconds to raise the temperature from 37 degrees Celsius to 37 degrees Celsius. The sixteenth sequence: i) applying an average power of 3 watts per square centimeter for 18 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 19 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the seventeenth sequence: i) applying an average power of 3 watts per square centimeter for 17.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 20 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius; the eighteenth sequence: i) applying an average power of 3 watts per square centimeter for 17.5 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) not applying the laser for 20 seconds to lower the temperature from 45 degrees Celsius to 37 degrees Celsius. Celsius; Nineteenth sequence: i) applying an average power of 3 watts per square centimeter over 19 seconds to raise the temperature from 37 degrees Celsius to 45 degrees Celsius, ii) at 18.If the laser is not applied for 5 seconds, the temperature drops from 45 degrees Celsius to 37 degrees Celsius.

[0642] Figure 9: (a) ROS production rate after the following treatments: 3T3 cells were either in contact with a magnetosome containing 1 mg / mL iron (M-CMD) or not in contact with the magnetosome (0 mg / mL) and not exposed to a laser, or were continuously exposed to a laser with an average power of 3 W / cm² over 6 minutes, or were sequentially exposed to a laser with an average power of 3 W / cm², wherein details of the sequence are given in Figure 7(c). (b) ROS production rate after the following treatments: 3T3 cells were either in contact with a magnetosome containing 1 mg / mL iron or not in contact with the magnetosome (0 mg / mL) and not exposed to a laser, or were continuously exposed to a laser with an average power of 3 W / cm² over 6 minutes, or were sequentially exposed to a laser with an average power of 3 W / cm², wherein details of the sequence are given in Figure 8(c).

[0643] Figure 10: (a) ROS production rate after the following treatments: 3T3 cells were either in contact with a magnetosome containing 1 mg / mL iron (M-CMD) or not in contact with the magnetosome (0 mg / mL) and or not exposed to the alternating magnetic field, or were continuously exposed to an alternating magnetic field of 34–47 mTesla and 198 kHz for 30 minutes, or were sequentially exposed to an alternating magnetic field of 34–47 mTesla and 198 kHz, wherein the sequence details are as follows: First sequence: i) applying an alternating magnetic field of 34–47 mTesla and 198 kHz for 5 minutes until the temperature reaches 45°C, ii) not applying the alternating magnetic field for 2.2 minutes, resulting in the temperature decreasing from 45°C to 37°C; Second sequence: i) applying 34–47 mTesla and 198 kHz for 3.7 minutes. The sequence is as follows: 1) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 3.1 minutes until the temperature reaches 45 degrees Celsius; 2) Disappearing the alternating magnetic field for 2.7 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; 3) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 2.1 minutes until the temperature reaches 45 degrees Celsius; 4) Disappearing the alternating magnetic field for 2.3 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; 5) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 1.8 minutes until the temperature reaches 45 degrees Celsius; 6) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 1.8 minutes. The sequence is as follows: 1) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 2.2 minutes until the temperature reaches 45 degrees Celsius; 2) Not applying the alternating magnetic field for 1.5 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; 3) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 2.4 minutes until the temperature reaches 45 degrees Celsius; 4) Not applying the alternating magnetic field for 2.9 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; 5) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 2.8 minutes until the temperature reaches 45 degrees Celsius; 6) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 2.8 minutes until the temperature reaches 45 degrees Celsius; 7) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 2.8 minutes until the temperature reaches 45 degrees Celsius; 8) Applying an alternating magnetic field of 34-47 millisaels at a frequency of 198 kHz for 2.8 minutes until the temperature reaches 45 degrees Celsius. The alternating magnetic field of kilohertz continues until the temperature reaches 45 degrees Celsius, ii) in 2.The alternating magnetic field was not applied for 7 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; Ninth sequence: i) applying an alternating magnetic field of 34-47 millitalas at a frequency of 198 kHz for 2.4 minutes until the temperature reached 45 degrees Celsius, ii) not applying the alternating magnetic field for 2.4 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; Tenth sequence: i) applying an alternating magnetic field of 34-47 millitalas at a frequency of 198 kHz for 2.1 minutes until the temperature reached 45 degrees Celsius, ii) not applying the alternating magnetic field for 2.7 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; (b) ROS production rate after the following treatment: U87-MG1 cells were in contact with or not in contact with magnetosomes (M-CMD) at a concentration of 0 mg / mL (0 mg / mL). (mg / mL) and either not exposed to the alternating magnetic field, or continuously exposed to an alternating magnetic field of 34-47 mtesas and 198 kHz for 30 minutes, or sequentially exposed to an alternating magnetic field of 34-47 mtesas and 198 kHz, wherein the details of the sequence are as follows: First sequence: i) applying an alternating magnetic field of 34-47 mtesas and 198 kHz for 5 minutes until the temperature reaches 45 degrees Celsius, ii) not applying the alternating magnetic field for 2.2 minutes, resulting in a decrease in temperature from 45 degrees Celsius to 37 degrees Celsius; Second sequence: i) applying an alternating magnetic field of 34-47 mtesas and 198 kHz for 3.7 minutes until the temperature reaches 45 degrees Celsius, ii) not applying the alternating magnetic field for 2.7 minutes, resulting in a decrease in temperature from 45 degrees Celsius to 37 degrees Celsius; Third sequence: i) in 3.1 The fourth sequence: i) applying an alternating magnetic field of 34-47 millitalas at a frequency of 198 kHz for 2.3 minutes until the temperature reaches 45 degrees Celsius; ii) not applying the alternating magnetic field for 2.3 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; The fifth sequence: i) applying an alternating magnetic field of 34-47 millitalas at a frequency of 198 kHz for 1.8 minutes until the temperature reaches 45 degrees Celsius; ii) not applying the alternating magnetic field for 1.5 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; The sixth sequence: i) applying an alternating magnetic field of 34-47 millitalas at a frequency of 198 kHz for 2.8 minutes until the temperature reaches 45 degrees Celsius; ii) not applying the alternating magnetic field for 1.5 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius;The seventh sequence: i) applying an alternating magnetic field with an intensity of 34-47 millitas and a frequency of 198 kHz for 2 minutes until the temperature reaches 45 degrees Celsius; ii) not applying the alternating magnetic field for 2.6 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; the eighth sequence: i) applying an alternating magnetic field with an intensity of 34-47 millitas and a frequency of 198 kHz for 2.4 minutes until the temperature reaches 45 degrees Celsius; ii) not applying the alternating magnetic field for 2.9 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; the ninth sequence: i) applying an alternating magnetic field with an intensity of 34-47 millitas and a frequency of 198 kHz for 2 minutes until the temperature reaches 45 degrees Celsius; ii) not applying the alternating magnetic field for 2.7 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius; The tenth sequence: i) applying an alternating magnetic field of 34-47 millitalas at a frequency of 198 kHz for 2.1 minutes until the temperature reaches 45 degrees Celsius; ii) not applying the alternating magnetic field for 2.4 minutes, causing the temperature to decrease from 45 degrees Celsius to 37 degrees Celsius;

