Magnetic nanoparticles sequentially irradiated by laser radiation for medical, chemical, biological or cosmetic applications

Abstract

To provide magnetosomes for use in medical, biological, chemical, or cosmetic treatment using sequential laser irradiation.SOLUTION: A use method of magnetosomes to be administered to a body part of an individual, includes: a first step of irradiating the magnetosomes with laser radiation at first power; and a second step of irradiating the magnetosomes with laser radiation of lower power than that in the first step or executing no laser irradiation thereon, where the sequence of the first step and second step is repeated at least once.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] The present invention relates to a method for the introduction of magnetic nanoparticles, in particular magnetosomes, into a body part of an individual and then laser irradiation. This allows the magnetic nanoparticles, especially magnetosomes, to be irradiated with light in succession. This offers several improvements over the method of continuously irradiating the [Background technology]

[0002] Magnetosomes effectively target tumors when they are introduced into the tumor and heated by the application of an alternating magnetic field. It has been shown that magnetosomes destroy bacteria efficiently (Reference 1). their better crystallization, larger size, and / or chain length than their synthetic counterparts. It has also been shown to be efficient due to the sequence.

[0003] However, to reach intensities high enough to heat magnetosomes in body parts The application of alternating magnetic fields is difficult to achieve because it requires the use of large and expensive induction systems. It seems difficult.

[0004] Therefore, this patent application proposes a more compact and cheaper excitation source (laser) than the induction system. ) to develop a method for heating magnetic nanoparticles, specifically magnetosomes, with laser radiation. In addition, magnetic nanoparticles, especially magnetosomes, can be sequentially irradiated with laser light. By irradiating the area, the effectiveness of the treatment can be increased and / or the harmful effects reduced. This can be done. (References) Non-patent document 1 E. Alphandéry et al., ACSNano, 5th edition, pp. 6279-6296, 2011 Non-patent reference 2 Suzuki T. et al. (FEBS Lett., 2007, 581: 3443- 3448) Non-Patent Reference 3 Schuler D. et al., FEMS Microbiology Lett, 1995, 132: 139-145 Non-patent reference 4 Qi et al. PLoSOne. 2012;7(l): e29572) Summary of the Invention

[0005] As used herein, the term "magnetic nanoparticles" refers to nanoparticles that elicit a response when exposed to a magnetic field. The term is meant to include any nanoparticle that undergoes a reaction, where the reaction is i) a non-zero magnetization or saturation ii) Saturation coercivity or magnetization, which increases in strength as the magnetic field strength increases; iii) the nanoparticle magnetic moment coupled to the magnetic field, and / or iv) the magnetic field is spatially inhomogeneous. It may be that nanoparticle motion is selectively induced at certain times.

[0006] The term also includes ferromagnetic, ferrimagnetic, paramagnetic, superparamagnetic, and diamagnetic materials. Suitable non-limiting examples include: i) Fe 2 0 3 , Fe 3 0 4 , Fe 2 0 4 , Fe x Pt y , Co x Pt y , MnFe x O y , CoFe x O y , NiFe x O y , CuFe x O y , ZaFe x O y , and CdFe x O y、 (Naoko where x and v are numbers between 1 and 6, determined by synthesis methods known in the art. ), and / or ii) containing magnetic materials such as Fe, Pt, Au, Ag, Mg, Zn, Ni, or Si. In particular, it contains an overwhelming amount of nanoparticles.

[0007] Such as those made of iron or iron oxide, without the application of an external magnetic field or 1 mT (Tesla ) and nanoparticles that are magnetic in the presence of magnetic fields with strengths of less than 100 nm, such as those made of gold or silver. Special 10 -5 , 10 -3 , in the presence of an external intensity higher than 1 or 10 mT It is possible to distinguish between nanoparticles that have a high molecular weight and nanoparticles that have a high molecular weight.

[0008] As used herein, the term "nanoparticle" refers to a nanoparticle having any dimension, such as length, width, surface, volume, or thickness. At least one dimension of which is within the size range of 0.1-1000 nm, in particular 1-100 This means that it includes nano-sized materials of less than 1 nm.

[0009] As used herein, the term "metal nanoparticle" refers to a nanoparticle having a length, width, surface, volume, or thickness that is greater than or equal to the length, width, surface area, volume, or thickness of the nanoparticle. At least one dimension is in the size range of 0.1-1000 nm, particularly 1-100 This means that any nano-sized metal within the nanometer range is included. In embodiments, the term "metal nanoparticles" refers to any of a number of nanoparticles, such as gold or silver nanoparticles. In some embodiments, the term "metal nanoparticles" is used. The term includes only iron or iron oxide nanoparticles.

[0010] As used herein, the term "plasmonic nanoparticles" refers to plasmonic, plasmonic The present invention includes any nanoparticles that induce surface plasmon waves, surface plasmons, and / or surface plasmon waves. In some embodiments, for example, the magnetic and / or gold nanoparticles Magnetic and / or metallic nanowires are known when the metal properties lead to localization of electrons that give rise to plasmons. The nanoparticles are plasmonic.

[0011] As used herein, the term "mineral nanoparticles" refers to any one of the following: The term "nanoparticles" is meant to include any nanoparticle having at least one of the following characteristics: i) a metal group ii) crystalline compositions; iii) non-organic or non-carbonaceous compositions; iv) compositions that are not oxidized by humans. not implemented in whole or in part, or based on human reasoning, plans, designs, processes, v) compounds derived from organisms, particularly organisms other than humans; and and vi) compounds originating from or occurring in the natural environment, where microbial This natural environment, including growth, can be replicated by humans in some embodiments.

[0012] As used herein, the term "temperature" refers to a step, stage, or duration of a method or treatment according to the present invention. This is meant to include temperatures between steps, sequences, treatment periods, and between treatment periods. In particular, It is meant to include minimum, maximum, and average temperatures as well as temperature gradients. In the state, i) the laser power, ii) the dissociation percentage, and iii) the amount of nuclei generated by the magnetic nanoparticles. The maximum, minimum, average, or gradient of the radical species is given by the maximum, minimum, average temperature and temperature gradient. The term temperature or a term related to temperature is used to describe: i) laser power; ii) percentage of dissociation; iii) The term radical species generated by magnetic nanoparticles, or i) the laser power, ii ) the percentage of dissociation, and iii) the term for the radical species generated by the magnetic nanoparticles. can be defined in a similar manner by selectively replacing

[0013] As used herein, the term "heating" refers to the heating that occurs during the first step. It means to include.

[0014] As used herein, the term "cooling" includes the cooling that occurs during the second step. This means that... As used herein, the term "treatment" refers to a treatment step, a treatment sequence, a treatment session, or the like. "treatment," "treatments," and / or "treatments" are meant to include the entire

[0015] As used herein, the term "method" refers to a method step, sequence, session, or , and / or methods in their entirety.

[0016] As used herein, the term "physiological temperature" refers to the temperature of a healthy individual, optionally It is meant to include the temperature of any part or whole body of such an individual.

[0017] In one embodiment of the present invention, the metal composition is a composition that includes: i) in some cases are 1, 10, 10 per nanoparticle 3 , 10 5 , 10 10 , 10 20 , or 10 50 Exceeding ii) in some other cases 10 metal atoms per nanoparticle 50 , 10 20 , 10 10 , 10 5 , 10 3 , 10, or even less than 1 metal atom; and iii) in some other cases. Selectively select 1 to 10 per nanoparticle. 100 , 1 to 10 50 , 1 to 10 20 , 1 From 10 10 , 1 to 10 5 Between or 1 to 10 3 Metal atoms between the In some cases, the metal composition is a composition that includes: i) in some cases In the case of nanoparticles, the number of atoms or the mass number or the volume is 10 -50 , 10 -10 , 10 -5 , 10 -2 , 10 -1 , 0, 1, 5, 1025, 50, 75, 80, 9 more than 0, 95, 99 or 99.9 percent metal atoms; ii) in some other case In the case of nanoparticles, the number of atoms, mass number, or volume is selectively set to 100, 99.9, 99, 90, 80, 75, 50, 25, 10, 5, 0, 1, 10 -1 , 10 -5 or 1 0 -10 percent or less of metal atoms, and iii) in some other cases, nanoparticles. Selectively, 10 in atomic number, mass number, or volume -50 Between 100 and 10 - 20 Between 100 and 10 -10 between 1 and 100, between 50 and 100, between 10 -50 Between 10 and 99 -20 Between and 99, or 10 -10 Between and 99 percent metal atom.

[0018] In one embodiment of the present invention, the atomic percentage of metal atoms is N MA / N A where N MAis the number of metal atoms in the nanoparticle, N A is the total number of atoms (metallic and nonmetallic) in the nanoparticle. It is a number.

[0019] In one embodiment of the present invention, the mass percentage of metal atoms is M MA / M A where M MA teeth Mass of metal atoms contained in nanoparticles, M A is the mass of all atoms in the nanoparticle.

[0020] In one embodiment of the present invention, the volume percentage of the metal atoms is V MA / V A where V MA teeth The volume occupied by the metal atoms in the nanoparticle, V A is the volume of the nanoparticle, or the nanoparticle is the volume of all atoms contained in

[0021] In one embodiment of the present invention, per nanoparticle means per at least one nanoparticle. do.

[0022] In one embodiment of the invention, a crystalline composition is a composition t hat comprises: i) in some embodiment more than 1, 10, 10 3 , 10 5 , 10 10 , 10 20 , or 10 50 ordered atoms or ordered atomic planes or crystallographic planes or crystallographic planes llographic directions preferentially per nanoparticle, ii) in some other embod less than 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , or 10 ordered atoms or ordered atoms c planes or crystallographic planes or crystallographic directions preferentiall y per nanoparticle preferentially per nanoparticle, iii) in still some other embodiment, between 1 and 10 100 , 1 and 10 50 , 1 and 10 20 , 1 and 10 10 , 1 and 10 5 , or between 1 and 10 3 ordered atoms or ordered atomic planes or crystallographic planes or crystallographic directions preferentially per nanoparticle preferenti ally per nanoparticle. In one embodiment of the present invention, the crystalline composition is a composition consisting of: i) In some embodiments, the nanoparticles may be selectively 1, 10, 10 3 , 10 5 , 10 10 , 1 0 20 , or 10 50 Aligned atoms or aligned atomic planes or crystal planes or crystal orientations exceeding ii) per nanoparticle; ii) in some other embodiments, selectively per nanoparticle. 10 to 50 , 1020 , 10 10 , 10 5 , 10 3 or less than 10 regular atoms or are regular atomic planes or crystallographic planes or crystallographic directions, iii) some In another embodiment, alternatively, 1 to 10 100 , 1 to 10 50 , 1 From 10 20 , 1 to 10 10 , 1 to 10 5 , or 1 to 10 3 Aligned atoms between is an aligned atomic plane or crystallographic plane or crystallographic direction. In the present invention, the crystalline composition is a composition comprising: i) in some embodiments, nanoparticles Selectively 10 per -50 , 10 -10 , 10 -5 , 10 -2 , 10 -1 , 0, 1, 5, More than 10, 25, 50, 75, 80, 90, 95, 99 or 99.9 percent a row of atoms or an aligned atomic plane or a crystallographic plane or a crystallographic direction, ii) some other In the embodiment, the number of nanoparticles per nanoparticle is optionally 100, 99.9, 99, 90, 80, 75, 50, 25, 10, 5, 0, 1, 10 -1 , 10 -5 , or 10 -10 Percentage Alignment a row of atoms or an aligned atomic plane, or a crystallographic plane or a crystallographic direction; iii) any other In an embodiment, optionally 10 nanoparticles -50 -100, 10―20-100, 10 -10-100, 1-100, 50-100, 10-50-99, 10-20-99, or 10-10 or ordered atomic planes or crystal planes or crystal orientations.

[0023] In some embodiments, aligned atoms or aligned atomic planes or crystallographic The percentage of planar or crystallographic directions can be a / b, where α is the surface area of ​​the nanoparticle. is the number of selectively aligned atoms per unit area, the number of crystallographic planes, and the number of crystallographic directions, and β is the number of Selectively, the total number of atoms per particle, the total number of planes, the total number of directions such as elongation direction or orientation, etc. be.

[0024] In some embodiments, the non-organic or non-carbonaceous composition is a minor or minor or low concentration A composition containing carbon or organic or carbonaceous material of the order of 100% or more. The composition may comprise: i) in some embodiments, selective 1, 10, 10 3 , 10 5 , 10 10 , 10 20 , or 10 50 More than 10 carbon atoms, or an organic or carbonaceous material; ii) in some other embodiments, per nanoparticle Selectively 10 50 , 10 20 , 10 10 , 10 5 , 10 3 or less than 10 carbon atoms or an organic or carbonaceous material; iii) in yet some other embodiments, nanoparticles. Select between 1 and 10 100 Between 1 and 10 50 Between 1 and 10 20 Carbon atoms between or organic or carbonaceous materials. In yet some other embodiments, non-organic or The carbonaceous composition is a composition that is comprised of: i) in some embodiments, nanoparticles; Selectively, 10 in atomic number, mass number, or volume -50 , 10 -10, 10 - 5 , 10 -2 , 10 -1 , 0, 1, 5, 10, 25, 50, 75, 80, 90, 95, 9 9 or 99.9 percent carbon atoms or organic or carbonaceous substances; ii) how many In some other embodiments, the number of atoms or mass or volume per nanoparticle may be selected. 100, 99.9, 99, 90, 80, 75, 50, 25, 10, 5, 0, 1, 10 -1 , 10 -5 or 10 -10 percent carbon atoms or organic or carbonaceous matter; iii) In yet some other embodiments, selectively increasing the number of atoms or mass per nanoparticle 10 in number or volume -50 Between 100 and 10 -20 Between 100 and 10 -10 and Between 100, between 1 and 100, between 50 and 100, 10 -50 Between 10 and 99 -20 and Between 99 or 10 -10 Between 99 and 99 percent carbon atoms or organic matter or carbon prime substance.

[0025] In some embodiments, the atomic percentage of carbon atoms is N CA / N A where N CA is the number of carbon atoms in the nanoparticle, and N A is the total number of atoms in the nanoparticle (metal and non-metallic) metal).

[0026] In some embodiments, the mass percent of carbon atoms or organic or carbonaceous materials The culprit is M MC / M A where M MCNanoparticles of carbon atoms or organic matter or is the mass number of the carbonaceous material, M A are the mass numbers of all atoms contained in the nanoparticle. In some embodiments, the volume percentage of carbon atoms or organic or carbonaceous material is , V MC / V A where V MC The carbon atoms or organic matter in the nanoparticles is the volume occupied by the carbonaceous material, and V A is the volume of the nanoparticle or is the volume of all the atoms involved.

[0027] In some embodiments, the crystalline composition is a composition that is comprised of: i) some In some embodiments, selectively 1, 10, 10 3 , 10 5 , 10 10 , 1 0 20 , or 10 50 Aligned atoms or aligned atomic planes or crystal planes or crystal directions exceeding ii) in some other embodiments, selectively 10 per nanoparticle 50 , 10 20 , 1 0 10 , 10 5 , 10 3 or less than 10 aligned atoms or aligned atomic planes or crystal planes or is the crystallographic direction; iii) in yet other embodiments, selectively 1 per nanoparticle and 10 100 Between 1 and 10 50 Between 1 and 10 20 Between 1 and 10 10 Between 1 and 10 5 Between, or 1 and 10 3 Aligned atoms or aligned atomic planes or crystallographic planes or bonds between In yet some other embodiments, the crystalline composition is configured as follows: i) In some cases, the composition is made of 10 -50 , 10 -1 0 , 10 -5 , 10 -2 , 10 -1 , 0, 1, 5, 10, 25, 50, 75, 80, 90 , more than 95, 99 or 99.9 percent aligned atoms or aligned atomic planes or a crystallographic plane or crystallographic direction; ii) in some other embodiments, a nanoparticle Selectively 100, 99.9, 99, 90, 80, 75, 50, 25, 10, 5, 0 per , 1, 10 -1 , 10 -5 , or 10 -10 Percentage of aligned atoms or aligned atomic faces or a crystallographic plane or crystallographic direction; iii) in yet some other embodiments, Selectively, 10 per nanoparticle -50 Between 100 and 10 -20 Between 100 and 10 -1 0 between 1 and 100, between 50 and 100, between 10 -50 Between 10 and 99 -2 0 Between and 99, or 10 -10 Between 100 and 99% aligned atoms or aligned atomic planes or crystallographic plane or crystallographic direction.

[0028] In some embodiments, the "mineral nanoparticles" are composed of a mineral moiety, a selectively predominant mineral the mineral portion, which is optionally the center or heart or core of the nanoparticle; Mineral nanoparticles are characterized as being coated or mixed with non-mineral materials. wherein the non-mineral material is a coating of nanoparticles; or Stabilize, disperse, preserve, conserve, administer, mix, or homogenize the mineral It is a substance that helps to

[0029] In some embodiments, the mineral moiety of interest is in the amount of or represents: i) nano The mass or volume of the mineral part that makes up the particle is 10-50, 10-5, 1, 5, 10, 20, 50, 75, 80, 90, 95, 99 or 99.9 percent or more; ii) other In some embodiments, the mineral moiety constituting the nanoparticles is 100 by mass or volume, 99, 90, 80, 75, 50, 20, 10, 5 or 1 percent; iii) In some other embodiments, the mineral moiety constituting the nanoparticles is about 1 / 2 by mass or volume. 0 -50 Between 100 and 10 -10 between 1 and 100, between 25 and 100, Between 50 and 100, or between 75 and 100 percent.

[0030] In some embodiments, the mass or volume percentage of the mineral moiety contained in the nanoparticles The culprit is M M / M N or V M / V N where M M and M. N are respectively, is the mass of the neural and nanoparticles, and V M and V N are minerals and nanoparticles, respectively. is the volume of.