[0644] Figure 11: (a) Percentage of viable cells after the following treatments: 3T3 cells were in contact with magnetosomes containing 1000, 500, 250, and 16 μg / mL iron or not in contact with magnetosomes (0 mg / mL) and or not exposed to gamma rays (control), or exposed to different doses of gamma rays: 5, 10, 20, 40, and 80 Gy. (b) Rate of ROS production after the following treatments: 3T3 cells were in contact with magnetosomes containing 1000, 500, 250, and 16 μg / mL iron or not in contact with magnetosomes (0 mg / mL) and or not exposed to gamma rays, or exposed to different doses of gamma rays: 5, 10, 20, 40, and 80 Gy.

[0645] Figure 12: (a) Percentage of viable cells after the following treatments: CAL-33 cells were in contact with magnetosomes containing 1000, 500, 250, and 16 μg / mL iron or not in contact with magnetosomes (0 mg / mL) and or not exposed to gamma rays (control), or exposed to different doses of gamma rays: 5, 10, 20, 40, and 80 Gy. (b) Rate of ROS production after the following treatments: CAL-33 cells were in contact with magnetosomes containing 1000, 500, 250, and 16 μg / mL iron or not in contact with magnetosomes (0 mg / mL) and or not exposed to gamma rays, or exposed to different doses of gamma rays: 5, 10, 20, 40, and 80 Gy. Detailed Implementation

[0646] Example 1:

[0647] Materials and methods:

[0648] Nanoparticles: We used magnetosomes extracted from magnetotactic bacteria and further purified them to remove most of the organic matter from the magnetotactic bacteria, including: i) a core or mineral of magnetohypermeate, comprising 0.3 percent by mass from the magnetotactic bacteria, and ii) a coating surrounding the core made of carboxymethyl dextran. The magnetosomes were formed into chains and prepared using an adapted and improved scheme described in patent PCT / FR2016 / 000095 (publication number WO2016 / 203121A1), incorporated in reference (Embodiment 8). These magnetosomes are represented by M-CMD. We also used i) 35 ± 13 nm iron oxide nanoparticles purchased from Sigma, designated as Sigma Nanoparticles (reference number: 637106-25G, lot number #MKBK2270v), ii) 20 nm superparamagnetic iron oxide nanoparticles purchased from Micromod, designated as SPION20 (nanomag®-D-spio20, reference number: 79-02-201), iii) 50 nm superparamagnetic iron oxide nanoparticles purchased from Micromod, designated as SPION50 (synomag-D50, Ref: 104-000-501), and iv) 100 nm superparamagnetic iron oxide nanoparticles purchased from Micromod, designated as SPION100 (nanomag®-D-spio 100, reference number: 79-00-102).

[0649] Preparation of samples containing nanoparticles inserted into tissues or dispersed in waterTo conduct heating experiments in tissue, 10 μL of a water-only suspension or nanoparticles containing 204 μg of iron (magnetoids and sigma or sigma nanoparticles) were uniformly mixed into 4.5 cm³ of liver tissue to obtain a concentration of 45 μg of iron per cm³ of liver tissue. To conduct heating experiments under aqueous conditions, 100 μL of water alone or 100 μL of water mixed with nanoparticles containing 100 μg of iron (magnetoids, sigma, SPION20, SPION50, SPION100) was mixed in a 200 μL Eppendorf tube.

[0650] The heating device generates ultrasonic waves: Samples of tissue with / without nanoparticles or water with / without nanoparticles were exposed to ultrasound at an intensity of 0.5, 1, or 1.5 W / cm³ at a frequency of 3 MHz. The intensity corresponds to red on the device, and there may be differences between the ultrasound intensity indicated on the body part and that indicated by the choroid 190i. For ultrasound application, we used a Physical Action 190i ultrasound generator with a transducer surface area of ​​4 cm². The ultrasound power indicated in the examples corresponds to the ultrasound power read on the 190i ultrasound generator, not the ultrasound power measured using an external probe. We used an ultrasound gel (Winelec, reference number: 1741 / WINELEC) positioned between the transducer and the sample to facilitate ultrasound transmission.

[0651] Temperature measurement We used an infrared camera (EasIRTM-2, Optophase) positioned 13 cm above the transducer to measure the spatial distribution of temperature as a function of time during the experiment. We measured the temperature distribution at the following time points: 0 sec, 30 sec, 1 min, 2 min, 3 min, 4 min, 5 min, 6 min, 7 min, 9 min, and 10 min. We only considered the maximum temperature at each time point.

[0652] Results and discussion:

[0653] Non-sequential heating experiments in tissues:

[0654] Figure 1 shows the temperature difference between tissue with and without nanoparticles measured at each time point, with an ultrasonic power of 0.5 watts per square centimeter (Figure 1(a), 1 watt per square centimeter (Figure 1(a)). Figure 1(b) 1.5 W / cm² (Fig. 1(c)). At the three different test powers, ΔT is positive, indicating that the temperature increase is more important for tissues containing nanoparticles than for tissues without nanoparticles. At the lowest power of 0.5 W / cm², sigma nanoparticles generate more heat than magnetosomes, while at 1.5 W / cm², the opposite behavior is observed, with magnetosomes generating more heat than sigma nanoparticles.

[0655] For magnetosomes mixed in tissue and exposed to different ultrasound powers of 0.5, 1, or 1.5 watts per square centimeter, we also estimated ΔT 10minreal(M) The value of is equal to ΔT. 10min(M) - ΔT 10min(W) , where ΔT 10min(M) and ΔT 10min(W The temperatures of tissue samples containing and without magnetosomes were observed 10 minutes after ultrasound application. We observed ΔT 10minreal(M) The temperature increased from 6 degrees Celsius at 0.5 watts per square centimeter to 28 degrees Celsius at 1.5 watts per square centimeter (Table 1). We also estimated the percentage increase in temperature, i.e., the temperature rise. （M） The temperature rises using the formula （M） =ΔT 10min(M) / ΔT 10min(W) -1). 100 indicates that it increases from 37% at 0.5 watts per square centimeter to 100% at 1.5 watts per square centimeter (Table 1). We also use the formula SAR. real(M) =Slope real(M) .C v / C nano The specific absorption rate of the magnetosomes inserted into the tissue was estimated, where the slope real(M) =Slope (M) – Slope (W) slope (M) and slope (W) Representative from Figure 1 (a) The initial slope of the temperature over time derived from 1(c), C v = 4.2 joules per Kelvin per gram is the specific heat of water. Cnano is the concentration of nanoparticles expressed as grams of nanoparticles per milliliter of water. SAR real(M) The iron content increased from 5-12 watts per gram at 0.5-1 watts per square centimeter to 71 watts per gram at 1.5 watts per square centimeter (Table 1). We also estimated the percentage increase in slope, i.e., the slope increase. （M） The slope increases using the formula. This indicates that it increased from 9-47% at 0.5-1 watts per square centimeter to 124% at 1.5 watts per square centimeter.