[0031] As used herein, the term "magnetosome" refers to a magnetosome that surrounds a mineral center and The membrane is completely or partially stabilised to specifically stabilize the central part or to prevent agglomeration or aggregation of the central part. This means that the nanoparticles contain a mineral core surrounded by a magnetic membrane. Membranes, i.e. membranes that are not synthesized by organisms that produce organisms that synthesize the central part in particular, or membranes synthesized by organisms such as magnetotactic microorganisms, the latter of which are composed of lipids, lipopolysaccharides, , endotoxins, and proteins or membrane-associated proteins produced by the microorganisms. The central portion and / or the membrane optionally contain iron oxide or sulfur in the central portion. The membrane is of well-defined composition, such as iron oxide, organic or carbonaceous composition. The magnetic nanoparticle, optionally a magnetosome, optionally a central portion of the magnetic nanoparticle is a magnetosome. Gnetite (Fe 3 O 4 ), iron sulfide (greigite or Fe 3 S 4 ) or their The iron oxide nanoparticles are composed of a mixture of magnetite and iron oxide. In practice, magnetosomes can be oxidized to maghemite after extraction from bacteria. The magnetic nanoparticles, optionally magnetosomes, are a mixture of magnetite and maghemite. may include.

[0032] Magnetosomes offer a series of advantages over other types of nanoparticles: i) better heating properties; ii) less agglomeration and more adhesion to their surfaces; iii) lower toxicity; iv) less toxic effects; A manufacturing method that allows the use of fewer compounds.

[0033] "Magnetic nanoparticles", in particular magnetosomes, can refer to: i) "magnetic Chains of magnetic nanoparticles, especially magnetosomes Magnetic nanoparticles, especially magnetosomes, are magnetotactic nanoparticles. They can be arranged in chains within the bacteria or after their extraction or separation, making them more suitable for use with other types of proteins. Nanoparticles of this type do not spontaneously grow without the application of an external magnetic field, which is usually much stronger than the Earth's magnetic field. In contrast, the magnetic nanoparticles are not thought to be arranged in chains. Particles, particularly magnetosomes, can be membrane-free, e.g. when the membrane is partially or completely removed. In some other embodiments, the magnetic nanoparticles may be configured with a central portion without a membrane. Molecules, especially magnetosomes, can be easily removed, for example if the central part is partially or completely removed. It consists of a membrane without a central portion.

[0034] The term "synthetic organism" refers to any organism that can synthesize metal-rich nanoparticles. Such organisms are intended to include, in particular, cells, in particular eukaryotic or prokaryotic cells, bacteria. , collections of cells, fish, birds, mammals, plants, trees, fungi, archaea, shellfish, or enzymes, proteins The nucleic acid is selected from a part of a living organism, such as a protein, DNA, RNA, or biological material. Such organisms are optionally non-human. In some embodiments, synthetic organisms are used in a variety of applications, such as enzymatic reactions. By reaction or interaction between biological material and metals that selectively leads to the formation of nanoparticles. Depending on the action, nanoparticles are synthesized intracellularly or extracellularly.

[0035] As used herein, the term "magnetotactic microorganism", which is equivalently designated as "magnetotactic bacteria", refers to To synthesize iron-rich particles, especially within cells, which may be arranged in chains of 2 to 100 particles. The presence of these particles is intended to include any microorganism capable of perpetuating a particular The magnetic properties of these microorganisms are This can allow objects to be oriented specifically parallel to the Earth's magnetic field. Suitable magnetotactic microorganisms capable of this include, but are not limited to: Nitrospira, Nitrospira moscoviensis, Magnetobacterium bavaricum, Desulfovibrio m agneticus RS-1, Desulfovibrio desulfuricans, Geobacter metallireducens, d-Protob acteria, MMP5, MMP2, where MM designates magnetotactic many-celled prokaryote, m agnetic cossus, MC-1, CS103, NKMC5, a-Protobacteria, Rhodospirillum rubrum, Agrobacterium vitis, Magnetospirillum ma gnetotacticum MS-1, Magnetospirillum magneticum AMB-1, Magnetospirillum magnetic um MGT-1, Magnetospirillum gryphiswaldense MSR-1, marine magnetic vibrio MV-1, M agnetospirillum gryphiswaldense MSR- 1, Magnetospirillum magneticum AMB-1, Magne tospirillum magnetotacticum MS-1, Magnetospirillum magneticum strain MGT-1, magn etotactic coccus strain MC-1, Desulfovibrio magneticus RS-1 and anaerobic vibrio strains MV-1, MV-2 and MV-4. Nitrospira, Nitrospira moscoviensis, Magnetotactic bacteria bavaricum, Desal Phovibrio magneticus, RS-1, Desulfovibrio desulforicans, Di Ovacter metallidusens, δ-protobacteria, MMP5, MMP2, where MM is chemotactic Magnetic multicellular prokaryote refers to multicellular prokaryotes, CS103, NKMC5, α-proteobacteria; Rhodospirillum rubrum, Agrobacterium vitis, Magnetospirillum Magnetotacticum MS-1, Magnetospirillum magneticum AMB-1, Magnetospirillum Magnetospirillum magneticum MGT-1, Magnetospirillum griftiswaldens MSR-1, Sea Western magnetic vibrio MV-1, Magnetospirillum magneticum AMB-1, Magnetospirillum Magnetotacticum strain MGT-1, Magnetotactic cocci strain MC-1, Desulfovibrio O. magneticus RS-1 and the anaerobic Vibrio strains MV-1, MV-2 and MV-4. Suitable methods for determining whether an object is magnetotactic include, but are not limited to, However, i) the determination of the total iron, especially crystallized iron, content in these microorganisms, e.g. absorption spectrophotometry or inductively coupled plasma mass spectrometry or iron dosage as described in reference 2; ii) C using light scattering techniques mag Determination of parameter values ​​(see non-patent reference 3); iii) As described in non-patent reference 4, images of these microorganisms taken with a transmission electron microscope (Non-Patent Reference 4) (See patent reference 4).

[0036] As used herein, the term "sequential laser irradiation" refers to a method in which lasers are sequentially The term "laser irradiation" is intended to include any method by which the nanoparticles are irradiated with laser light. The first step is when the laser output is turned on, and the second step is when the laser power is turned on. and a second step in which the power is turned off or at a lower power than during the first step. The first and second steps are performed in one sequence, and the sequence is Each sequence is repeated once, and a combination of several sequences constitutes a session. The period between sessions is usually long, optionally longer than 30 minutes, e.g. to allow the patient to rest. However, the duration of the steps or sequences or the duration between steps and sequences is usually Usually short, preferably less than 30 minutes, until the treatment or method is particularly effective. This allows for a sufficiently large number of repetitions of a step or sequence. The "sub-laser irradiation method" is selectively different from the "continuous laser irradiation method". The laser does not include steps or sequences and consists of continuous laser irradiation, i.e., a session Do not turn off the power or reduce the laser output during scanning. By using sequential laser irradiation instead of the single shot method, several Several advantages may result: i) the average temperature reached during treatment by the sequential method is much lower than that achieved by the continuous method; ii) In sequential methods, the The process temperature must be stable at a constant temperature for the majority of the duration of the heating cycle. This can be a difficult task for humans because the heating temperature of body parts It accurately and continuously measures the temperature and adjusts the laser power to maintain the temperature at the desired value. iii) In the sequential method, the first and second steps are During the step, a temperature gradient occurs, which is particularly useful for destroying pathological or tumor cells. This can be more efficient at reducing the temperature and produce more energy than maintaining a constant temperature for most of the heating. and / or iv) the laser power required to perform the sequential method. Alternatively, the current or intensity may be lower than that required to carry out a continuous process.

[0037] In one embodiment of the present invention, the nanoparticles are at least one selected from the group consisting of: They have three properties: i) they are magnetic, ii) they are minerals, and iii) they are partially or completely synthesized by organisms other than humans, iv) they They are metallic, v) they are plasmonic, and iv) they are magnetosomes. be.

[0038] In one aspect of the invention, the present invention provides a method for the treatment of medical, biological or chemical disorders by sequential laser irradiation. The present invention relates to magnetic nanoparticles, in particular magnetosomes, for use in medical or cosmetic treatments, In this study, magnetic nanoparticles, specifically magnetosomes, are administered to an individual's body parts. - In the first step, magnetic nanoparticles, specifically magnetosomes, are exposed to laser radiation with a first power. And then irradiate - In the second step, magnetic nanoparticles, especially magnetosomes, are subjected to a lower yield than in the first step. by irradiating the target with high-power laser radiation or by laser irradiation of magnetic nanoparticles, in particular magnetosomes. No irradiation is performed, and The sequence of the first and second steps is repeated at least once.

[0039] In one embodiment of the present invention, the laser radiation at the first power is This is done with the laser power during the first or second step.

[0040] In another embodiment of the present invention, the laser radiation at the second power is The laser power during the first or second step is then adjusted.

[0041] In one aspect, the present invention provides a method for the treatment of medical, chemical or biological diseases by sequential laser irradiation. The present invention relates to magnetic nanoparticles, in particular magnetosomes, for use in medical or cosmetic treatments. - Magnetic nanoparticles, specifically magnetosomes, are administered to an individual's body parts, and - In the first step, magnetic nanoparticles, specifically magnetosomes, are irradiated with a laser beam. do - In the second step, magnetic nanoparticles, in particular magnetosomes, are charged with the magnetic nanoparticles in a manner similar to that in the first step. The magnetic nanoparticles are then irradiated with a lower power laser, or the magnetic nanoparticles are irradiated with a laser. No. And The sequence including the first and second steps is repeated at least once.

[0042] In one aspect of the invention, the present invention provides a method for the medical and biological treatment of body parts of an individual by sequential laser irradiation. and - administering an effective amount of magnetic nanoparticles to a body part of an individual in need thereof; and - Exposing the magnetic nanoparticles to sequential laser irradiation including the following steps: i) a first step including irradiating the magnetic nanoparticles with laser radiation at a first power. Execute the steps of ii) not irradiating the irradiated magnetic nanoparticles obtained from the first step or a second step including irradiating with laser radiation at a second power output lower than the first power output. Optionally, iii) Repeat one or two steps in at least one sequence .

[0043] In some embodiments, the first power of the laser radiation is P 1 of laser radiation is specified as The second power is P 2 is specified as

[0044] In one embodiment, P 1 or P 2 is 10 -50 , 10 -10 , 10 -5 , 10 -2 , 1 0 -1 , 1, 5, 10, 10 3 Watts greater than cm of body parts 3 Watts per or watts per gram of magnetic nanoparticles.

[0045] In some other embodiments, P1 or P2 is 10 50 , 10 10 , 10 5 , 10 2 , 10, 5, 2, 1, 10-1, 10-3 or 10-5 watts, cm of body parts 3 The power density is expressed in watts per gram of magnetic nanoparticles.

[0046] In some other embodiments, P1 or P2 is 10 -50 From 10 50 Between 10 - 20 From 10 20 Between 10 -10 From 1010 Between 10 -5 From 10 5 Between 10 - 3 From 10 3 Between or 10 -1 Between 10 and 10 watts, especially cm of body parts 3 Win , or watts per gram of magnetic nanoparticles.

[0047] In some other embodiments, P 1 Heat the magnetic nanoparticles at 0 watts or less. This is the value that will be used.

[0048] In some embodiments, P 2 is equal to or close to 0 watts, or This is a value that does not result in heating of the magnetic nanoparticles.

[0049] In some other embodiments, P1 and / or P2 are sufficiently small, and preferably less than 105 , 103, 102, 10, 5, 2, 1 or 10-1 watts, or cm of a particular body part Preferably, the watts per watt are less than 3, thereby eliminating the need for magnetic nanoparticles. No body parts will be heated.

[0050] In some other embodiments, P1 is stable throughout the first step. In this case, P1 can optionally vary by less than 100, 75, 50, 30, 20, 10, 5, 2 or 1% This percentage is in particular equal to (P1max-P1min) / P1ma, where P1max and dP1min are the first These are the maximum and minimum values ​​of the laser output for one step.

[0051] In some other embodiments, P 2 is stable over the second step. In this case, P 2 Selectively vary by less than 100, 75, 50, 30, 20, 10, 5, 2 or 1% And this percentage is especially (P 2max - P 2min ) / P 2max is equal to. Here, P 2max and P 2min are the maximum and minimum values ​​of the laser power in the second step.

[0052] In some other embodiments, P 1 is unstable over the first step. In this case , P1 is selectively 10 -10 , 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 50, 7 The percentages vary from 5, 80, 90, or 95%, and this percentage is especially important for 1max -P 1min ) / P 1max To where P 1max and P 1min are the maximum and minimum values ​​of the laser power in the first step It is.

[0053] In some other embodiments, P 2 is unstable over the second step. In this case , P 2 is selectively 10 -10 , 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 50, 75, 80, 90 or more than 95% This ratio varies in particular with the following value: (P 2max -P 2min ) / P 2max , where P 2max and P 2min are the maximum and minimum values ​​of the laser power in the second step.

[0054] In some embodiments, the laser power is a maximum of 1000 Hz for the first or second step. Or the minimum laser output.

[0055] In one embodiment of the present invention, sequential laser irradiation is used to treat individual body parts for medical or biological purposes. Or cosmetically treating means treating an individual's body parts by: i) subjecting the solid body part to sequential laser irradiation, the body part being coated with magnetic nanoparticles; ii) exposing the magnetic nanoparticles to sequential laser irradiation; and iii) exposing the sequential irradiation to the magnetic nanoparticles. applied to body parts or magnetic nanoparticles.

[0056] In one embodiment of the present invention, the laser radiation is the same as the laser irradiation, and in particular the magnetic nanoparticles or specifies laser radiation of body parts or application of magnetic nanoparticles or laser radiation to body parts will be done.

[0057] In one embodiment of the present invention, the sequential laser irradiation is performed by applying a sequence defined in the present invention. It's the same.

[0058] In one embodiment of the present invention, the effective amount of magnetic nanoparticles is a therapeutic, cosmetic, or diagnostic effect. Nanoparticles capable of producing a blocking effect or that may be useful in the methods of the present invention. In particular, if the amount of magnetic nanoparticles is different from the effective amount, the treatment according to the invention may be inefficient. For example, magnetic nanoparticles in amounts less than the effective amount do not generate heat under laser irradiation. For example, amounts of magnetic nanoparticles greater than the effective amount may be toxic. do.

[0059] In one embodiment of the present invention, the magnetic nanoparticles are not irradiated, in particular prior to laser irradiation. or without irradiation.

[0060] In another embodiment, the magnetic nanoparticles are specifically irradiated during, after or simultaneously with the laser irradiation. .

[0061] In one embodiment of the present invention, the treatment is selected from the group comprising: i) this medical, biological (ii) this laser treatment; (iii) this disease treatment; (iv) this treatment steps of this treatment sequence; and, vi) this treatment session, step, or sequence. and the whole treatment consisting of sessions, vii) this method, and viii) this treatment method.

[0062] In one embodiment of the present invention, the biological or chemical treatment involves a biological or chemical agent. However, it may not necessarily be a medical treatment, for example, the nanoparticles may be biological When mixed with a biological or chemical substance and treated by the method, it is To soften biological substances, to detect them, biological or chemical materials carried out to change the composition or structure of a biological or chemical substance in order to color it There are times when this happens.

[0063] In one embodiment of the present invention, a cosmetic procedure refers to an improvement in an individual's appearance that is not necessarily a medical procedure. For example, the treatment may be a treatment that does not involve the destruction or detection of at least one cell. However, this may result in, for example, changing an individual's skin color.

[0064] In one embodiment of the invention, the medical treatment comprises the treatment of at least one cell, particularly a pathological cell. The treatment may result in the detection or destruction of

[0065] In another aspect of the present invention, the present invention provides a method for sequentially irradiating magnetosomes with a laser. This is about a method for In a first step, the magnetosomes are irradiated with laser radiation, and - In the second step, the magnetosomes are exposed to a lower power than in the first step. Laser irradiation or no laser irradiation of magnetosomes, and The sequence of steps 1 and 2 is repeated at least once.

[0066] In another aspect of the invention, the present invention provides a method for administering an effective amount of magnetosomes to a body part of an individual. 2. A method for treating an individual with sequential laser irradiation, comprising: - in a first step, irradiating magnetic nanoparticles, in particular magnetosomes, with laser radiation, and - In the second step, the magnet is generated by irradiation with a lower power laser than in the first step. The magnetosomes are irradiated with a magnetic nanoparticle, in particular a magnetosome, or the magnetosomes are irradiated with a laser. The sequence of steps 1 and 2 is repeated at least once. will be done.

[0067] In one embodiment of the present invention, the magnetic nanoparticles share at least one property in common with magnetosomes. has.

[0068] In the present invention, the "first step" and the "second step" are repeated at least once. The sequence corresponds to a series of sessions, some of which correspond to a therapy session. A series of "treatment sessions" corresponds to the entire treatment.

[0069] In one aspect, the present invention relates to magnetic nanoparticles for use according to the present invention, The magnetic nanoparticles are mineral nanoparticles, in particular magnetosomes, and / or magnetic Nanoparticles are synthesized by synthetic organisms, in particular magnetotactic microorganisms,

[0070] In one aspect, the present invention relates to magnetic nanoparticles for use according to the present invention, Here, magnetic nanoparticles are magnetic nanoparticles synthesized by living organisms, in particular by magnetosomes. It is a particle.

[0071] In one aspect of the invention, the present invention provides magnetosomes, or magnetosomes, for use according to the invention. The method according to the invention, in which the netosomes are synthesized by an organism, in particular a homologous bacterium. do.

[0072] In one embodiment of the present invention, the organism that synthesizes the magnetic nanoparticles is a synthetic organism, which is particularly suitable for human This is especially true for microorganisms such as magnetotactic microorganisms.

[0073] In particular, the magnetotactic microorganism may be a magnetotactic bacterium.

[0074] In one embodiment, the magnetic nanoparticles of the present invention are mineral nanoparticles, preferably magnetosomes. It is.

[0075] In one embodiment, the magnetic nanoparticles of the present invention are synthesized by synthetic organisms, preferably magnetotactic microorganisms. It is synthesized.

[0076] In another embodiment of the invention, the magnetic nanoparticles are at least one different from those of the magnetosomes. It has one characteristic.