[0656] For Sigma nanoparticles mixed in tissue and exposed to different ultrasonic powers of 0.5, 1, or 1.5 W / cm², we also estimated ΔT 10minreal(S) The value of is equal to ΔT. 10min(S) -ΔT 10min(W) , where ΔΔT 10min(S) and ΔT 10min(W) The temperature increases were observed in tissues containing and without sigma nanoparticles after 10 minutes of ultrasound application. We observed ΔT 10minreal(S) The temperature decreased from 14 degrees Celsius at 0.5 watts per square centimeter to 6-7 degrees Celsius at 1-1.5 watts per square centimeter (Table 1). We also estimated the percentage increase in temperature, i.e., the temperature rise. （S） The temperature rises using the formula （S） = (ΔT 10min(S) / ΔT 10min(W) -1).100 indicates that it decreased from 90% at 0.5 W / cm² to 17-26% at 1-1.5 W / cm² (Table 1). We also estimated the specific absorption of Sigma nanoparticles inserted into tissue. real(S) The value is expressed in watts per gram of iron in sigma nanoparticles (W / g) Fe Using the formula: specific absorption rate real(S) = Slope real(S) .C v / C nano The slope real(S) This indicates that from the perspective of Sigma nanoparticles Figure 1 The initial slope of the temperature change over time, derived from graphs (a) to (c), is C. v = 4.2 J / KL / gram is the specific heat of water. Cnano is the concentration of magnetosomes expressed as grams of magnetosomes per milliliter of water. Specific Absorption Rate real（S） The wattage was maintained at 16–28 W / gFe between 0.5–1.5 W / cm² (Table 1). We also estimated the percentage increase in slope, i.e., the slope increase. (S) The slope increases using the formula. (S) = (slope) (S) / slope (W) -1) .100 indicates that it decreases from 118% at 0.5 watts per square centimeter to 30-36% at 1-1.5 watts per square centimeter.

[0657] Non-sequential heating experiment in water:

[0658] Figure 2(a), 2(b), 2(c), 2(d), and 2(e) show ΔT, where ΔT is the difference between the temperature of a suspension containing different nanoparticles dispersed in water and the temperature of water without nanoparticles when different suspensions are exposed to ultrasound at 0.5, 1, or 1.5 watts per square centimeter for 10 minutes. Figure 2 (a), 2(b), 2(c), 2(d), and 2(e) show ΔT as a function of time for the magnetic nanoparticles, sigma, SPION50, SPION100, and SPION20, respectively. For the different nanoparticles and three different test powers, ΔT is positive, indicating that the temperature increase is more significant for nanoparticles dispersed in water than for water alone.