[0077] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are 1, 10, 10 2 , 1 0 3 , 10 5 , 1010 , 10 20 , or 10 50 At least one magnetic nanoparticle, particularly a magnet The cells can be characterized by aggregates that contain tosomes.

[0078] In yet another embodiment of the present invention, the magnetic nanoparticles, particularly magnetosomes, are 10 2 , 10 3 , 10 5 , 10 10 , 10 20 , or 10 50 Magnetic nanoparticles, especially These can be characterized by assemblies that contain magnetosomes in their outermost layer.

[0079] In yet another embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are -50 , 10 -40 , 10 -30 , 10 -20 , 10 -10 , 10 -5 , 10 -3 , 1, or 1 0 2 The present invention can be characterized by an assemblage consisting of: i) magnetic nanoparticles; ii) magnetic nanoparticles, in particular magnetosomes, containing mg of iron or iii) mg of magnetic nanoparticles, in particular magnetosomes, in 1 cm 3 Including or iv) mg of magnetic nanoparticles, specifically magnetosomes, in 1 cm 3 of, or v) mg 1cm of iron 3 or vi) magnetic nanoparticles, in particular magnetosomes, containing per mg of iron Magnetic nanoparticles, especially magnetosomes, are 1 cm 3 Included per body part.

[0080] In yet another embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are -50 , 10 -40 , 10 -30 , 10 -20 , 10 -10 , 10 -5 , 10 -3 , 1, 10 2 , 10 5 , 10 10 or 10 20 Characterized by a set that includes less than i) mg of magnetic nanoparticles, in particular magnetosomes, or ii) mg of iron-containing magnetic nanoparticles. iii) mg of magnetic nanoparticles, in particular magnetosomes; or iv) mg of magnetic nanoparticles, in particular magnetosomes. 1cm 3 or iv) mg of magnetic nanoparticles, in particular magnetosomes, in 1 c of a body part. m 3 per milligram of iron-containing magnetic nanoparticles, specifically magnetosomes, per cm 3 Per or vi) administering mg of iron-containing magnetic nanoparticles, in particular magnetosomes, to 1 cm of the body part. 3 Around.

[0081] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, as defined herein are Such compounds may be wrapped, joined, or tied together.

[0082] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, have at least one of the following properties: i) a core, particularly a magnetic material, particularly a mineral, in particular Contains iron oxide, most particularly maghemite or magnetite, or maghemite ii) the presence of an intermediate composition between magnetite and ZnO; and ii) the presence of a core of magnetic nanoparticles, especially magnetosomes. and selectively prevents aggregation of magnetic nanoparticles, particularly magnetosomes, and in particular of magnetic nanoparticles. The administration of magnetic nanoparticles, in particular magnetosomes, into living organisms or into body parts is possible. The presence of a coating to stabilize the nuclei, where the coating thickness is, in particular, 0.1 nm-1 Between 0μm, between 0.1nm-1μm, between 0.1nm-100nm, between 0.1nm-10 nm or between 1 nm and 5 nm; iii) diamagnetic, paramagnetic, superparamagnetic; A magnetic property that results in ferromagnetic or ferrimagnetic behavior or properties. iv) A coercive force of 0.01 , 0.1, 1, 10, 100, 10 3 , 10 4 , 10 5 , 10 9 , or 10 20 Oe v) the ratio between remanent magnetization and saturation magnetization is 0.01, 0.1, 0.2, 0.3, 0. 4, 0.5, 0.75, 0.9, or 0.99, or greater; vi) saturation magnetization is 0.1 , 1, 5, 10, or greater than 50 emu / g; vii) coercivity, remanence, and saturation Magnetic properties such as saturation magnetization are especially important at 0.1K, 1K, 10K, 20K, 50K, 100K, and 2 Measured or observed at temperatures greater than 00K, 300K, 350K, or 3000K, viii) crystalline, i.e. magnetic nanoparticles, in particular magnetosomes, in particular at least one , 5, 10, or 100 crystal faces that are specifically visible or that can be seen by electron microscopy. ix) the presence of single domains, with sizes of 0.1, 0.5, 1.5, as determined by microscopy; , 10, 15, 20, 25, 30, 50, 60, 70, 80, 100, 120, 150, or greater than 200 nm; xi) between 0.1 nm-10 μm in size; Between 1μm, Between 0.1nm-100nm, Between 1nm-100nm, or Between 5nm-8 xii) non-pyrogenic or non-pyrogenic, which is particularly the case for magnetic nanoparticles, especially ma Gnetosomes are magnetic nanoparticles, specifically per mg of magnetosomes, or magnetic nanoparticles , especially 10,000, 1,000, 100, 50, per mg of iron contained in magnetosomes Have an endotoxin concentration of less than 10, 5, 2, or 1 EU (endotoxin unit) or after administering magnetic nanoparticles, particularly magnetosomes, to a living body or a part of the body, In particular, magnetic nanoparticles, especially magnetosomes, can reach temperatures of 100, 50, 10, 6, 5, 3, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 220, 240, 280, 300, 320, 360, 380, 400, This means that it will not cause an initial heating or temperature rise of more than 100 °C. i) synthesis by synthetic organisms, in particular magnetotactic bacteria, which are in particular extracted from magnetotactic bacteria and have magnetic properties Mineral magnetism of nanoparticles, particularly magnetosomes, particularly magnetic nanoparticles, particularly magnetosomes xiv) Synthetic biology leads to the production of only, mostly, or mainly the core. xv) Presence of less than 50, 25, 15, 10, 5, 2, or 1% organic or carbonaceous matter present in the cubic xvi) magnetic nanoparticles, especially magnetospheric nanoparticles, The ratio between the length and width of the magnetic field, the ratio between the longest and largest ends, or the ratio between the magnetic nanoparticles, especially the magnetosphere The ratio of the two different ends, dimensions, especially the intersecting dimensions, or diameters of a thom is 10. ―3 and 1 0 3 , 10 ―2 and 10 2 , 10 ―1 and 10, 0.5 and 5, 0.2 and 2, or 0.1 and 1 or xvii) of mineral substances of synthetic biological origin. xvi) presence of more than 99, 95, 80, 70, 60, 50, or 25% of magnetic Nanoparticles, especially magnetosomes, are available at 1, 10, 1000, or 104 watts per gram. Specific Absorption Rate (SAR) higher than that of conventional laser irradiation, where SAR is measured under irradiation by laser radiation. can be.

[0083] In one embodiment of the present invention, the heating rate of the magnetic nanoparticles is determined by the temperature increase ΔT HS and the duration of the heating step D HS The ratio ΔT between HS / D HS The steps are: It is preferably the difference between the maximum and minimum temperatures of the heating step.

[0084] In another embodiment of the invention, the heating rate of the magnetic nanoparticles is increased above the temperature at the start of the heating step. Rise Δε HS and the duration of the start of the heating step d HS The ratio ΔT between HS / d HS is The start of the heating step occurs within the first few seconds or the first few percent of the duration of the heating step. This specifically represents the

[0085] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are preferably at least 10 ... When measured in kilometres per second, ー20 , 10 ―10 , 10 ―5 , 10 ―3 , 10 ―1 , 1, 5, 10, 10 3 or 10 5 Heating rates higher than 100°C, especially measured per mg of nanoparticles When set, it is 10 ―10 °C, most preferably measured per mg of nanoparticles 10 per second ―5It is characterized by a heating rate higher than 100 °C.

[0086] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are preferably at least 10 ... When measured in degrees, it is 10 times faster than the 20 , 10 10 , 10 5 , 10 3 , 10, 1, 10 ―1 , 10 -3 or 10 ―5 Heating rates below 100°C resulted in a particularly When measured, 10 10 °C or less, most preferably specifically measured per mg of nanoparticles 10 per second 5 It can be characterized by a heating rate of less than 100 °C.

[0087] In one embodiment, the heating rate exists under conditions where the nanoparticles are exposed to the laser at :i) 10 5 , 10 3 , 100, 50, 10, 5, 1 or 10 ―1 Less than watts or Nanoparticle body parts cm 3 Or cm 2 or watts per cm or gram, or ii) the temperature of a body part that does not contain nanoparticles when exposed to a laser. No degree increase or cm of body parts 3 ,cm 2 , especially 10 per cm or gram 5 , 10 3 , 100, 50, 20, 10, 5, 2, 1 or 0.1°C lower temperature rise The power required is sufficiently low.

[0088] In some other embodiments of the present invention, the heating rate is such that the nanoparticles are heated at a rate of, in particular, 10 -10 , 10 -5, 10 -1 101, 5, 10 watts or cm of nanoparticles body parts 3 or cm 2 or cm or to induce a temperature rise in nanoparticles with laser powers higher than watts per gram. It exists under conditions of exposure to a laser of sufficiently high power.

[0089] In one embodiment of the present invention, the cooling rate of the magnetic nanoparticles is determined by the temperature drop ΔT CS and the duration of the cooling step D CS The ratio ΔT between CS / D CS where the cooling stage The temperature drop of the step is specifically the difference between the maximum and minimum temperatures of the cooling step.

[0090] In another embodiment of the present invention, the cooling rate of the magnetic nanoparticles is controlled by the temperature drop at the start of the cooling step. Lower ΔT CS and the duration of the cooling step d CS The ratio ΔT between CS / d CS It is. The start of the cooling step is particularly important during the first few seconds or first few percent of the duration of the cooling step. Represents the

[0091] In one embodiment, the magnetic nanoparticles, particularly magnetosomes, are measured per mg of nanoparticles. Especially when the -20 , 10 -10 , 10 -5 , 10 -3 , 10 -1 , 1, 5, 1 0, 10 3 or 10 5 Cooling rates higher than 100°C, preferably measured per mg of nanoparticles 10 per second -5 °C or higher, most preferably 10 -3 ℃ higher cooling rate It is characterized by the above.

[0092] In one embodiment, the magnetic nanoparticles, particularly magnetosomes, are measured per mg of nanoparticles. Especially when the 20 , 10 10 , 10 5 , 10 3 , 10, 1, 10 -1 , 10 -3 or 10 -5 °C or less, preferably when measured per mg of nanoparticles , less than 10°C per second, most preferably less than 10°C per second 5 The cooling rate is less than 100°C.

[0093] In one embodiment, the cooling rate is such that the nanoparticles are not exposed to a laser or heating step. Laser power of at least 0, 1, 1.1, 1.5, 2, 5, 10, 10 3 , 10 5 or 10 10 This exists under conditions of exposure to laser powers that are a factor of .

[0094] As shown in the experimental examples, typical heating rates are 0.2-0.05% per milligram of nanoparticles per second. The cooling rate is typically 0.1°C per milligram of nanoparticles per second. In some cases, the different values ​​of the heating or cooling rates are preferably 0, 1, 1.1, 1.5, 2, 5, 10, 10 3 or 10 5 A higher factor is achieved by: i) ii) changing the laser power; or iii) changing the nanoparticle concentration. Adjust nanoparticle size, size distribution, coating, surface-to-volume ratio, or nanoparticle crystallinity thing.

[0095] In one embodiment of the present invention, the duration of the cooling step is longer than the duration of the heating step. Preferably at least 0, 1, 1.1, 1.5, 2, 5, 10, 10 3 or 10 5 Double, Preferably, the amount of the nanoparticles is at least 2 times less, more preferably at least 5 times less. Heat generation occurs at the surface, which causes heat transfer between the nanoparticle surface and the environment or surroundings of the nanoparticle. This may be especially true when heat transfer is facilitated.

[0096] In one embodiment of the present invention, the nanoparticles are irradiated with a laser, particularly in the heating step. Thus the difference between the maximum temperature reached and the temperature reached at the end of the heating step is 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , 10 2 , 10, 5, 2, 1, 10 -1 or 10 -3 ℃, preferably less than 5 ℃, most preferably less than 1 ℃. Such a difference is The nanoparticles remain after the laser is turned off (or power is reduced) at the end of the heating step. This can happen if the heat is continued.

[0097] In one embodiment of the present invention, the duration of irradiation of the laser at a given power and the body during this laser irradiation are The difference in the elapsed time during which the parts are heated is 10 5 , 10 3 , 10, 5, 2, 1. or 1 0 -3 Less than 10 seconds, preferably 3 The time required for the laser to reach the desired target temperature is less than 10 seconds, and most preferably less than 10 seconds. When the nanoparticles stop or reduce heating after switching off or reducing power Such differences can occur when the laser is turned off (or This can happen if the nanoparticles continue to heat up after the power is reduced.

[0098] In some other embodiments of the present invention, the nanoparticles are subjected to a laser, particularly within the heating step. The difference between the maximum temperature reached by irradiation and the temperature reached at the end of the heating step is higher than 10-50, 10-20℃. 10-10, 10-5, 10-3, 10-2, 1, 5, 10 or 103°C, preferably 10-20°C or higher, most preferably 10- Higher than 2°C.

[0099] In one embodiment of the present invention, the duration of irradiation of the laser at a given power and the body during this laser irradiation are The difference in the elapsed time during which the parts are heated is greater than 105, 103, 10, 5, 2, 1. 10-3, 10-5, 10-10 or 10-20 seconds, preferably less than 10-5 seconds. long, most preferably longer than 10-3 seconds. This is done after the laser is switched off and This can occur when nanoparticles do not stop or reduce heating after the power is turned down or the temperature is increased.

[0100] In one embodiment, the number of sequences of the first step and the second step increases, preferentially by a factor of at least 0, 1, 5, 10, 10 3 or 10 5 , when the nanoparticle concentration increases, preferentially by a factor of at leas t 0, 1, 5, 10, 10 3 or 105 . In one embodiment, increasing the nanoparticle concentration reduces the sequence of the first and second steps. In particular, the number of instances is at least 0, 1, 5, 10, 3 or 10 5 twice as much, preferably At least 0, 1, 5, 10, 10 3 , or 10 5 decreases by a factor of two.

[0101] In one embodiment, the nanoparticle concentration is particularly at least 0.1, 5, 10, 10 3 or 10 5 of When the heating rate is increased by a factor of at least 0, 1, 5, 10, 10 3 or 10 5 It increases by a factor of .

[0102] In one embodiment, the cooling rate is adjusted so that the nanoparticle concentration is 0.1, 5, 10, 10 3 or 10 5 Double Increases, especially at least 0.1, 5, 10, 10 3 or 10 5 The decrease is 2x.

[0103] In one embodiment, the number of sequences of the first and second steps is 1, 5, 10, 100 times per second, minute, hour, day, month or year 3 , 10 5 or 10 10 There may be many sequences.

[0104] In some other embodiments, the sequence number of the first step and the second step is nanoseconds. Specifically 10 per milligram of particles, per second, minute, hour, day, month or year 10 , 10 5 , 10 3 , 10, 5 or even less than 1 sequence.

[0105] In another embodiment of the invention, the magnetic nanoparticles, in particular magnetosomes, have one of the following properties: The nanoparticles are characterized by at least one of: i) a coercivity of 0.01, 0.1, 1, 10, 100; 10 3 , 10 4 , 10 5 , 10 9 , or 10 20 Oe, ii) the ratio of remanent magnetization to saturation magnetization is 0. 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 0.9, or less than 0.99 iii) the saturation magnetization is 0.1, 1, 5, 10, 50, 200, 1000, or 5000 emu / g or less; iv) magnetic properties are below 0.1K, 1K, 10K, 20K, 50K, and 100K. Specifically measured or observed at temperatures below 200K, 300K, 350K, or 3000K viii) the sizes are 0.1, 0.5, 1.5, 10, 15, 20, 25, 30, smaller than 50, 60, 70, 80, 100, 120, 150, or 200 nm; and ix) The presence of organic or carbonaceous materials of synthetic biology is 50, 25, 15, 10, 5, 2 x) Presence of less than 99, 95, 80, 70, or more than 1% of synthetic biogenic microorganisms. The presence of neural substances is 99, 95, 80, 70, 60, 50, or 25% complete, or ) magnetic nanoparticles, in particular those whose specific absorption rate (SAR) is measured under irradiation with laser radiation; Magnetosomes per gram: 1, 10, 1000, or 10 4 Less than a watt.

[0106] In one embodiment of the invention, the nanoparticles are metallic. In particular, the metallic nanoparticles comprise at least 1, 10, 10 3 , 10 5Or 10 9 or at least one metal atom , 10, 50, 75 or 90% of the metal atoms in the nanoparticles, is the number or mass of metal atoms in the nanoparticle divided by the total number or mass of all atoms in the nanoparticle. .

[0107] In one embodiment, the nanoparticles, particularly metal oxide nanoparticles, also have a molecular weight of at least 1, 10, 1 0 3 , 10 5 Or 10 9 or at least 1, 10, 50, It can contain 75 or 90% oxygen atoms, where this percentage is the nano The ratio of the number or mass of oxygen atoms in a particle divided by the total number or mass of all atoms in the nanoparticle. be.

[0108] In one embodiment, the atom may be a chemical element or an element.

[0109] In another embodiment of the present invention, the metal or metal atom is selected from the list consisting of: , lithium, beryllium, sodium, magnesium, aluminum, potassium, calcium Cr, Scandium, Titanium, Vanadium, Chromium, Manganese, Iron, Cobalt, Nickel , and nickel, copper, zinc, gallium, rubidium, strontium, yttrium, Zirconium, niobium, molybdenum, technetium, ruthenium, rhodium, palladium , silver, cadmium, indium, tin, cesium, barium, lanthanum, cerium, platinum Theodymium, neodymium, promethium, samarium, europium, gadolinium, terbium , dysprosium, holmium, erbium, thulium, ytterbium, lutetium Zn, Hafnium, Tantalum, Osmium, Osmium Iridium, Platinum, Gold, Mercury, Lithium, Lead, Bismuth, Polonium, Francium, Radium, Actinium, Thorium , Protactinium, Uranium, Neptunium, Plutonium, Americium, Curium , berkelium, caliphormium, einsteinium, fermium, mendelebi Um, nobelium, lawrencium, rutherfordium, dubnium, seaborgium , Borium, Hassium, Meitnerium, Darmstadtium, Roentgenium, Copper Nisium, Nihonium, Flerovium, Moscovium, and Livermorium or Livermo Lithium atom.