[0659] For magnetosomes mixed in tissue and exposed to different ultrasound powers of 0.5, 1, or 1.5 watts per square centimeter, we also estimated ΔT 10minreal(M) The value of is equal to ΔT. 10min(M) - ΔT 10min(W) , where ΔT 10min(M) and ΔT 10min(W The temperatures of tissue samples containing and without magnetosomes were observed 10 minutes after ultrasound application. We observed ΔT 10minreal(M) Maintaining temperatures between 3 and 9 degrees Celsius at 0.5 watts per square centimeter and 1.5 watts per square centimeter (Table 2) resulted in a ΔT observed in tissues compared to 1.5 watts per square centimeter. 10minreal(M) The values ​​are smaller (Table 1). We also estimated the percentage increase in temperature, i.e., the temperature increase... （M） The temperature rises using the formula （M） = (ΔT) 10min(M) / ΔT 10min(W) -1).100 indicates that it decreased from 37-43% at 0.5-1 watts per square centimeter to 10% at 1.5 watts per square centimeter (Table 2), and was also less than the temperature rise measured in tissue at 1.5 watts per square centimeter. （M） (Table 1). We also use the formula SAR. real(M) =Slope real(M) .C v / C nano The specific absorption rate of the magnetosomes inserted into the tissue was estimated, where the slope real(M) =Slope (M) – Slope (W) slope (M) and slope (W) Representative from Figure 2 (a) The derived initial slope of temperature over time, C v= 4.2 joules per Kelvin per gram is the specific heat of water. Cnano is the concentration of nanoparticles expressed as grams of nanoparticles per milliliter of water. SAR real(M) The slope increased from 294 W / gFe at 0.5 W / cm² to 424 W / gFe at 1.5 W / cm² (Table 2), higher than the values ​​measured in the tissue (Table 1). We also estimated the percentage increase in slope, i.e., the slope increase. (M) The slope increases using the formula. (M) = (slope) (M) / slope (W) -1) .100 indicates that it remains at 16-24% at 0.5-1.5 watts per square centimeter (Table 2), less than the 124% inferred in the tissue at 1.5 watts per square centimeter (Table 1).

[0660] For Sigma nanoparticles mixed in tissue and exposed to different ultrasonic powers of 0.5, 1, or 1.5 W / cm², we also estimated ΔT 10minreal(S) The value of is equal to ΔT. 10min(S) -ΔT 10min(W) , where ΔΔT 10min(S) and ΔT 10min(W) The temperature increases were observed in tissue samples containing and without sigma nanoparticles after 10 minutes of ultrasound application. We observed that at ultrasound energy of 0.5–1.5 watts per square centimeter, ΔT… 10minreal(S) Maintain at 6-12 degrees Celsius (Table 2). We also estimated the percentage increase in temperature, i.e., the temperature rise. （S） The temperature rises using the formula （S） = (ΔT 10min(S) / ΔT 10min(W) -1).100 indicates. For power of 0.5–1.5 watts per square centimeter, it remains at 31–60% (Table 2). We also estimated the specific absorption rate (SAR) of Sigma nanoparticles inserted into the tissue. real(S) The value is expressed in watts per gram of iron in sigma nanoparticles (W / g) Fe Using the formula: SAR real(S) = Slope real(S) .C v / C nano The slope real(S) This indicates that from the perspective of Sigma nanoparticles Figure 1 The initial slope of the temperature change over time, derived from graphs (a) to (c), is C. v = 4.2 JK -1 g -1Cnano is the specific heat of water, expressed as the concentration of nanoparticles in grams of iron per milliliter of water in sigma nanoparticles. SAR real（S） The slope increased from 0 W / gFe at 0.5 W / cm² to 2686 W / gFe at 1.5 W / cm² (Table 2). We also estimated the percentage increase in slope, i.e., the slope increase. （s） The slope increases using the formula. （s） =(slope) (S) / Slope (W) -1).100 indicates that it increases from 0.8% at 0.5-1 watts per square centimeter to 99% at 1.5 watts per square centimeter.

[0661] For SPION50, SPION100, and SPION20 nanoparticles mixed in tissue and exposed to different ultrasonic powers of 0.5, 1, or 1.5 W / cm², we also estimated ΔT 10minreal(S50) ΔT 10minreal(S100) , and ΔT 10minreal(S20) The values ​​of and are respectively equal to ΔT 10min(S50) -ΔT 10min(W) ΔT 10min(S100) -ΔT 10min(W) and ΔT 10min(S20) - ΔT 10min(W) , ΔT 10min(S50) ΔT 10min(S100) ΔT 10min(S20)和 ΔT 10min(W) The temperature increases were observed in tissues containing SPION50, SPION100, and SPION20 nanoparticles and in tissues without SPION20 nanoparticles, respectively, after 10 minutes of ultrasound application. We observed that for ultrasound energies of 0.5–1.5 W / cm², ΔT… 10min(S50) ΔT 10min(S100) and ΔT 10min(S20) Maintain at 0-7°C (Table 2). We also estimated the percentage increase in temperature, i.e., the temperature rise. （S） The temperature rises using the formula (S100) = (ΔT 10min(S100) / ΔT 10min(W) -1).100 For SPION100, temperature rise (S20) = (ΔT 10min(S20) / ΔT 10min(W) -1). 100 for SPION. For power of 0.5–1.5 W / cm², it remains 1–35% for different SPIONs (Table 2). We also estimated the specific absorption SAR of SPION50, SPION100, and SPION20 nanoparticles inserted into tissue.real(S50) SAR real(S100) SAR real(S20) The values ​​are expressed in watts per gram of iron in SPION50, SPION100, and SPION20 nanoparticles (W / g). Fe Therefore, we use the formula: SAR real(S50) = Slope real(S50) .C v / C nano SAR real(S100) = Slope real(S100) .C v / C nano SAR real(S20) = Slope real(S20) .C v / C nano For SPION50, SPION100, and SPION20 respectively, the slopes are... real(S50) slope real(S100)， slope real(S20) This indicates that, from Figure 2(c) for SPION50, SPION100... Figure 2 (d), and the change of the initial slope of the temperature change over time derived from Figure 2(e) for SPION20, C v = 4.2 joules per Kelvin per gram is the specific heat of water. Cnano is the concentration of nanoparticles in grams of iron per milliliter of water in SPION50, SPION20, and SPION100 nanoparticles. SAR real(S50) , and SAR real(S100) From 0.5-1 watt per square centimeter, the efficiency is 0-677 W / g. Fe 787-2795 W / g when increased to 1.5 watts per square centimeter Fe (Table 2). We also estimated the percentage increase in slope. (S20) The slope increases (S50) The slope increases (S100)， The slope increases using the formula. (S20) =(slope) (S20) / slope (W) -1).100 For SPION20, the slope increases. (S50) =(slope) (S50) / slope (W) -1).100 for SPION50 and slope increase (S100) =(slope) (S100) / slope (W) -1).100 is indicated for SPION100. It maintains a power output of 0-104% between 0.5 and 1.5 watts per square centimeter.

[0662] Experiment on sequential heating of water:

[0663] Eppendorf tubes containing 500 micrograms of magnetic particles dispersed in 100 microliters of water were sequentially exposed to sound waves. Figure 3 (a) shows 13 sequences (SQ1 to SQ13), each consisting of ultrasound applied at a power of 1.5 watts per square centimeter and a frequency of 3 MHz during time t1, followed by no ultrasound applied during time t2. Time t1 corresponds to the time required to reach the target temperature of 43.5 ± 1.5 degrees Celsius during the heating step, while time t2 corresponds to th...

Claims

1. A composition comprising metallic ferrimagnetic nanoparticles with a size of less than 100 nm dispersed in a dispersing excipient, for use in acoustic hyperthermic medical therapy of an individual body part, characterized in that: 1) The specific absorption rate of the composition is less than 1000 watts / gram of nanoparticles or 1000 watts / gram of metal contained in the nanoparticles. 2) The concentration of nanoparticles in the composition (C) n Less than 100 mg nanoparticles / 1 mL composition or 100 mg nanoparticles / 1 cm 3 The body parts mentioned in the medical treatment, and 3) After applying sound waves to the nanoparticles, the composition is able to increase the temperature of the nanoparticles or the body part by a value ΔT, wherein the value ΔT is less than 5°C / second of sound wave application, and the value ΔT is obtained by using the concentration C n However, maintaining a speed below 5°C / second The concentration C n The specific absorption rate is suitable for preventing the composition from being heated by the applied acoustic waves, and thus preventing it from exceeding the ΔT.

2. The composition according to claim 1, wherein the application time of the sound wave is 10... -3 seconds and 10 20 Between minutes.

3. The composition for the application according to claim 1 or 2, wherein the specific absorption rate is less than 100 watts / gram nanoparticles or 100 watts / gram of metal contained in the nanoparticles.

4. The composition for any one of claims 1 to 3, wherein the specific absorptivity is measured by applying an acoustic wave to the nanoparticles and is defined as SAR. AW = α(ΔT / δt) N or SAR real = α real [(ΔT / δt) real ],in: α and α real It is the proportionality coefficient. (ΔT / δt) real = (ΔT / δt) N - (ΔT / δt) WN , (ΔT / δt)N is the initial change in temperature of the body part over time in the presence of the nanoparticles, and (ΔT / δt)WN is the initial change in temperature of the body part over time in the absence of the nanoparticles, and The specific absorption rate is measured by applying an acoustic wave to the nanoparticles using at least one of the following conditions: (1) Ultrasonic intensity higher than 0.2 W / cm 2 , (2) Ultrasonic intensity is less than 1000 W / cm² 2 , (3) The ultrasonic frequency is greater than 100 kHz. (4) The ultrasonic frequency is below 100 MHz. (5) Nanoparticle concentration is higher than 0.1 µg / cm³ 3 Body parts, or (6) Nanoparticle concentration is less than 1 g / cm³ 3 Body parts.