[0110] In another embodiment of the invention, the nanoparticles are 1, 10, 10 3 , 10 5 Or 10 9 Less than It contains metal atoms or contains less than 1, 10, 50, 75 or 90% metal atoms. Here, % is the number or mass of metal atoms in the nanoparticle, and % is the total number or mass of all atoms in the nanoparticle. This is the ratio divided by .

[0111] It's 1, 10, 10 3 , 10 5 Or 10 9 It may also contain less than 100 oxygen atoms. or less than 1, 10, 50, 75 or 90% oxygen atoms, The percentage of oxygen atoms in a nanoparticle is calculated by dividing the number or mass of oxygen atoms in the nanoparticle by the total number of atoms in the nanoparticle. It is divided by a number or mass.

[0112] In one embodiment, the nanoparticles comprise a metal oxide or a metal and oxygen atoms. In one embodiment of the present invention, a nanoparticle is magnetic when it has magnetic behavior or properties. The magnetic behavior or properties are diamagnetic, superparamagnetic, paramagnetic, ferromagnetic, and ferrimagnetic. The characteristic is specifically selected from the group consisting of sexual behaviors or characteristics.

[0113] In one embodiment, the magnetic behavior or property is present at a temperature below: i) 1 0 5 , 10 3 , 500, 350, 200, 100, 50, 20, 10, 1, 0.5 or 1 K (Kelvin); ii) K iii) the melting or fusion temperature, or iv) the blocking temperature.

[0114] In some other embodiments, the magnetic behavior or properties are: i) 0.5, 1, 10, 20; exists at temperatures greater than 50, 100, 200, 350, 500, 103 or 105 K, ii) Curie temperature, iii) melting temperature, or iv) blocking temperature.

[0115] In yet some other embodiments, the magnetic behavior or properties are -20 From 10 20 K, or between 0.1 and 1000 K.

[0116] In one embodiment, magnetic resonance imaging is used, particularly to track the evolution or growth of a body part after treatment. Imaging (MRI), Computed Tomography (CT), Scanner, Positron Emission Tomography Imaging techniques such as PET, radiography, or ultrasound imaging can be used to identify body parts. It needs to be imaged.

[0117] In one embodiment of the present invention, the composition of magnetic nanoparticles, particularly magnetosomes, improves the efficiency of body parts. This prevents accurate imaging.

[0118] In some other embodiments of the present invention, the concentration of magnetic nanoparticles, particularly magnetosomes, is It is too large to allow efficient imaging of body parts.

[0119] In yet some other embodiments of the present invention, the magnetic nanoparticles, particularly magnetosomes, are Acts like a cleaner or hides body parts and prevents efficient imaging of body parts There is a possibility that.

[0120] In one embodiment of the present invention, the composition of magnetic nanoparticles, in particular magnetosomes, is used for imaging body parts. The information is adjusted or modified to allow for the

[0121] In one embodiment, the iron oxide composition is selected from the group consisting of lithium, beryllium, scandium, titanium, vanadium, Al, Cr, Mn, Fe, Ni, Cu, Zinc, B, C, N, Oxygen, Fluorine Helium, alkali metals, alkaline earth metals, hard metals, triel, tetrahydrofuran Trala, pentyl, pnictogen, chalcogen, halogen, or nobel gas family The composition is replaced by another material selected from the group consisting of:

[0122] In another embodiment of the present invention, magnetic nanoparticles, in particular magnetosomes, are used, in particular 10 -20 , 1 0 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10, 10 3 , 10 6 , 10 9 , or 10 20 Less than mg / cm 3 or mg / cm of body part 3 The concentration is reduced considerably, allowing for efficient imaging.

[0123] In yet another embodiment of the present invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is at a minimum and the maximum value.

[0124] In one embodiment of the present invention, the minimum is determined by the thermal absorption of magnetic nanoparticles, in particular magnetosomes. Generation or synthesis from magnetic nanoparticles, in particular magnetosomes, under irradiation with laser radiation The ion exchange reaction is large enough to allow dissociation of the compound.

[0125] In one embodiment of the present invention, the minimum is 1 cm 3 Hit or body part 1cm 3 10 per - 20 , 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10, 10 3 , 10 6 , 10 9 , or 10 20 Higher than mg.

[0126] In some other embodiments of the invention, the maximum value is sufficient to allow imaging of the body part. Very low.

[0127] In one embodiment of the present invention, the maximum value is 1 cm 3 Hit or body part 1cm 3 1 per 0 -20 , 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10, 10 3 , 10 6 , 10 9 , or 10 20 Larger than mg.

[0128] In one embodiment of the present invention, the SAR of magnetic nanoparticles, particularly magnetosomes, is As defined below, SAR M or SAR real It can be specified as follows.

[0129] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 in gnetosomes; It may consist of more than 30, 35 or 40 chains.

[0130] The magnetic nanoparticles, in particular magnetosomes, are preferably prepared by their extraction or from magnetotactic bacteria. After extraction or separation, they can be arranged in chains on the inside or outside of magnetotactic bacteria. can.

[0131] In one embodiment of the present invention, the magnetic nanoparticles, in particular the magnetosomes, are not arranged in chains. .

[0132] In one embodiment of the present invention, magnetic nanoparticles, particularly magnetosomes, are purified to remove endotoxins and or other biological or carbonaceous materials, such as proteins from magnetotactic bacteria and Such purification can be achieved by removing 10, 50, or 90% or more of the lipids. Detergents such as KOH can be used. Purified magnetic nanoparticles, especially magnetosomes, , carboxylic acids, phosphoric acids, sulfonic acids, esters, amides, ketones, alcohols, phenols Alkyl, thiol, amine, ether, sulfide, acid anhydride, acyl halide, amidine, aryl The group containing: amido, nitrile, hydroperoxide, imine, aldehyde, or peroxide. The coating can be recoated with a synthetic coating such as a material containing a functional group selected from The coating is made of carboxy-methyl-dextran, citric acid, phosphatidylcholine, It can be made with diethyl ester (DOPC), or oleic acid.

[0133] In one embodiment of the present invention, the coating is a magnetic nanoparticle in a matrix or solvent such as water. The present invention enables the dispersion of purified magnetic nanoparticles, particularly magnetosomes. The formulation (recoated or not) is particularly non-pyrogenic.

[0134] They are, in particular, 10 8 , 10 5 , 10 3 , or 10EU(end i) mm 3 ii) mL of magnetic nanoparticles, especially magneto 3) mL of magnetic nanoparticles, specifically magnetosomes, suspension; or iv ) mL or cm3 of body part, purified magnetic nanoparticles, especially magnetosomes (recoated The particles (whether or not treated) are resuspended in a liquid or redistributed in a matrix. The dispersion may be dispersed to provide a uniform dispersion or high stability.

[0135] In one embodiment of the present invention, the suspension of magnetic nanoparticles, in particular magnetosomes, is stable and This is particularly true for magnetic nanoparticles, particularly magnetosomes, at concentrations of 1, 5, 10, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 1000, 1000 This means it is stable at concentrations greater than 100, 200, 500, or 1000 mg. That is, the optical density of this suspension, measured in particular at 480 nm or some other fixed wavelength, is In particular, after homogenization or mixing of this suspension, 3 , 10 7 , or 10 20 seconds does not decrease by more than 1, 5, 10, 50, 75, or 90% over a period of time.

[0136] In another embodiment of the present invention, the aggregates of magnetic nanoparticles, particularly magnetosomes, are uniformly distributed. This is because magnetic nanoparticles, especially magnetosomes, Somes are 10 -6, 10 -3, 10 -1, 1, 5, 10, 50, or 75% of the volume This percentage is used to refer to the percentage of a substance that is administered, mixed, inserted, or introduced into a body. The size of the magnetic nanoparticles, particularly magnetosomes, is measured prior to administration, mixing, insertion, or introduction. The magnetic nanoparticles, particularly magnetosomes, are administered, mixed, inserted or introduced into the body. The magnetic nanoparticles, in particular magnetosomes, can be administered, mixed, inserted or embedded between the volumes of body parts. After introduction into the body parts, 10 50 , 10 20 , 10 10 , 10 5 , 10 2 , 10, or 1 minute The magnetic nanoparticles, especially magnetosomes, account for less than 10% of the total measured magnetic nanoparticles. This is the value divided by the volume of the body part.

[0137] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are at least 1, 2, 5, 1 0, 10 3 , 10 6 , or 10 9 An organism designated as a composite organism consisting of 10 eukaryotic or prokaryotic cells Thus, it is synthesized.

[0138] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are intracellular, i.e. It is synthesized inside a karyotic or prokaryotic cell.

[0139] In another embodiment of the invention, the magnetic nanoparticles, in particular magnetosomes, are administered extracellularly, i.e. It is synthesized outside of a eukaryotic or prokaryotic cell.

[0140] In yet another embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are capable of binding to living organisms, cells, A compartment, organelle, or cell that is specifically produced by a eukaryotic or prokaryotic cell, or to other biological materials such as proteins, lipids, enzymes, DNA, or RNA derived from them. Thus, they are synthesized or produced or crystallized or assembled or converted into nanoparticles.

[0141] In some other embodiments of the invention, chemical synthesis is used to create compartments, organelles, and Chemicals or compounds that mimic, copy, or replicate the functions of other biological substances. wherein the chemical synthesis or chemicals are used to prepare magnetic nanoparticles, in particular magnetosomes. It may be used in or result from the manufacture of

[0142] In one embodiment of the invention, the compartment, organelle, or other biological material is a lysosome, Endosomes, vesicles, and especially those that dissolve or convert crystallized iron to free iron or convert free iron to crystalline iron It is a biological substance that has the ability or function of being converted into ferric iron.

[0143] In one embodiment of the invention, this conversion is carried out in a partial, in particular partially crystallized, iron atom or iron Causes the destruction or formation of crystallized aggregates of atoms or ions, or in particular crystallized iron and This results in a mixture of amorphous iron.

[0144] In one embodiment of the present invention, the crystallized iron is characterized in particular by the transmission or The iron atoms or crystal faces that result in the presence of crystal faces that can be observed using techniques such as scanning electron microscopy. Free iron is defined as a collection of iron or ions, and free iron is used as a characterization method. For example, using a transmission or scanning electron microscope, this is particularly highlighted by the absence of a diffraction pattern. is defined as one of several iron atoms or ions that do not result in the existence of a crystal face. will be done.

[0145] gnetosomes, are not synthesized chemically or are different from chemical nanopa rticles. In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are synthesized by the living body. However, at that time, the crystallization of iron oxides, the stabilization of iron oxide minerals, magnetic nanoparticles, especially magneto At least one, two, five, ten or more of the mineral structures in the serosomes are organized as chains or aggregates. or 100 steps of their production, in particular by eukaryotic or prokaryotic cells. or organisms, cells, compartments, organelles, or proteins, lipids derived therefrom; They involve or result from other biological substances such as enzymes, DNA, or RNA. In the case of It may mean something different than chemical nanoparticles.

[0146] In another embodiment of the present invention, the magnetic nanoparticles are not synthesized by the living body, but rather are oxidized. Crystallization of iron, stabilization of iron oxide minerals, e.g., microstructuring of magnetic nanoparticles as chains or aggregates The manufacture of these products in less than 1, 2, 5, 10 or 100 steps, such as the organization of neural An organism, cell, compartment, organelle, or tissue produced by a eukaryotic or prokaryotic cell or involving other biological substances such as proteins, lipids, enzymes, DNA or RNA Due to them.

[0147] In this case, this means that the magnetic nanoparticles are chemically synthesized or are the same as the chemical nanoparticles. It can mean that the

[0148] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are attached to biological or prokaryotic cells. These are synthesized by bacteria, most selectively by Magnetospirillum magneoides. Netum strain AMB-1, Magnetotacticoccus strain MC-1, and three facultative anaerobic vibrio Magnetospirillum magnetotacticum strain MS-1, Magnetospirillum magnetotacticum strain MS-2, Magnetospirillum magnetotacticum strain MS-3, Magnetospirillum magnetotacticum strain MS-4, Magnetospirillum magnetotacticum strain MS-1, Magnetospirillum magnetotacticum strain MS-2, Magnetospirillum magnetotacticum strain MS-3, Magnetospirillum magnetotacticum strain MS-4 Tospirillum gryphiswaldens strain MSR-1, a facultative anaerobic magnetotactic spirillum, magnetos Pillium magneticum strain MGT-1, and the obligate anaerobe Desulfovibrio magnetotelluric acid and magnetotactic cells such as MRICAM RS-1.

[0149] In one embodiment of the present invention, magnetotactic bacteria produce magnetic nanoparticles, in particular magnetosomes. In one embodiment of the present invention, magnetotactic bacteria are defined as organisms that can They use particles, specifically magnetosomes, to swim in the direction of the Earth's magnetic field.

[0150] In one embodiment of the present invention, magnetotactic bacteria synthesize magnetic nanoparticles, in particular magnetosomes. These magnetic nanoparticles, specifically magnetosomes, are defined as bacteria that can Characterized by at least one of the following properties: i) produced intracellularly; i) They are magnetic; iii) They contain minerals, their cores being especially sensitive to metal acids such as iron oxides. v) Their core consists of biological compounds such as lipids, proteins, and endotoxins. Although surrounded by a substance, they are specifically removed, most selectively by magnetotactic agents such as those found in humans. vi) are arranged in chains; vii) are suitable for laser irradiation; It generates heat when exposed to light or laser irradiation.

[0151] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are taken up by magnetotactic bacteria. The mineral fraction formed, i.e. the crystallized iron oxide produced by these bacteria in particular, nothing.

[0152] In this case, magnetic nanoparticles, in particular magnetosomes, or magnetic nanoparticles, in particular magnetosomes The mineral portion of the syrup is produced by the proteins, lipids, and endotoxins produced by these bacteria. or having 0.1, 1, 10, 30, 50, or 75% or more carbon or carbonaceous matter Does not contain any biological material.

[0153] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are taken up by magnetotactic bacteria. The mineral part formed by the microbial growth and the carbonaceous biological material synthesized by magnetotactic bacteria were then separated. Such substances include those for medical, chemical, biological or cosmetic purposes that may be caused by laser. It can be used in particular in the treatment of immune responses against pathological cells. Therapeutic strategies include inducing a response, targeting pathological cells, or exerting a pharmacological or metabolic effect. Such substances may have therapeutic or cosmetic benefits. Magnetotaxis of proteins or other types of immunogenic or toxic proteins, lipids, DNA, RNA, etc. In some cases, such materials may be destroyed by lasers, including toxic carbonaceous materials synthesized by toxic bacteria. for or during any medical, chemical, biological or cosmetic treatment, in particular Prevent the removal of other substances that are non-toxic and / or have benefits or potential effectiveness. Such materials are selectively removed or destroyed in order to be absorbed by magnetotactic bacteria. If the material contains carbonaceous material formed by laser irradiation, it may be used for medical, chemical, biological or It can be used in cosmetic treatments, where it specifically targets or destroys diseased cells, which in turn destroys healthy cells. Such materials are particularly non-toxic to healthy cells, and such materials are particularly suitable for use as magnetic nanoparticles, in particular magnetrons. The magnetic nanoparticles are preferably maintained within or on the surface of magnetosomes, particularly magnetosomes. or, in particular, prior to administration of magnetic nanoparticles, in particular magnetosomes, to body parts, laser light Magnetic nanoparticles, particularly magnetosomes, are wrapped around or around the magnetic nanoparticles, either before or after irradiation with radiation. Binding or connecting.

[0154] In one embodiment of the invention, the substance according to the previous embodiment is a compound.

[0155] In one embodiment of the present invention, the pathological cells are old, particularly those aged 10 -9 , 10 -6 , 10 -3 , 1, 10 3 , 10 6 Cells older than minutes, or specifically 1, 5, 10, 25, 50, 75, 80, 90, or Cells belonging to centenarians or cells that have undergone apoptotic or necrotic states, or or are larger or smaller than healthy cells, especially by factors of 1.1, 1.2, 1.5, 2, 5, 10, or 103. Cells that have a smaller size, or organelles that do not function properly, or fewer enzymes than healthy cells. mitochondria that produce energy, or more or less amino acids than healthy cells ribosomes that link the ribosomes together, or by transmembrane diffusion or endosome diffusion as they normally do in healthy cells These are cells with a plasma membrane that does not allow for endocytosis.

[0156] In another embodiment of the invention, a pathological cell is a cell that results in an unsightly or abnormal appearance. Abnormal appearances are observed in 1, 5, 10, 50, or 100% of all individuals or a representative sample of the entire population. Abnormality can be defined as an appearance or condition that differs from that of 75 or 90%. A bad appearance may also be indicated by skin disorders, the presence of plaques on the skin, redness, acne, itching, or blisters. It may also be related to the presence of

[0157] In still other embodiments of the present invention, the pathological cells are cells that are involved in cancer, malfunction of body parts, Death of the whole or an individual, or high fever, or especially the loss of life within the whole or part of an individual. Increase in body temperature by 0.1, 2, 3, 4, 5, 10, 50, or 100°C above physiological temperature These are defined as the cells that are responsible for the formation of the cytoplasmic mucosa.

[0158] In still other embodiments of the present invention, the pathological cells do not divide at a normal rate. 1.1, 2, 5, 10, 10 faster than the rate at which healthy cells divide. 3 , 10 6 , or 10 9 Defined as cells that divide at a rapid rate.

[0159] In some still further embodiments of the present invention, the pathological cells are those in the body part. the presence of a large amount of, or 1 cm of, that body part 3 1, 10, 10 3 , 10 6 , 10 9 , or 10 20 is defined by the presence of more than 100 pathological cells.

[0160] In still other embodiments of the invention, the pathological cells are those that indicate that the individual is afflicted with a disease. The time before the individual is diagnosed with a disease, particularly a disease that is causing the appearance of pathological cells. Before, especially 1, 2, 10, 10 3 , 10 6 , 10 9 , or 10 40 The time period below and the individual After or during the disease, especially after the onset of the disease in that individual, 1, 2, 10, 10 3 , 10 6 , 10 9 , or 10 40 Between hours and times after hours, especially 1.1, 10, 10 3 , 10 6 , 10 9 , or 10 20 It is defined as an increase by a factor exceeding

[0161] In one embodiment of the invention, the pathological cells are bacteria, in particular pathological bacteria, tumor cells, in particular benign Or malignant tumor cells.

[0162] In one embodiment of the present invention, the pathological cells are in contact with a foreign substance that does not belong to the individual, such as a virus. Defined as cells that are in contact and interacting with each other.

[0163] In one embodiment of the present invention, the pathological cell is a cell in which a virus has invaded or is replicating. It is defined as a cell.

[0164] In one embodiment of the present invention, the pathological cells are specifically targeted to the proliferation, reproduction, survival and / or proliferation of the cells themselves. They either form colonies or attack cells to allow for either death or Viruses or other organisms that destroy or use cells or enter into interaction with cells is assimilated into the object.

[0165] In one embodiment of the present invention, a pathological cell is a healthy cell that has undergone transformation, modification, or is specifically defined as healthy cells that have died due to

[0166] In one embodiment of the present invention, the cells are colonized, used, or interacted with. The presence of a virus or other organism or entity entering the body may be related to the presence of pathological cells in the body parts. The present invention may be used to infer the presence or absence of pathological cells in a body part.

[0167] In one embodiment of the present invention, the magnetic nanoparticles are chemical nanoparticles, i.e., synthesized by synthetic biology, and most Although not specifically synthesized by magnetotactic bacteria, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 common features, where these common features are The properties are particularly ferrimagnetic behavior, large size, crystallization, monodomain, maghemite, etc. or magnetite composition, chain arrangement, cubes, spheres, cuboctahedrons, cigars, or elongated A geometric shape, or ratio between the two different dimensions of the magnetosome, is 10 -3 -10 3 It is.

[0168] In one embodiment of the present invention, the magnetic nanoparticles are superparamagnetic or ferrimagnetic nanoparticles. The magnetic properties of the magnetic nanoparticles were obtained, particularly at 0.1, 1, 5, 10, 50, 100, 200, 3 00, or at temperatures above 400K.

[0169] In one embodiment of the present invention, the magnetic nanoparticles are made of metal or metal oxide, or mostly gold. It includes or comprises group atoms, or metal atoms and oxygen atoms.

[0170] In some other embodiments of the present invention, the magnetic nanoparticles are maghemite or magnetite. The term includes or contains iron oxides such as iron oxides.

[0171] In one embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are duration of the top, maximum or minimum temperature or magnetic nanoparticles, especially magnetosomes, is at least the maximum or minimum rate of dissociation resulting from sequential irradiation of body parts with laser radiation. Both are defined by a single characteristic.

[0172] In one embodiment of the invention, the irradiation of magnetosomes with a laser or laser radiation comprises: It can mean that the magnetosomes are illuminated by laser irradiation.

[0173] In one embodiment of the present invention, the irradiation by laser radiation is or is based on electromagnetic waves. The laser radiation may be an electromagnetic wave. The electromagnetic wave or laser radiation may be, in particular, a laser. Emitted or generated by equipment or devices. Electromagnetic waves are particularly relevant for: i) the propagation of electric and magnetic waves; ii) waves that do not involve the movement of particles with mass; and iii) waves containing photons, or iv) light waves. In particular, the magnetic field generated by such electromagnetic waves. is 10 10 , 10 5 , 10 2 , 10, 1, 10 -1 , 10 -2 , 10 -5 , or 10 -10 Has a strength lower than T The electric field generated by that electromagnetic field is 10 10 , 10 5 , 10 2 , 10, 1, 10 -1 , 10 -2 , 10-5 , or 10 -10 Vm -1 has a strength of less than

[0174] In one embodiment of the present invention, the electromagnetic wave is 10 10 , 10 5 , 10 3 , 10, 1, 10 -1 , 10 -3 , 10 -5 , or 10 -10 Spatial or temporal at frequencies below GHz It vibrates.

[0175] In some other embodiments of the present invention, the electromagnetic waves are 10 , 10 5 , 10 3 , 10, 1 , 10 -1 , 10 -3 , 10 -5 , or 10 -10 At frequencies above GHz, Vibrates in time.

[0176] In one embodiment of the present invention, the laser radiation is monochromatic, i.e., it contains photons of a single wavelength.

[0177] In some other embodiments of the invention, the laser radiation is polychromatic, i.e. it has multiple or 1, 2, 5, 10 or 10 3 Photons with wavelengths exceeding include.

[0178] In one embodiment of the present invention, the laser device is referred to as a laser.

[0179] In one embodiment of the present invention, the laser device is a process for light amplification, in particular based on stimulated emission of electromagnetic radiation. Laser radiation is a device that emits or generates laser radiation through a process, in particular In conjunction with or for use in conjunction with: i) the transmission of laser light from this device to any body part; ii) a system, such as an optical fiber, capable of carrying or transporting laser radiation; Such systems, especially those that converge or diverge or that direct a laser beam at a body part or To specifically focus or defocus or defocus on a particular location of a body part In this patent application, a combination of a laser instrument and a lens capable of light transport and / or focusing is described. The combination or association of the system is called a laser device, or a laser or laser The laser instruments or devices are in particular: a) gas lasers, in particular helium neon , argon, krypton, xenon ions, nitrogen, carbon dioxide or monoxide, or ethylene ii) chemical lasers, in particular hydrogen fluoride, deuterium fluoride, chemical oxygen - iodine or total vapor iodine laser, or iii) dye laser, or iv) metal vapor laser. Lasers, especially helium-cadmium, helium-mercury, helium-selenium, -silver, strontium vapor, neon copper, copper vapor, gold vapor, or manganese vapor laser or v) solid-state lasers, in particular ruby, Nd:YAG, NdCrYAG, Er: YAG, Neodymium YLP, Neodymium doped yttrium orthovanaate, Neodymium doped Yttrium calcium oxoborate, neodymium glass, titanium sapphire, Lithium YAG, Ytterbium YAG, Ytterbium: 2 O 3 , Ytterbium-doped glass , Holmium YAG, or cerium doped lithium strontium (or calcium Fluoride aluminum, promethium-147 doped phosphate glass, chromium doped chrysoberyl (Alexandrite), Erbium-doped and Erbium-Ytterbium co-doped glass Calcium fluoride with trivalent uranium or calcium fluoride with divalent samarium v) semiconductor lasers, in particular semiconductor diodes, GaN, InGaN, A lGaInP, AlGaAs, InGaAsP, lead salt, vertical cavity surface emitting, quantum cascade , or hybrid silicon lasers, or vi) free electron, gas dynamic, "Nickel-like" samarium, Raman, or nuclear pumped lasers. Laser devices include, in particular: They operate in one of the following different wavelength ranges: X-ray, ultraviolet, visible light, near infrared, mid-red External rays, far infrared rays.

[0180] In one embodiment of the present invention, the continuous wave laser output is 10 -3 mW to 10 3 Included between kW It is possible.

[0181] In another embodiment of the invention, the laser pulse energy is especially comprised between 1 mJ and 1 kJ. Can be enjoyed.

[0182] In one embodiment of the present invention, the laser is monomodal.

[0183] In another embodiment of the invention, the laser is multi-modal.

[0184] In one embodiment of the present invention, the wavelength λ is monochromatic laser radiation. Or the distribution Δλ is 10 3 λ, 10λ, λ / 1.01, λ / 2, λ / 10, λ / 10 3 It is especially important that This is a sign.

[0185] In another embodiment of the present invention, n different wavelengths λi(1 <i <n)の Each is characterized by a spread or distribution in wavelength, which is the sum of Δλi and (λi-λ j), where λi and λj are the two wavelengths of the polychromatic laser light. At different wavelengths, especially 10 9 , 10 6 , 10 3 , 10, or 10 -1 nm shorter.

[0186] In one embodiment of the present invention, the laser radiation is measured using a laser power, a laser power density, a laser intensity, Characterized by, having, or relating to a laser wavelength, or , including them.

[0187] In one embodiment of the present invention, the laser emission is continuous.

[0188] In some other embodiments of the invention, the laser light is pulsed.

[0189] In one embodiment of the present invention, the duration of the pulses is 10, 1, 10 -1 , 10 -3 , 10 -6 , 10 -9 or 10 -15 It is less than a second, particularly less than 10 seconds, and more preferably less than 1 second.

[0190] In some other embodiments of the present invention, the duration of the pulse is 10 -50 , 10 -20 , 10 -10 , 10 -5 , 10 -1 or longer than 1 second, preferably 10 -50 More than a second , more preferably 10 -20 Longer than seconds.

[0191] In one embodiment of the present invention, the term laser radiation is understood to mean a laser, a laser device, a laser laser device, laser radiation beam, laser beam, laser energy, laser intensity, laser Laser power, laser power density, laser intensity, laser frequency, laser wavelength or laser It can refer to or mean laser pulsation.

[0192] In still other embodiments of the present invention, the laser power density is determined by controlling the laser power, particularly the body part to which the laser radiation is applied or to which the laser radiation is specifically applied It can be defined as a product, a surface, or a division by a length.

[0193] In one embodiment of the present invention, the laser power or laser power density or other parameters of the laser are The laser may be used outside or at some distance from the equipment or device that generates the laser radiation, particularly at -20 , 10 -10 , 10 -5 , 1, 10 5 , 10 10 , or 10 20 Higher than nm The laser power or power density or other parameter of the laser measured over distance.

[0194] In one embodiment of the present invention, the laser power or laser power density or other power of the laser is The parameters are measured in particular in body parts or regions of magnetic nanoparticles, particularly magnetosomes. will be done.

[0195] In one embodiment of the present invention, the laser radiation is, in particular, 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10 3 , or 10 6 T higher than the intensity, especially 10 -9 , 10 -6 , 10 -3 , 1 0 -1 , 1, 10 kHz or higher frequencies, sonic, ultrasonic, X-ray, gamma ray, or has a mass other than 0, or 10 -80 , 10 -40 , 10 -20 , 10 -10 , 10 -5 , 10 -1 or of particles having a mass of more than 1 gram, especially in terms of space or time A wave, magnetic, alternating magnetic field relating to, inducing, or containing interfacial movement or vibration No, it is different from them.

[0196] In one embodiment of the present invention, the medical, chemical, biological or cosmetic effects of laser radiation are medical, chemical, biological or cosmetic treatment, therapy or rehabilitation Laser radiation, which may be designated as laser therapy, is used in particular for medical, pharmaceutical and immunological purposes. for the purpose of producing a metabolic, diagnostic, medical device, drug, biological, or cosmetic effect. For this purpose, magnetic nanoparticles, in particular magnetosomes, or laser radiation irradiated on body parts or or irradiation by laser radiation.

[0197] In one embodiment of the invention, the medical treatment is the treatment of a disease or disorder, such as an infection, cancer, or the like. Or it can be a therapeutic procedure, which is the treatment of illnesses caused by the malfunction of an organ or part of the body. It may be the destruction or disappearance of pathological cells, especially 1, 5, 10, 50, 75, may result in or be associated with greater than 80 or 90% destruction or loss. is a disease that occurs especially in body parts after medical, chemical, biological or cosmetic treatment. The ratio of the number of pathological cells to the number of pathological cells present in a particular body part before the medical treatment. The presence of pathological cells, especially in a body part, can lead to the malfunction of the body part of an individual. This may be the cause.

[0198] In one embodiment of the present invention, the medical or chemical or biological or cosmetic treatment is a treatment for a disease. The diagnosis or cosmetic treatment of

[0199] In one embodiment of the present invention, a medical, chemical, biological or cosmetic treatment using a laser is provided. The targeted treatment is aimed at preventing the presence of viruses, bacteria, or other types of organisms or pathological cells. The present invention relates to the treatment of diseases, particularly infectious diseases, caused by or associated with the initiation of disease in an individual or Present in treated individuals prior to emergence.

[0200] In one embodiment of the present invention, the medical or chemical or biological or cosmetic treatment is anemia. anemia or lack of a substance in a body part, especially anemia or iron or its compounds It is a treatment for a lack of the substance it contains.

[0201] In one embodiment of the present invention, anemia is defined as the concentration of a substance in an individual, which is In individuals suffering from anemia, the mean mean scores were 1.001, 1.01, 1.1, 2, 5, 1.0% compared to healthy individuals. 10, 10 2 , 10 5 , 10 10 , or 10 20 More than twice as low.

[0202] In one embodiment, the anemia of substances contained in the body parts is mediated by magnetic nanoparticles, in particular magnetosomes. As the concentration of a substance or compound, such as iron, oxygen, or a substance contained in a compound It is defined that before administration of magnetic nanoparticles, in particular magnetosomes, in that body part, or without magnetic nanoparticles, particularly magnetosomes, in the body parts, particularly magnetic nanoparticles after administration of the drug, particularly magnetosomes, or in the presence of magnetic nanoparticles, particularly magnetosomes In particular, lower than 1.001, 1.01, 1.1, 2, 5, 10, 10 2 , 10 5 , 10 10 , or 10 20 Twice lower.

[0203] In one embodiment of the present invention, certain compounds are used in the laser, particularly in magnetic nanoparticles, particularly magnetosomes. Prior to irradiation with radiation, the magnetic nanoparticles, in particular magnetosomes, are bound or attached.

[0204] In one embodiment of the invention, the compound or its compounds are 2 , 10 3 , 10 5 , 10 10 , 10 20 , or 10 50 Characterized by an ensemble containing more than can be done.

[0205] In yet another embodiment of the present invention, the compound or compounds thereof may be 1, 10, 10 2 , 1 0 3 , 10 5 , 10 10 , 10 20 , or 10 50 By assemblages containing compounds less than Can be characterized.

[0206] In one embodiment of the present invention, the laser radiation is directed in particular from magnetic nanoparticles, in particular from magnetosomes. Pertaining to or related to the movement, vibration, or oscillation of a compound following dissociation of that compound from To relate to, induce, produce, result from, or cause , and it is the radiation that produces them.

[0207] In one embodiment of the invention, the compound is a therapeutic, immunogenic, metabolic, luminescent, fluorescent, radioactive, are therapeutic, immunogenic, metabolic, or chemical compounds, A compound that produces a luminescent, fluorescent, radioactive, diagnostic effect.

[0208] In one embodiment of the present invention, the compound is part of a magnetic nanoparticle, in particular a magnetosome. In this case, it may be free iron or free oxygen, especially in ionic form, which is especially suitable for use as a magnetic nanoparticle. Magnetosomes are particles that are dissociated, leaked or diffused from magnetosomes, particularly magnetosomes. or under irradiation of body parts with laser radiation. After dissolution of the magnetic nanoparticles, in particular magnetosomes, after administration of biocompatible nanoparticles, particularly magnetosomes, to body parts.

[0209] In one embodiment of the present invention, magnetic nanoparticles, particularly magnetosomes, are used to direct their application to body parts. When administered in contact with or near a body part, it may be dangerous to -1 , 10 -2 , 10 -3 , 10 -4 , 10 -5 , 10 -6 , or 10 -9 The body parts are administered less than a metre apart. In this case, magnetic nanoparticles, especially magnetosomes, are transported from the area where they were administered to the body part. It may not be necessary to transmit or disseminate the

[0210] In another embodiment of the invention, the magnetic nanoparticles, in particular magnetosomes, are capable of detecting their location from body parts. When administered in excess of 10-1, 10-2, or 10-, the body 3, 10-4, 10-5, 10-6, or 10-9 m from the body part. In this case, the magnetic nanoparticles, especially magnetosomes, are located in the area where they are administered. can be transported or diffused from the body to body parts.

[0211] In another embodiment of the invention, the magnetic nanoparticles, in particular magnetosomes, are characterized in that they are attached to body parts. When injected into, mixed with, introduced into, or inserted into It is sometimes administered to body parts.

[0212] In another embodiment of the invention, the magnetic nanoparticles, in particular magnetosomes, are or 10% of that body part when administered into the body -9 , 10 -7 , 10 -5 , 10 -3 , More than 1, 10, 25, 50, or 75% of the magnetic nanoparticles in the body parts. , in particular the volume of the area occupied by magnetosomes and, in particular, magnetic nanoparticles, in particular magnetosomes. This occupancy can be the ratio between the volume of the body part that consists of the area that does not contain the tosomes. After administration of magnetic nanoparticles, especially magnetosomes, 10 -5 , 10 - 3, 10 -1 , 1, 10, 10 3 , or 10 5 corresponds to that measured in minutes.

[0213] In one embodiment of the present invention, magnetic nanoparticles, in particular magnetosomes, are used in body parts. The volume of the occupied area is designated as the area of ​​the magnetic nanoparticle, in particular the magnetosome. The magnetic nanoparticles, particularly magnetosomes, are preferably used in body parts to deliver magnetic nanoparticles, particularly magnetosomes, to the body. The volume occupied by the aggregate of netosomes may be a volume occupied by the aggregate of magnetic nanoparticles, particularly magnetosomes. M is 10 9 , 10 6 , 10 3 , or less than 10 nm apart.

[0214] In one embodiment of the present invention, magnetic nanoparticles, particularly magnetic nanoparticles within assemblies of magnetosomes, are The separation distance between particles, especially magnetosomes, is related to the magnetic nanoparticles in this assembly, especially the magnetosomes. It can correspond to the average or maximum distance separating the netosomes.

[0215] In one embodiment of the present invention, the distribution of distances separating magnetosomes is determined by the magnetic nanoparticles. In particular, magnetosomes are a minority group of solids, i.e. magnetic nanoparticles. The total number of particles, especially magnetosomes, is 50, 10, 1, 10 -2 or 10 -5 Less than % of It can be emphasized that the small separation distance, i.e., 10 9 , 10 6 , 10 3 ,or Separation distances smaller than 10 nm or larger, i.e., especially 10 9 , 10 6 , 10 3 , or a separation distance greater than 10 nm. The presence of nanoparticles, especially magnetosomes, in small numbers indicates that magnetic nanoparticles, especially magnetosomes, No special consideration is taken into account for estimating the average or maximum separation distance between the somes.