5. The composition for any one of claims 1 to 4, wherein the value of the specific absorptivity measured under applied acoustic waves is different from that measured by applying an alternating magnetic field (SAR) to the nanoparticles. AMF The measured value is the specific absorption rate.

6. The composition according to any one of claims 1 to 5, wherein the dispersing excipient is adapted to maintain the nanoparticles dispersed or arranged in chains in the composition, or adapted to maintain the concentration of the nanoparticles below C0. T Value, wherein C T The value is higher than the concentration of nanoparticles in the composition when the applied sound wave increases the temperature of the composition by more than 5°C / second.

7. The composition of any one of claims 1 to 6, wherein the sound waves are applied sequentially to the body part or nanoparticles, wherein the sequential application of the sound waves to the body part corresponds to the application of sound waves associated with at least one heating step and at least one cooling step.

8. The composition for application according to any one of claims 1 to 7, wherein ΔT is further defined as follows: (a) An increase in temperature of the body part or nanoparticles exposed to sound waves; or (b) An increase in temperature above physiological temperature, or above the temperature of the body part or nanoparticles reached before the application of the sound waves; or (c) The temperature or temperature increase (T) of the body part containing the nanoparticles exposed to sound waves. NPBP ) and selected from (T) BP The difference between the temperatures of ) and T, wherein T BP Limited to the following: (i) The temperature of the body portion not containing the nanoparticles or an increase in temperature, the body portion being exposed to sound waves, or (ii) The temperature of the body portion containing the nanoparticles increases, and the body portion is exposed to sound waves; or (d) The difference between the temperature measured or occurring when sound waves are applied sequentially to the nanoparticles and the temperature measured or occurring when sound waves are applied continuously to the nanoparticles.

9. The composition for application according to claim 5, wherein (SAR) AW -SAR AMF ) / SAR AW Greater than 1%.

10. The composition for any one of claims 1 to 9, wherein an acoustic wave is applied to the nanoparticles until a saturation temperature is reached, wherein the saturation temperature is a desired temperature below 100°C during the heating step.

11. The composition for application according to any one of claims 1 to 10, wherein the high-temperature treatment is characterized by at least one of the following properties: i) The temperature during heating should be kept below 100°C during treatment; ii) The temperature during heating is maintained below the highest temperature reached during high-intensity ultrasound treatment, and iii) The treatment is not thermal ablation or is different from thermal ablation.

12. The composition for any one of claims 1 to 11, wherein the sound waves are applied to a volume V1 of the composition, or the body part or nanoparticles are contained in a volume V2, and V2 is smaller than V1.

13. The composition of claim 7, wherein the sequential application of the sound waves on the body part comprises at least one sequence of: (a) Applying a sound wave during time t1, and then not applying a sound wave during time t2, or (b) Apply a sound wave during time t1 and then apply another sound wave during time t3, wherein the intensity, power, energy or frequency of the sound wave applied during time t3 is lower than the intensity, power, energy or frequency of the sound wave applied during time t1.

14. The composition for application according to claim 13, wherein t1, t2 and / or t3 are in the range of 10 -3 seconds and 10 20 Between minutes.

15. The composition of claim 13, wherein the sequence is repeated at least twice.

16. The composition of claim 13, comprising at least one treatment course, wherein the treatment course consists of a plurality of sequences separated by time intervals longer than t1, t2, t3, t1+t2 or t1+t3, preferably by a factor greater than 1.

001.