[0216] In another embodiment of the present invention, the magnetic nanoparticles, in particular magnetosomes, are administered via the following routes of administration: administered to that body part according to at least one of the following routes: topical, enteral, digestive. duct, parenteral, topical, oral, inhalation, intramuscular, subcutaneous, intratumor, intraorgan, intravenous, intraarterial, blood Within, or within an organization.

[0217] In one embodiment of the invention, the body part or part of the body part is a pathological site. A biological site is a site that is unhealthy or in a state different from that of a healthy individual, or It can be defined as the site of an unhealthy individual. It is a pathological cell, e.g., a tumor cell. may include cells, bacteria, eukaryotic or prokaryotic cells, viruses or other pathological agents. It also has been shown to be effective in detecting pathological cells, particularly in healthy individuals, and most particularly in pathological sites. Healthy cells that are not arranged or functioning as they normally would for existence It may contain more pathological cells than healthy cells. It may contain more pathological cells than healthy cells. and the number of healthy cells, which can be specifically determined by the ratio of 2, 5, 10, 10 3 , 10 6 , 10 9 , 10 20 , or 10 50 Higher.

[0218] In one embodiment of the invention, the pathological cell or the pathological cell is 1, 10, 10 2 , 10 3 , 10 5 , 10 10 , 10 20 , or 10 50 Contains more than 100 pathological cells It can be characterized by aggregation.

[0219] In one embodiment of the invention, the body part is in particular a region of magnetic nanoparticles, magnetosomes. Also designated magnetic nanoparticles, in particular magnetosomes, are included in a body part, and magnetic nanoparticles are included in a body part. , in particular free of magnetosomes, in particular outside the region of magnetic nanoparticles, in particular magnetosomes. and portions of the body part designated as body part regions.

[0220] In one embodiment of the invention, the part of the body containing the magnetic nanoparticles, in particular magnetosomes, is 10 of the energy or power of the laser -9 , 10 -7 , 10 -5 , 10 -3 , 10 -1 , 1, 5. , 10, 25, 50, 75, or more than 80% can be absorbed. However, parts of the body that do not contain magnetic nanoparticles, especially magnetosomes, are particularly vulnerable to laser irradiation. 10 for Energy or Power -9 , 10 -7 , 10 -5 , 10 -3 , 10 -1 , 1, 5 , less than 10, 25, 50, 75, or 80% can be absorbed.

[0221] In one embodiment of the invention, the part of the body containing the magnetic nanoparticles, in particular magnetosomes, is 10 of the energy or power of the laser -9 , 10 -7 , 10 -5 , 10 -3 , 10 -1 , 1, 5. , 10, 25, 50, 75, or 80% less can be absorbed. However, body parts that do not contain magnetic nanoparticles, especially magnetosomes, are particularly susceptible to laser interference. 10 of energy or power -9 , 10 -7 , 10 -5 , 10 -3 , 10 -1 , 1, 5, It can absorb 10, 25, 50, 75, or 80% or more of the amount.

[0222] In one embodiment of the present invention, this percentage is absorbed by magnetic nanoparticles, in particular magnetosomes. The energy or power of the collected laser radiation is transferred by a laser device or laser apparatus. It is expressed as the energy or power of the laser radiation produced.

[0223] In some other embodiments of the present invention, this percentage is made up of magnetic nanoparticles, particularly magnetospheric nanoparticles. The energy or power of laser radiation absorbed by a part of a body part, including a laser, is and a portion of a body part having magnetic nanoparticles, particularly magnetosomes, in The rays absorbed by both the parts of the body that contain gnetosomes and the parts of the body that do not contain gnetosomes. It represents the ratio of the amount of radiation emitted by the laser divided by the energy or power of the radiation.

[0224] In one embodiment of the invention, the body part is a body part containing a pathological site or a pathological cell. and body parts that do not contain pathological sites or pathological cells.

[0225] In one embodiment of the present invention, a body part refers to a portion of a body part.

[0226] In one embodiment of the invention, the body part portion is: i) loaded with magnetic nanoparticles, in particular magnetosomes; ii) a region of magnetic nanoparticles, in particular a region of magnetosomes, or iii ) a part of a body that contains diseased cells or a pathological site.

[0227] In some other embodiments of the invention, the portion of the body part is provided with: i) magnetic nanoparticles, in particular magnetic ii) a region outside the region of the magnetic nanoparticles. In particular, magnetosomes, or iii) pathological cells or pathological sites. Part of a body that cannot be moved.

[0228] In the present invention, the body parts or magnetic nanoparticles, in particular magnetosomes, are exposed to laser light. Exposed to or irradiated by laser radiation means that the laser beam is projected, covered, or to target, be present at, be applied in or on, or to a body part or magnetic field At least 10 of nanoparticles, especially magnetosomes -9 , 10 -7 , 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 25 , 50, 75, or 80%. This percentage can refer to the magnetic nanoparticles, in particular Magnetosomes, or magnetic nanoparticles, particularly magnetosome regions, or laser light The number or volume of areas of the body part exposed to the laser beam or irradiated with the laser beam is counted. - Magnetic nanoparticles, both exposed and unexposed to radiation, in particular magnetos The area of ​​the magnetic nanoparticles, especially magnetosomes, or the total number or volume of the body parts It represents what has happened.

[0229] In one embodiment of the present invention, the laser radiation is induced to induce toxicity to healthy cells. When the power or energy is low enough that it does not emit radiation, the body parts, or magnetic nano Covering a particle, in particular a magnetosome, or a region of a magnetic nanoparticle, in particular a magnetosome, capable of being targeted, present, applied in or on, or located outside .

[0230] In one embodiment of the present invention, healthy cells or the healthy cells are 1, 10, 102 , 10 3 , 10 5 , 10 10 , 10 20 , or 10 50 The results were characterized by aggregates containing more than 10 healthy cells. Cut.

[0231] Furthermore, in one embodiment, the body part or magnetic nanoparticles, particularly magnetosomes, or magnetic The region of the magnetic nanoparticles, particularly magnetosomes, is i) a body part, or ii) a magnetic nanoparticle, particularly a magnetosome. magnetosomes, or iii) magnetic nanoparticles, specifically laser-targeting specific magnetosome regions. When irradiation is applied or when a laser is applied, it is exposed to laser light; Or it can be illuminated by laser radiation.

[0232] In some other embodiments of the present invention, the body parts or magnetic nanoparticles, particularly magnetospheric The regions of the nanoparticles, or magnetic nanoparticles, particularly magnetosomes, can be exposed to laser radiation. The magnetic nanoparticles, especially the magnetic nanoparticles, can then be attached to the body parts or exposed to radiation. The netosomes, or the regions of the magnetic nanoparticles, particularly the magnetosomes, are illuminated or lasered. Laser radiation is applied to, or is affected by, or is produced by, laser radiation. The project is subject to repeated interference.

[0233] In one embodiment of the invention, the body part is identified by 1, 2, 5, 10, or more than 100 similar or or a different living organism, device, organ, tissue, cell, or biomolecule. As defined in this patent application, the head, neck, shoulders, arms, legs, knees, feet, hands, ankles, elbows, trunk, , a sub-member, or all or a portion of a super-member.

[0234] In one embodiment of the present invention, the body part is synthesized by water, excipients, solutions, suspensions, biological tissues. or at least one chemical element, organic material, or gel that can be produced. Includes these.

[0235] In one embodiment of the present invention, the organ or body part is a part of the musculoskeletal system, the muscular system, the digestive system, the respiratory system, , Urinary System, Female Reproductive System, Male Reproductive System, Circulatory System, Cardiovascular System, Endocrine System, Circulatory System, Lymphatic System, Nervous system (peripheral or non-peripheral) Ventricular, enteric nervous system, sensory system, integumentary system, reproductive organs (visceral or An organ or body part is an organ that is part of the human body, such as the human skeleton, Joints, ligaments, tendons, mouth, teeth, tongue, salivary glands, parotid glands, submandibular 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, ovaries, fallopian tubes, uterus, vagina, vulva, clitoris, Clitoris testis, epididymis, vas deferens, seminal vesicles, prostate, urethral tubercle, penis, scrotum, pituitary gland, pineal gland, Thyroid gland, parathyroid gland, adrenal gland, pancreas, heart, arteries, veins, capillaries, lymphatic vessels, lymph nodes, bone marrow , thymus, spleen, gut-associated lymphoid tissue, tonsils, brain, cerebrum, cerebral hemispheres, diencephalon, brain stem, midbrain, Pon, medulla oblongata, oblongata, cerebellum, spinal cord, choroid plexus, nerve, cranial nerve, spinal nerve, ganglion, Eye, cornea, iris, ciliary body, lens, retina, ear, outer ear, earlobe, middle ear, ossicles, inner ear, cochlea, Being or belonging to the vestibule of the ear, the semicircular canals, the olfactory epithelium, the tongue, the taste buds, the mammary glands, or the skin A body part or organ may belong to the circulatory system.

[0236] In one embodiment of the present invention, the body part refers to a body part of an individual.

[0237] In one embodiment of the invention, the individual is a living organism, in particular a living organism, a plant, a tree, a flour, a fungus, a mushroom, Archaea, Microorganisms, Animals, Mammals, Birds, Crustaceans, Fish, Vertebrates, Bacteria, Humans, Males In one embodiment of the present invention, the individual is specifically referred to as a treated individual. Between an individual being treated for a disease and the individual or organism that is the cause of the disease in the treated individual. A distinction is made.

[0238] In one embodiment of the invention, the individual may be living.

[0239] In some other embodiments of the invention, the individual is dead or inactivated or killed. It could be a non-life threatening organism.

[0240] In one embodiment, the body part of the individual is specifically comprised in the body part, extracted from the body part. A collection of cells, especially one, issued from or resulting from a body part , 10, 10 3 , 10 6 , 10 9 , or 10 20 It is an aggregate of more than one cell. In embodiments, these cells are cultured in a specific number, particularly 1, 10, 10 3 , 10 6 , 10 9 ,Also is 10 20 The cells can be cultured and amplified to reach the above number.

[0241] In one embodiment of the present invention, the magnetic nanoparticles according to the invention, in particular magnetosomes, are used as a drug, a medicine, Medical devices, cosmetics, biological products, products used for research purposes, or biological or chemical products It is a product used to determine the properties of biological samples.

[0242] In one embodiment of the present invention, the compound is converted into magnetic nanoparticles, in particular under irradiation by laser irradiation. The nucleosomes may be dissociated or may be dissociated from the nucleosomes, in particular magnetosomes.

[0243] In one embodiment of the invention, the compound dissociates from the magnetic nanoparticles, in particular magnetosomes, At that time, compound 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 25, 50, 75, 85 or more than 90% dissociate from the magnetic nanoparticles, especially magnetosomes, and this percentage represents the percentage of dissociation.

[0244] In one embodiment of the invention, the percentage of dissociation is determined after or under irradiation with laser radiation. The amount of compounds dissociated from magnetic nanoparticles, especially magnetosomes, and the amount of compounds irradiated by laser irradiation of compounds bound or associated with magnetic nanoparticles, particularly magnetosomes, with or without irradiation. It expresses a ratio to a quantity.

[0245] In one embodiment of the present invention, a magnetic nanoparticle, in particular a magnetosome, is bound or attached thereto. The number of compounds that were added was 1, 2, 5, 10, 10 3 , 10 5 , or 10 10 More There is a saying.

[0246] In some other embodiments of the present invention, a magnetic nanoparticle, in particular a magnetosome, The number of compounds bound or wrapped around each other is 2, 5, 10, 10 3 , 10 5 , or 10 10 Yo Less.

[0247] In still other embodiments of the present invention, the proportion of dissociated compound is determined by the laser radiation. At least 1.01, 1.1, 2, 5, 7, 10, and 10 before and after irradiation with 2 , or 10 5 It may increase by twofold.

[0248] In one embodiment of the invention, the compound is magnetic, especially in the absence of irradiation by laser radiation. They cannot or do not dissociate from nanoparticles, particularly magnetosomes. If the compound does not dissociate from the magnetic nanoparticles, particularly magnetosomes, the compound - 5 , 10 -3 , 10 -1 , 1, 5, 10, 25, 50, 75, 85, or less than 90% Dissociated from magnetic nanoparticles, particularly magnetosomes.

[0249] In one embodiment of the present invention, the compound is delivered by magnetic nanoparticles, particularly magnetosomes. 0 9 , 10 5 , 10 3 , 10, or 1 nm away, or attached to magnetic particles, particularly magnetosomes, or to magnetic nanoparticles, particularly magnetosomes. Alternatively, the compound is, in one embodiment, a magnetic nanoparticle. The children, especially the magnetosomes and their compounds, are attracted together by magnetic forces. or in particular, an intensity per unit distance of 10 -9 , 10 -6 , 10 -3 , 10 -1 , or 1T / m or T When magnetic field gradients higher than 100 kV / cm or 100 T / mm are applied, both or together, the compound is capable of binding or associating with a magnetic nanoparticle, in particular a magnetosome, or Magnetic nanoparticles, particularly magnetosomes, may not be dissociated from the magnetic nanoparticles. In particular, magnetosomes are bound or associated with magnetic nanoparticles, in particular magnetosomes. The kinetic rates of compounds that have not dissociated from the azide complex are particularly high at 10 -9 , 10 -6 , 10 -3 , 1 0 -1 , 1, 10, or 10 3 nm / sec or nm / min or nm / hr or nm / day or faster than m / seconds or m / minutes or m / hours or m / days.

[0250] In one embodiment of the present invention, the compound is delivered from magnetic nanoparticles, particularly magnetosomes. 9 , 10 5 , 10 3 , 10, or even 1 nm apart, magnetic nanoparticles, especially magneto Magnetic nanoparticles, especially magnetosomes, are not bound or associated with magnetosomes. Alternatively, in one embodiment, the compound is not attracted to a magnet. or strength per unit length is 10 -9 , 10 -6 , 10 -3 , 10 -1 , or 1T Able to move under magnetic field gradients greater than 1 / m or T / cm or T / mm. If the compound does not bind or associate with the magnetic nanoparticle, particularly the magnetosome, or may dissociate from magnetic nanoparticles, particularly magnetosomes, where the The speed of the compound is especially fast at 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10, or 1 0 3 nm / sec or nm / min or nm / hr or nm / day or m / sec or m / min or m / hr or m / day, or slower, or the kinetic rate of the compound is , 1.001, 1.01, 1.1, 2, 5, 10, 10 3 , 106, 10 9 , 10 15 , or 10 20 The motion speed or magnetic field of magnetic nanoparticles, especially magnetosomes, increases by a factor exceeding It is slower than the rate of movement of the compound bound or attached to the nanoparticles, especially magnetosomes.

[0251] In one embodiment of the invention, the percentage of dissociation is between 10 -20 % and 10 20 %, or between 10 -10 % and 10 10 %, or between 10 -5 % and 10 5 %, or better en 10 -3 % and 10 3 %, or between 10 -1 % and 10%. A percentage of dissociation higher than 100% can in one embodiment be reached, for example when a compound that di ssociates from the magnetic nanoparticle, in particular magnetosome, transforms itself or results in several compounds. In one embodiment of the present invention, the rate of dissociation is 10 -20 %-10 20 %, or 10 - 10%-10 10 %, or 10 -5 %-10 5 %, or 10 -3 %-10 3 %, Ma or 10 -1 % to 10%. In one embodiment, for example, magnetic nanoparticles, particularly magnetos When a compound dissociates from a group, it transforms itself or becomes several compounds. , a percentage of dissociation of more than 100% can be reached.

[0252] In yet another embodiment of the present invention, the irradiation with laser radiation is carried out by means of magnetic nanoparticles, in particular magnets. magnetosomes, or magnetic nanoparticles, especially magnetosomes, in the region or in the body part This refers to exposure to laser radiation.

[0253] In one embodiment of the present invention, irradiation with laser radiation is performed by the application of magnetic nanoparticles, in particular magnetosomes. Exposure of the body parts, or areas containing magnetic nanoparticles, especially magnetosomes, to laser radiation Point.

[0254] In another embodiment of the invention, the magnetic nanoparticles are in particular bound to a single magnetic nanoparticle, in particular a magnetosome. The mass, number, or weight of the compound to be mixed with the mass of a single magnetic nanoparticle, particularly a magnetosome, The ratio of numbers or weights is 10 20 , 10 9 , 10 5 , 10 2 , 2, 1, 10 -2 , 10 -5 , 10 -9 , or 10 -20 Lower.

[0255] In another embodiment of the invention, the magnetic nanoparticles are specifically bound to a single magnetic nanoparticle, in particular a magnetosome. The mass, number or weight of the compounds and the quality of the single magnetic nanoparticles, particularly magnetosomes, The ratio of quantity, number, or weight is 10 20 , 10 9 , 10 5 , 10 2 , 1, 10 -2 , 10 -5 , 10 -9 , or 10 -20 Higher.

[0256] In one embodiment of the present invention, compounds that specifically bind to single magnetic nanoparticles, particularly magnetosomes, The appropriate range of values ​​for the number is between 1 and 178, where the minimum value of 1 is the number of The maximum number of compounds that can be linked to a tosome is 178, as described in Patent Document 1. The number of RhB molecules linked to a single magnetosome, which is at least partially In one embodiment, the maximum The value 178 is specifically 5, 10, 10 3 , 10 7 , 10 10 ,Also is 10 20 i) magnetic nanoparticles, especially magneto The size or mass of the compound bound to the serosome is determined, particularly at 1.1, 2, 5, 10, 10 3 , 10 7 , 10 10 , or 10 20 ii) reduce the compound by a factor of more than or iii) modify the type of binding between magnetic nanoparticles, particularly magnetosomes, or Modify the way things are attached or attached to magnetic nanoparticles, particularly magnetosomes.

[0257] In one embodiment of the present invention, the magnetic nanoparticles or body parts are first lasered in a first step. This is particularly true for body parts, in particular magnetic nanoparticles, in particular magnetosomes. Any part of the body, including the skin, that receives or absorbs the energy or power of the laser. or in particular of laser radiation emitted or generated by a laser instrument or device. At least 10% of energy or power -9 , 10 -7 , 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 25, 50, 75, or 80% of This means that the magnetic nanoparticles, especially magnetosomes, are absorbed by some of the body parts that contain them. The energy or power of a laser can be destructive to body parts that do not contain magnetic nanoparticles, especially magnetic It can be absorbed by the sphingosome.

[0258] In one embodiment of the present invention, the first step means during the first step or etc. It can be valuable.

[0259] The first step is in particular to determine whether the body part or the magnetic nanoparticles, in particular magnetosomes, are in particular 0 Watts or body parts cm 3 Watts per gram or higher than watts per gram of nanoparticles During or during the step of being irradiated with laser radiation at a low laser power. Alternatively, the first step is to introduce magnetic particles into the body parts or into the magnetic nanoparticles, in particular magnetosomes, and the second step is to introduce magnetic particles into the body parts or into the magnetic nanoparticles, in particular magnetosomes. More than the laser power in steps, especially at least 0, 1.1, 1.5, 5, 10, 10 3 、 10 5 or 10 10 During or during the step of irradiating with high power radiation at multiples of It is.

[0260] In one embodiment, in particular in the first step, and possibly also in the second step, the laser output The force is generated by the magnetic nanoparticles, in particular magnetosomes, the regions of the magnetic nanoparticles, in particular magnetosomes, Magnetic nanoparticles, especially magnetosomes, can cause an increase in temperature in some body parts. and in particular of body parts which do not contain magnetic nanoparticles, in particular magnetosomes. It is set to prevent the temperature from rising.

[0261] In one embodiment of the present invention, "in the second step" means during the second step. or equivalent.

[0262] In one embodiment of the present invention, in particular in the first step, and possibly also in the second step, Laser power or laser power density is increased by 10 9 , 10 6 , 10 3 , 10 2 , 10, or 1W or W / cm or W / cm2 or W / cm3 or W per cm of a body part or body It can be kept below W per cm2 of body part or W per cm3 of body part.

[0263] In one embodiment of the present invention, particularly in the first step, but possibly also in the second step In the same experiment, the laser intensity was set at 10 20 , 10 9 , 10 6 , 10 3 , 10 2 , 10, or It can be kept below 1mA (milliamps).

[0264] In the experimental example, the laser intensity is fixed at 4500 A, and a power density of 2 W / cm 2 is used, which is sufficient to induce a temperature increase e of the magnetic nanoparticles, in particular magnetosomes, and does not induce a temperature increase of water alone, not comprising the magnetic nanoparticles In the experimental example, the laser intensity was fixed at 4500 mA and the W / cm 2 is used, which is the temperature of the magnetic nanoparticles, especially the magnetosomes. Water alone is sufficient to cause an increase and does not contain magnetic nanoparticles, particularly magnetosomes. In one embodiment of the present invention, the current is less than 4500 mA, particularly less than 1.0 01, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Low with a coefficient exceeding and / or 2 W / cm 2 Lower, especially 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 It is lower by a factor of 100, but still causes a temperature rise during the heating step. This is achieved in particular by: i) The magnetic nanoparticle, in particular magnetosome, concentration is adjusted to 1.001, 1.01, 1.1, 1 .5, 2, 5, 10, or 10 3 ii) the duration of the heating step Duration, specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 or iii) the temperature rise or gradient you wish to achieve during heating. Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Exceeds Decrease by a factor.

[0265] In one embodiment of the present invention, the laser intensity is determined by a factor of 100, which is a factor that generates or induces laser radiation at a particular power. In one embodiment, the laser intensity is related to the laser power. In one embodiment, a calibration curve can be constructed to relate laser intensity to laser power. can be established.

[0266] In one embodiment of the present invention, too high a laser power, power density, or laser intensity is particularly Toxic or overheating or too high a proportion of compounds from magnetic nanoparticles, especially magnetosomes or to allow cooling during the cooling step.

[0267] In some other embodiments of the invention, particularly in the first step, but possibly also In the second step, the laser power is also 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1 , 10, 10 3 , or 10 5 W or W / cm or W / cm 2 or W / cm 3 or body part W per cm of product or cm of body part 2 W per or cm of body part 3 Maintaining a W above It will be held.

[0268] In yet other embodiments of the present invention, particularly in the first step, but possibly In the second step, the laser intensity is also 10 -20 , 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10, 10 3 , 10 5 , or 10 10 mA.

[0269] In the experimental example, the laser intensity is fixed at 4500 A, and a power density of 2 W / cm 2 is used, which is sufficient to induce a temperature increase e of the magnetic nanoparticles, in particular magnetosomes, and does not induce a temperature increase of water alone, not comprising the magnetic nanoparticles s, in particular magnetosomes. In the example experiment, the laser intensity was fixed at 4500 mA and 2 W / cm 2 The power density used is This is sufficient to cause a temperature increase in the magnetic nanoparticles, especially the magnetosomes, Water alone that does not contain magnetic nanoparticles, especially magnetosomes, does not cause a rise in temperature. In the embodiment, the current is higher than 4500 mA, in particular 1.001, 1.01, 1.1, 1.5, 2 , 5, 10, or 10 3 and / or a laser intensity that is a factor exceeding Specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Coefficient exceeding It is possible to use power densities greater than 2 W / cm2 at 1000 Hz. In particular magnetosomes, magnetic nanoparticles, in particular regions of magnetosomes or magnetic nanoparticles, in particular This causes an increase in temperature in some body parts that contain magnetosomes, especially magnetic nanoparticles, Body parts that do not contain magnetosomes or magnetic nanoparticles, especially magnetosomes, in This is achieved by: i) the magnetic nanoparticles do not induce a temperature rise outside the The concentration of particles, especially magnetosomes, was increased to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 ii) the duration of the heating step Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Exceeds or iii) specify the temperature rise or temperature gradient you wish to achieve during heating. by a factor of 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or greater than 103 To increase.

[0270] In some other embodiments of the invention, particularly in the first step, magnetic nanoparticles, particularly magnetosomes, The room can be heated or a sufficiently large proportion of the compound can be magnetic nanoparticles, especially magnetic nanoparticles. Sufficiently high laser power or laser power should be used to result in dissociation of the nematodes from the nematodes. The laser power density or intensity is desired.

[0271] In one embodiment of the present invention, the laser power or laser power density or laser intensity is In the first step, the temperature of the part of the body that contains the magnetic nanoparticles, specifically magnetosomes, is increased. In one embodiment of the present invention, the temperature of the body part is maintained at a level sufficient to raise the temperature of the body part. The increases are 10 -6, 10 -3, 10 -1, 1, 5, 10, 10 2 , or 10 3 From ℃ expensive.

[0272] In some other embodiments of the present invention, the temperature rise of the body part is 10 6 , 10 3 , 10 , 1, or 10 -1 Lower than °C.

[0273] In one embodiment of the invention, the temperature increase designates the temp erature increase of the body part, portion of the body part comprising the magne tic nanoparticles, in particular the magnetosomes, region of the magnetic nanoparticles rticles, in particular the magnetosomes, region, or the magnetic nanoparticles, in particular the magnetosomes. In one embodiment of the present invention, the temperature increase is caused by the presence of magnetic nanoparticles, particularly magnetosomes, in the body part. Parts of body parts, including magnetic nanoparticles, particularly magnetosomes, regions, or areas of magnetic material, particularly magnetosomes The temperature increase of the gnetosome is shown. The temperature increase can be assimilated to or correspond to the magnitude of the temperature increase occurring in the first step, which is preferentially t he absolute value of the difference between the maximum and minimum temperature reached in the second step, which is also in one embodiment designated as temperate ature variation or temperature variation during or occurring in the first step. The temperature increase can be assimilated or matched to the magnitude of the temperature increase occurring in the first step. , which is the absolute value of the difference between the maximum and minimum temperatures reached in the first step, This also refers to temperature fluctuations or temperature changes that occur during or in the first step in one embodiment. Specified as a variation.

[0274] In another embodiment of the present invention, the laser power or power density or laser intensity is In one step, the compound is dissociated from the magnetic nanoparticles, particularly magnetosomes. The temperature is kept high enough to

[0275] In one embodiment of the present invention, the percentage dissociation of the compound from the magnetic nanoparticles, in particular from magnetosomes, is 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 25, 50, 75, or 90 It can be more than %.

[0276] In some other embodiments of the present invention, compounds from magnetic nanoparticles, particularly magnetosomes, are The dissociation percentage of is 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 25, 50, 75, 9 It may be 0 or lower than 99%.

[0277] In another embodiment of the invention, magnetic nanoparticles, in particular magnetosomes, are included in the first step. To prevent heating of parts of the body that are not keeps the laser intensity low enough.

[0278] In another embodiment of the invention, in the first step, the laser power or the laser power density Alternatively, the laser intensity can be kept low enough to prevent the formation of nuclei from magnetic nanoparticles, especially magnetosomes. Prevents dissociation of the compound.

[0279] In one embodiment of the present invention, the laser wavelength is defined as the wavelength of the laser emission or the wavelength of the laser radiation. It can be specified or corresponded to.

[0280] In yet another embodiment of the present invention, in the first step, the laser wavelength is 10 20 , 10 15 , 10 9 , 10 7 , 10 5 , 10 4 , 1000, 900, 800, 700, 50 Maintained at or below 0, 100, 50, 20, 2, or 1 nm .

[0281] In yet another embodiment of the present invention, in the first step, the laser wavelength is 10 20 , 1 0 15 , 10 9 , 10 7 , 10 5 , 10 4 , 1000, 900, 800, 700, 500 , 100, 50, 20, 2 or 1 nm or longer. ..

[0282] In yet another embodiment of the present invention, in the first step, the laser wavelength is between 1 nm and 1 Between 00000nm, between 1nm and 10000nm, between 20nm and 5000nm, between 50 between 100 nm and 1000 nm, or between 2000 nm and 2000 nm.

[0283] In one embodiment of the present invention, electromagnetic radiation, particularly related to or corresponding to laser radiation, is , 1, 2, 5, 10, or 10 3 It includes over 100 different vibration frequencies.

[0284] In yet another embodiment of the present invention, electromagnetic radiation specifically associated with or corresponding to laser radiation is 2, 5, 10, or 10 3 The vibration frequencies include different frequencies less than 100 Hz.

[0285] In yet another embodiment of the present invention, the electromagnetic radiation, particularly in connection with laser radiation, is a magnetic field or are different from or not alternating magnetic fields.

[0286] In yet another embodiment of the present invention, in the first step, the laser wavelength is Corresponding to or resulting from strong absorption of light by particles, especially magnetosomes The resulting values ​​are fixed, i.e. specifically 10000, 5000, 2000, 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 50, 2 The wavelength is less than 0, 10, 5, 2, or 1 nm.

[0287] In yet another embodiment of the invention, particularly in the first step, the laser wavelength is is fixed at a value that results in strong absorption or transmission of light into or through the item or object, It is especially important to note that the 10000, 5000, 2000, 1000, 900, 800, 700, 60 0, 500, 400, 300, 200, 100, 50, 20, 10, 5, 2, or 1n m or 10000-1nm, 5000-1nm, 5000, 10nm , 5000-100nm, or 2000nm-200nm.

[0288] In yet another embodiment of the invention, particularly in the first step, the laser wavelength is It is possible to reach maximum coupling between the surface plasmon waves of nanoparticles, especially magnetosomes, and laser radiation. and is fixed to a wavelength that allows

[0289] In the experimental example, the laser wavelength is fixed at 808 nm.

[0290] In one embodiment of the present invention, the laser wavelength is selected to reduce the absorption of the laser radiation by the body parts. , 2, 5, 10, 10 3 , or 10 6 In order to increase by a factor exceeding 1.001, 1.01 , 1.1, 10, 10 3 , or 10 6 can be increased by a factor of more than

[0291] In some other embodiment of the invention, this laser wavelength can be decreased d, preferentially by a factor of more than 1.001, 1.01, 1.1, 10, 10 3 , or 10 6 , pr eferentially to enhance absorption of the laser radiation by the magnetic nanopa rticles, in particular magnetosomes, preferentially by a factor of more than 1.0 01, 1.01, 1.1, 10, 10 3 , or 10 6 . In some other embodiments of the present invention, the laser wavelength is preferably 100 nm or more, more preferably 100 nm or more. In order to enhance the absorption of laser radiation by the tosomes, especially 1.001, 1.01, 1.1 , 10, 10 3 , or 10 6 can be reduced by a factor of more than

[0292] In one embodiment of the present invention, the magnetic nanoparticles, particularly magnetosomes, obtained in the first step are The percentage of dissociation of these compounds is 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 25,5 It can be 0, 75, or 90%.

[0293] In some other embodiments of the present invention, the magnetic nanoparticles, especially the maganese nanoparticles, that are obtained in the first step are The percentage of dissociation of the compound from the glnetosomes is 10 -5 , 10 -3 , 10 -1 , 1, 5, It may be lower than 10, 25, 50, 75, 90, or 99%.

[0294] Furthermore, in some cases, the magnetic nanoparticles obtained in the first step, especially magnetos The rate of dissociation of the compound from the gel is 10 -5 -99%, 10 -3 -99%, 10 -1 -9 It can be 9%, 1-99%, 10-99%, 10-0%, or 25-75%.

[0295] The second step is in particular to administer the magnetic nanoparticles during or at the body part or to the magnetic nanoparticles, in particular to the magnetic nanoparticles. The gnetosomes are irradiated with a lower power laser than in the first step. Alternatively, the second step may involve the application of magnetic particles, in particular body parts, or magnetic nanoparticles, in particular magnets. Alternatively, the second step is a step in which the tosome is not irradiated by laser radiation. The technique involves the use of magnetic nanoparticles, especially magnetosomes, or laser irradiation of body parts. This is not a step.

[0296] In one embodiment of the present invention, the laser power or laser power density or laser intensity is a second In the step, the amount of the 1.1, 1.2, 1.5, 2, 5, 10, 1 0 3 , 10 6 , 10 9 , or 10 20 Twice lower.

[0297] In the experimental example, the laser is turned off in the second step. To avoid heating the child, especially the magnetosomes or body parts, the laser power If is low enough, it is possible to keep the laser on during the step. In practice, this avoids damaging the laser by turning it on and off too many times. It may be useful to

[0298] In yet another embodiment of the present invention, in the second step, the laser wavelength is From the laser wavelength used in the experiment, The distance between the surface and the surface is maintained at different values ​​of 00, 500, 100, 50, 20, 2, or 1 nm or less.

[0299] In yet another embodiment of the present invention, in the second step, the laser wavelength is From the laser wavelength used in , 700, 500, 100, 50, 20, 2, or 1 nm or more different.

[0300] In yet another embodiment of the present invention, in the second step, the laser wavelength is Corresponding to or resulting in weak absorption of light by the nuclei, especially magnetosomes, or The resulting wavelengths are fixed, i.e. specifically 1, 5, 10, 100, 200, 30 0, 400, 500, 600, 700, 800, 900, 1000, 2000, 5000 , or wavelengths greater than 10,000 nm.

[0301] In yet another embodiment of the present invention, in the second step, the laser wavelength is The coupling between the surface plasmon waves of molecules, especially magnetosomes, and the laser radiation reaches a minimum. and is fixed to a wavelength that allows

[0302] In one embodiment of the present invention, the first and second steps are at least 1, 2, 3, 4, 5, 10, 100, 10 3 , 10 5 , or 10 10 is repeated times.

[0303] In one embodiment of the present invention, the first and second steps are 1, 2, 3, 4, 5, 10, 100, 10 3 , 10 5 , or 10 10 Repeated less times.

[0304] In yet another embodiment of the present invention, the first step and the second step are 10times , 2-10 5 Innings, 2-10 5 Innings, 2-10 3 Times 5-10 3 times, or 10-10 3 Repeat It will be repeated.

[0305] In one embodiment of the present invention, the sequence of the first and second steps is at least 1, 2 , 3, 4, 5, 10, 100, 10 3 , 10 5 , or 10 10 is repeated times.

[0306] In another embodiment of the invention, the sequence of the first and second steps is 1, 2, 3, 4, 5, 10, 100, 10 3 , 10 5 , or 10 10 It is repeated less than a certain number of times.

[0307] In yet another embodiment of the present invention, the sequence of the first and second steps is from 2 to 10 10 times, 2 to 10 5 times, 2 to 10 3 times, 5 to 10 3 times, or 10 and 10 3 times Repeated.

[0308] In one embodiment of the present invention, the duration of the first and / or second steps is 10 -50 , 10 -1 0 , 10 -1 , 1, 5, 10, 15, 30, 100, 10 3 , 10 5 or 10 10 Longer than a minute.

[0309] In some other embodiments of the invention, the duration of the first and / or second steps is 10 -50 , 10 -10 , 10 -1 , 1, 5, 10, 15, 30, 100, 10 3 , 10 5 or 10 10 From short.

[0310] In still other embodiments of the present invention, the duration of the first and second steps is 1 0 -50 -10 50 minutes, 10 -50 -10 3 minutes, 10 -50 -60 minutes, 10 -50 -30 minutes, more specifically 10 -5 -30 minutes, more specifically 10 -3 -15 minutes, more specific 10 in terms of -1 -10 minutes, or more specifically, 10 -1 -5 minutes.

[0311] In one embodiment of the present invention, an inter-step period separates the first step from the second step. It is a period or elapsed time.

[0312] In one embodiment of the present invention, the inter-step period is 10 -1 0-10 20 Minutes, especially 10 -5 - 10 5 minutes, more specifically 10 -5 It may be -10 minutes. Even more particularly 10 - 5 -1 minute.

[0313] In one embodiment of the present invention, the inter-step duration is 10 5 , 10 3 , 100, 60, 30 , 15, 10, 5, 2, 1, 10 -1 or 10 -3 or 10-10 It's okay if it's less than a minute stomach.

[0314] In some other embodiments of the present invention, the inter-step period is 10 -10 , 10 -3 , 10 -1 , 1, 5, 10, 10 3 , 10 5 , 10 10 or 10 20 It may be longer than a minute.