17. The composition for any application according to any one of claims 1 to 16, wherein the sound wave has at least one of the following properties: i) Power or power density less than 1000 W (watts). ii) Power or power density less than 1000 W / cm³, W / cm³ 2 or W / cm 3 , iii) Body parts with power or power density below 1000 W / cm², W / cm² 2 Body parts or W / cm 3 body parts, iv) Transducers with power or power density below 1000 W / cm², W / cm² 2 transducer or W / cm 3 The transducer, v) Nanoparticles with power or power density below 1000 W / g. vi) Energy or energy density less than 10 5 W× seconds, vii) Energy or energy density below 10 5 W× seconds / cm, W× seconds / cm 2 Or W × seconds / cm 3 , viii) Energy or energy density below 10 5 W× seconds / cm for body parts, W× seconds / cm 2 Body parts or W× seconds / cm 3 body parts, ix) Energy or energy density less than 10 5 Transducer with W×s / cm, W×s / cm 2 Transducer, W×s / cm 3 The transducer, x) Energy or energy density below 10 5 J (joule) xi) Energy or energy density below 10 5 J / cm, J / cm 2 or J / cm 3 , xii) Energy or energy density below 10 5 J / cm body parts, J / cm 2 Body parts or J / cm 3 body parts, xiii) Energy or energy density below 10 5 Transducer with J / cm, J / cm 2 of xiv) Transducer, J / cm 3 The transducer, xv) Energy or energy density below 10 5 J / g nanoparticles, xvi) frequency below 10 5 MHz, xvii) Penetration depth in the body part greater than 10 -5 cm.

18. The composition for any one of the applications of claims 1 to 17, wherein the sound wave is ultrasound.

19. The composition for any one of the applications of claims 1 to 18, wherein the nanoparticles are acoustic agents.

20. The composition for the application according to claim 18 or 19, wherein the application is sonodynamic therapy.

21. The composition for application according to claim 20, wherein the sonodynamic therapy is wherein the temperature increase is less than 10°C. 3 Therapies at ℃, 500℃, 100℃, 50℃, 25℃, 10℃, 5℃, 2℃ or 1℃.

22. The composition for any one of claims 1 to 21, wherein the nanoparticles are synthesized by magnetotactic bacteria, derived from magnetotactic bacteria, extracted from magnetotactic bacteria, or isolated from magnetotactic bacteria.

23. The composition for any one of the applications of claims 1 to 21, wherein the nanoparticles are chemical analogs of magnetosomes.

24. The composition of any one of claims 1 to 23, wherein the medical treatment is a treatment for a disease or condition selected from: a disease related to cell proliferation that differs from cell proliferation in a healthy individual, a disease related to the presence of pathological cells in a body part, a disease related to the presence of a pathological site in an individual or body part, a disease or disorder or dysfunction of a body part, a disease related to the presence of radiation-resistant or sound-resistant cells, an infectious disease, an autoimmune disease, neuropathology, cancer, tumors, diseases containing or caused by at least one cancer or tumor cell, skin diseases, endocrine disorders, eye diseases or diseases, intestinal diseases, communication disorders, genetic diseases, nervous system diseases, voice disorders, vulvovaginal diseases, liver diseases, heart diseases, febrile diseases, mood disorders, anemia, preferably iron anemia, and personality disorders.

25. The composition according to claim 24, wherein the cancer or tumor is selected from: organ cancer, hematologic cancer, systemic cancer, adrenal cancer, anal cancer, bile duct cancer, bladder cancer, bone cancer, brain cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, eye cancer, gallbladder cancer, heart cancer, kidney cancer, laryngeal and hypopharyngeal cancer, leukemia, liver cancer, lung cancer, nasal cavity and paranasal sinus cancer, nasopharyngeal carcinoma, neuroblastoma, non-Hodgkin's lymphoma, oral and oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer. Pancreatic and penile cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcoma, skin cancer, small intestine cancer, stomach cancer, testicular cancer, thymic cancer, thyroid cancer, uterine cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenstone macroglobulinemia, infectious tumors, Castle man disease, Ewing family tumors, gastrointestinal carcinoids, gastric cancer, intestinal stromal tumors, myelodysplastic syndrome, pituitary tumors and cancerous diseases such as gestational trophoblastic disease, Hodgkin's disease, Kaposi's sarcoma, malignant mesothelioma and multiple myeloma.

26. The composition according to claim 24, wherein the anemia is selected from: iron deficiency anemia, vitamin deficiency anemia, anemia of chronic disease, aplastic anemia, anemia associated with bone marrow disease, hemolytic anemia, sickle cell anemia, thalassemia, pernicious anemia, Fanconi anemia, sideroblastic anemia, congenital erythropoietic anemia (CDA), diamond-Black Fan anemia, and megaloblastic anemia.

27. The composition of claim 24, wherein anemia is a reduction in the total number of red blood cells (RBCs) or hemoglobin in the blood, or a decrease in the blood's ability to carry oxygen.

28. The composition of any one of claims 1 to 27, wherein the compound is attached to the nanoparticles, and the application of the acoustic waves to the nanoparticles induces the dissociation of the compound from the nanoparticles.

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