[0315] In particular, the duration of the first step induces a temperature rise, which is especially important for the magnetic nanoparticles in the body parts. Long enough to allow release of at least one compound.

[0316] Especially the duration of the second step induces a temperature drop, especially in the body parts, and the magnetic nano Long enough to prevent release of at least one compound from the particle.

[0317] In particular, the duration of the first and second steps may affect cell destruction, immune stimulation, immune suppression, or enzyme activity. Biological processes such as the production or appearance of biological substances such as DNA, RNA, and proteins. effect, long enough to induce.

[0318] In particular, the duration of the first and / or second step is such that the temperature is constant or Short enough to avoid maintaining a stable temperature for: i) more than a day, especially 1 minute; most particularly 1 second, or ii) more than 50% of the duration of the first step, where this percentage The rate is the time elapsed during which the temperature is maintained constant versus the total duration of the first step. It is a ratio.

[0319] In particular, the duration of the first and / or second step is The loop is short enough that it can be repeated multiple times.

[0320] In yet another embodiment, the first step and the second step are performed with an inter-step period. It can be separated by the time between: i) the laser The power of the first step is set to 0 or a value lower than the first step value, especially at the start of the second step. Start time, timing t 1 and the percentage of dissociation of the compound or the temperature rise is particularly small. At least 1.1, 1.2, 1.5, 5, 10, 10 3 , 10 5 or 10 10 With a higher coefficient, less weight is given Time t when it is no longer necessary 2 or ii) the power of the laser is set to a value other than zero; or to a value higher than that of the second step, especially at the beginning of the first step. ngt 3 and the percentage of dissociation of the compound or the temperature increase, especially in the second step. At least 1.1, 1.2, 1.5, 5, 10, 10 3 , 10 5 or 10 10 Significant with a higher coefficient than The timing t 4 In other words, the inter-step duration is particularly At the beginning of the second step, the laser power is set to a certain value and the laser is turned on. There may be a time lapse separating the time when the body part and / or nanoparticles are effective. The effect is in particular a change in the percentage dissociation of the compound and / or a change in the temperature increase. The effect is an effect that occurs or is measured specifically in body parts and / or nanoparticles. be.

[0321] In one embodiment of the present invention, the inter-step duration is t 1 -t 2 or t 3 -t 4 Equal to It could be.

[0322] The order of the first and second steps is also called the sequence, and the first step is followed by The second step follows.

[0323] In one embodiment, the duration of the sequence is 10 -50 , 10 -10 , 10 -1 , 1, 5, 10, 15, 3 0, 100, 10 3 , 10 5 or 10 10 It may be longer than a minute.

[0324] In some other embodiments, the duration of the sequence is 10 -50 , 10 -10 , 10 -1 , 1, 5, 10, 15, 30, 100, 10 3 , 10 5 or 10 10 It may be shorter than a minute.

[0325] In yet some other embodiments, the duration of the sequence is 10 -50 -10 50 minutes, Especially 10 -50 -10 3 minutes, more specifically 10 -50 -60 minutes, more specifically 10 -50 -30 minutes, more specifically 10 -5 -30 minutes, more specifically 10 -3 -15 minutes , and more specifically 10 -1 -10 minutes, or more specifically, 10 -1 -5 minutes.

[0326] In one embodiment, the duration of the sequence is greater than the first duration and / or the second duration. is at least 0, 1, 1.01, 1.1, 1.5, 2, 5, 10, 10 3 , 10 5 or 10 10 Especially twice It can be made longer.

[0327] Two consecutive sequences of the first and second steps are separated by an inter-sequence duration The inter-sequence duration may vary between each sequence. or the same.

[0328] In one embodiment, the intersequence duration is 10 5 , 10 3 , 100, 60, 30, 15, 10, 5, 2, 1, 10 -1 or 10 -3 or 10 -10 In particular, the medical or antitumor activity This is useful if a sequence needs to be repeated quickly to reach

[0329] In some other embodiments, the length between the sequences is 10 -10 , 10 -3 , 10 -1 , 1, 5, 10, 10 3 , 10 5 , 10 10 or 10 20 This is because the patient is especially if you need to recover from a treatment or procedure, for example if the treatment procedure involves anesthesia. or intolerable clinical protocols such as surgery, chemotherapy, radiation therapy or immunotherapy This is beneficial when combined with or requires use of

[0330] In yet some other embodiments, the intersequence duration is 10 -10 From 10 20 for a minute , 10 -5 From 10 5 For 10 minutes -5 Between 10 minutes and 10 -5 Within 1 minute of could be.

[0331] In one embodiment, the duration between sequences is at least 0, 1, 1.1, 2, 5, 10, 10 3 , 10 5 or 10 10 Twice as long.

[0332] In yet some other embodiments, the inter-sequence duration is longer than the inter-step duration. Also at least 0, 1, 1.1, 2, 5, 10, 10 3 , 10 5 or 10 10 Twice as short.

[0333] In particular, the sequence or duration between sequences may affect cell destruction, immune stimulation, immune suppression, etc. biological effects or the production or production of biological substances such as enzymes, DNA, RNA, proteins, etc. Long enough to induce emergence.

[0334] In particular, the duration of a sequence or between sequences may be determined by the time at which the sequence can be repeated. and particularly large enough to achieve a therapeutic efficacy. .

[0335] In one embodiment, the duration of at least one sequence is at least one step in particular at least 1.1 times longer than the duration of The duration of the step is at least 1.1 times longer than the duration of at least one interstep. long.

[0336] In yet another embodiment of the present invention, the number of sequences per unit time is 10 per second. -50 , 10 -20 , 10 -10 , 10 -5 , 10 -3 , 10 -1 , 1, 10, or 10 3 Greater than a sequence.

[0337] In yet another embodiment of the present invention, the number of sequences per unit time is 10 per second. -50 , 10 -20 , 10 -10 , 10 -5 , 10 -3 , 10 -1 , 1, 10, or 10 3 is less than.

[0338] In the experimental example, the number of sequences per unit time was 8 per second for 0.5 mg / mL M-CMD. 10 -3 Sequence: 10 per second for 1 mg of M-CMD -2 A sequence of, and 1 7-10 mg N-CMD per second -3 In one embodiment, the sequence Sequence numbers, specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 More than twice as many It is possible to increase the number of magnetic nanoparticles, especially magnetosomes, by: i) increasing the concentration of magnetic nanoparticles, especially magnetosomes; Degrees specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10 or 10 3 increase by a factor greater than ii ) especially 1.001, 1.01, 1.1, 1.5, 2, 5, 10 or 10 3 Heating steps are multiplied by more than Increase the laser power during the cooling phase or decrease the laser power during the cooling phase, iii) specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10 or 10 3 Achieved by a factor of over Decrease the temperature rise in the heating step or the temperature drop in the cooling step you are about to perform ,The number of sequences per unit time is calculated in the following way, specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10 or 10 3 i) magnetic nanoparticles, especially magnetic nanoparticles, can reduce the magnetic flux density by a factor of more than The concentration of gnetosomes was specifically adjusted to 1.001, 1.01, 1.1, 1.5, 2, 5, 10 or 10 3 Exceeds ii) To decrease by a factor, especially 1.001, 1.01, 1.1, 1.5, 2, 5, 10 or 10 3 Exceeding Decrease the laser power during the heating step or increase the laser power during the cooling step by a factor of or iii) increase the output, especially 1.001, 1.01, 1.1, 1.5, 2, 5, 10 or 10 3 The temperature increase in the heating step or cooling step you are trying to achieve is a factor of more than The treatment sessions are performed in several sequences, especially 1, 2, 5, 10 , 10 3 or 10 5 It is a series of sequences exceeding 1000.

[0339] In one embodiment, the period between at least two treatment sessions is equal to the period between two sequences. This may occur especially during or during medical protocols. or where i) the patient is treated with a method or treatment according to the invention. In particular, several sequences following one another should be performed in order to obtain optimal medical activity. ii) several of these sequences corresponding to one session At the end of the session, for example due to patient pain or fatigue or long anesthesia, the two sequences may be repeated. the treatment or method must be stopped for a period of time that is significantly longer than the period between treatments, For example, if a patient treated by the method or treatment has undergone prolonged anesthesia or is fatigued, or due to lack of availability of medical infrastructure or medical teams.

[0340] In one embodiment, the duration of a treatment session is 10 -50 , 10 -10 , 10 -1 , 1, 5, 10, 15, 30, 100, 10 3 , 10 5 or 10 10 It can be longer than a minute.

[0341] In some other embodiments, the duration of a treatment session is 10 50 , 10 10 , 60, 30, 10, 5 , 2, 1, 10 -1 or 10 -5 It can be less than a minute.

[0342] In yet some other embodiments, the duration of a treatment session is 10 -50 Minutes and 10 50 For a minute, Especially 10 -50 Minutes and 10 3 For 10 minutes, more specifically -50 Between 10 and 60 minutes, and more specifically between 10 and 60 minutes -50 Between minutes and 30 minutes, and more specifically 10 -5Between minutes and 30 minutes, and more specifically 10 -3 Minutes and 1 For 5 minutes, and more specifically 10 -1 Between minutes and 10 minutes, or even more specifically 10 -1 minutes and five It can be between minutes.

[0343] The first treatment session is separated from the second session by an intersession duration. obtain.

[0344] In one embodiment, the inter-session period is 10 5 , 10 3 , 100, 60, 30, 15, 10, 5, 2 , 1, 10 -1 or 10 -3 or 10 -10 This may be shorter than 1 minute, particularly in medical or When rapid repetition of sessions is necessary to achieve antitumor activity It could be.

[0345] In some other embodiments, the inter-session period is 10 -10 , 10 -3 , 10 -1 , 1, 5, 10, 10 3 , 10 5 , 10 10 or 10 20 This may be for longer than 10 minutes, for example if the treatment method involves the use of anesthesia. or if the patient is unable to tolerate surgery, chemotherapy, radiation therapy and / or immunotherapy. Combined with or requiring the use of challenging clinical protocols , if the patient needs to specifically recover from a treatment or method between two sessions, etc. There may be times when a treatment or method needs to be stopped for a period of time.

[0346] In yet some other embodiments, the inter-session period is 10 -10 Minutes and 10 20 For a minute, especially 1 0 -5 Minutes and 10 5 More specifically, for 10 minutes -5 Between minutes and 10 minutes, and more specifically 10 minutes -5 Minutes and minutes It is between .

[0347] In one embodiment, the inter-session duration is longer than the inter-sequence or inter-step duration. Also at least 0, 1, 1.1, 2, 5, 10, 10 3 , 10 5 or 10 10 Twice as long.

[0348] In yet some other embodiments, the inter-session period is between sequences or steps. Intervals of at least 0, 1, 1.1, 2, 5, 10, 10 3 , 10 5 or 10 10 Only twice as short.

[0349] In one embodiment, a treatment session comprises: 1a +t 2a or t 1b +t 2b From 1.001, 1.01, 1.1, 1. 2, 1.5, 2, 5, 10, 10 3 , or 10 5 can be separated by more than two times the duration .

[0350] In one embodiment of the present invention, a treatment session may be 2, 5, 10, 100, or 10 4 Repeated more than once can be.

[0351] In another embodiment of the present invention, the treatment sessions are 5, 10, 100, 10 4 , or 10 5 Repeated less than once will be returned.

[0352] In another embodiment of the present invention, the number of treatment sessions and / or sequences is determined based on the maximum treatment time. To achieve the desired effect, i.e. to suppress the progression of a disease in a part of the body that contains, for example, pathological cells or tumors. Adjusted to achieve disappearance or destruction.

[0353] In yet another embodiment of the present invention, the number of treatment sessions and / or sequences is To minimize toxicity, i.e., loss or destruction of parts of the body that contain healthy cells. is adjusted to avoid destruction.

[0354] The sequential laser irradiation of the present invention is surprisingly more efficient and / or has fewer side effects. While the thermal stress is small, it allows for lower heating temperatures of the body parts than with continuous laser irradiation. The treatment of the present invention is particularly a magnetohydrodynamic treatment without performing at least the first and second steps. The average heating temperature is lower than the average temperature achieved by continuously irradiating the beam with a laser. to heat body parts.

[0355] In one embodiment, during the first step and / or the second step, the The heating temperature of the body part being heated is less than 100% of the duration of the step, in particular 50% and more particularly 1 0% or less, or 10 5 Seconds, especially 10 3 seconds, and more particularly within less than 10 seconds.

[0356] Without wishing to be bound by theory, the sequential laser irradiation of the present invention is The laser is more effective than continuous laser irradiation, especially in suppressing the activation of pathological cells against healthy cells. Ratio wise more efficient and / or with fewer side effects.

[0357] In one embodiment, the treatment is a treatment for a decrease in the number of activated pathological cells Npat selected from the group consisting of: The method produces a result having at least one characteristic that is - the value of Npat, which is 1, cm of a particular body part 3 Greater than 1 per. - The value of Npat / Nhealth, where Nhealth is the number of healthy cells greater than 1. - Npat or Npat / Nhealth value, which is the value of the magnetosome when continuously irradiated with laser light is greater than that obtained by exposing it to wherein the activated pathological cells have at least one characteristic selected from the following: ) cells contained in the pathological site or magnetosome region, ii) cells contained in the pathological site or magnetosome region Are attracted to, migrate toward, or divide in the glnetosome region? iii) Cells that are specifically targeted to the tumor before, during or after treatment. iv) cells that are viable when not in use, especially by apoptosis or necrosis, especially during treatment or dead or destroyed cells after or during treatment or when treatment is efficient, v) cells that promote the growth or maintenance of pathological sites, and vi) cells that promote the destruction or maintenance of pathological sites. are cells that prevent loss, where healthy cells have at least one characteristic of the group consisting of: i) cells in healthy areas or regions that do not contain magnetosomes; ii) cells in healthy areas or regions that do not contain magnetosomes. Attracted to or migrated toward areas without magnetosomes or regular sites iii) a cell that migrates or migrates or divides or grows; Cells that are viable during or after treatment or when treatment is effective, i.v. ) especially before or when treatment is ineffective, especially apoptosis or Cells that have died or been destroyed by necrosis; v) cells that promote the growth or maintenance of healthy tissue. and vi) cells that prevent the destruction or disappearance of healthy areas.

[0358] In one aspect, the present invention relates to the use of magnetic nanoparticles, in particular magnetosomes, Here, the first step is a heating step and a dissociation step.

[0359] In one aspect, the present invention provides magnetic nanoparticles, particularly magnetic nanoparticles, for use according to the present invention. or a method according to the invention, wherein the first step further comprises heating and and / or the dissociation of at least one compound from the magnetic nanoparticles, in particular magnetosomes.

[0360] In one embodiment of the present invention, the heating step refers to the duration or heating time of the heating step. Duration t 1a has.

[0361] In one embodiment, the duration of the heating step is adjusted to accommodate the body parts, the magnetic nanoparticles, in particular magnetosomes, or corresponds to a period of temperature increase in the region of the magnetic nanoparticles, in particular magnetosomes. At the next time t i1a ,i) ,Laser start, ii) ,Switch on the laser equipment or device, iii ) in particular body parts, magnetic nanoparticles, in particular magnetosomes, or magnetic nanoparticles, in particular magnetosomes The start of irradiation of the region of the soma with laser light, and then at the next time t f1a ,i) Laser ii) switching off the laser device or equipment; iii) preventing irradiation by laser radiation. End, or iv) time t iaby lower power laser radiation in, especially, body parts, Magnetic nanoparticles, particularly magnetosomes, or regions of magnetic nanoparticles, particularly magnetosomes Irradiation.

[0362] In one embodiment, the magnetic nanoparticles, particularly magnetosomes, i1a A certain period of time Dt i1a、 body Parts, magnetic nanoparticles, particularly magnetosomes, or regions of magnetic nanoparticles, particularly magnetosomes The temperature of the device is increased or begins to increase.

[0363] In one embodiment of the present invention, the magnetic nanoparticles, particularly magnetosomes, are f1a For a certain period of time following W 10;t f1a , body parts, magnetic nanoparticles, particularly magnetosomes, or magnetic nanoparticles, particularly magnetosomes The endothelial cell stops causing or inducing an increase in temperature in the region of the endothelium.

[0364] In one embodiment of the present invention, Dt i1a and Dt f1a is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, or This long delay, in one embodiment, includes magnetic nanoparticles, particularly magnetosomes. Laser irradiation by body parts that are not magnetic or by substances other than magnetic nanoparticles, especially magnetosomes. In some other embodiments, this long delay can be attributed to the absorption of radiation by magnetic nanoparticles. Laser irradiation, especially by magnetosomes or body parts containing magnetic nanoparticles, especially magnetosomes This may be due to the absorption of laser radiation, particularly where it is not immediately converted or transferred to heat.

[0365] In some other embodiments of the present invention, Dt i1a and Dtf1a is 10 -9 , 10 -6 , 10 -3 , 10 -1 The short delay is, in one embodiment, less than 1, 2, or 10 seconds. by absorption of laser radiation by the netosome and its rapid conversion or transfer to heat It could be.

[0366] In still other embodiments of the present invention, Dt i1a and Dt f1a The value of is the magnetic nanoparticle Organisation of magnetosomes, magnetic nanoparticles, especially from magnetosomes, magnetic nanoparticles, The transfer of heat to the surroundings or environment of magnetosomes, or to magnetic nanoparticles, particularly magnetosomes The size, ferrimagnetic properties, and crystallization of the material depend on the intrinsic properties of the material. Dt i1a and Dt f1a by improving the crystallization of magnetic nanoparticles, especially magnetosomes. By increasing the size of magnetic nanoparticles, especially magnetosomes, By narrowing the size distribution of magnetosomes, magnetic nanoparticles, especially magnetosomes, can be By improving the spatial distribution of the magnetic field or magnetic nanoparticles in particular in body parts In particular, this can be reduced by reducing magnetosome aggregation.

[0367] In the experimental example, Dt f1a is equal to 0 seconds for M-CMD at 0.5 and 1 mg / mL, and equal to 0 seconds for N-CMD at 0.5 and 1 mg / mL. D is between 6 and 16 seconds. This is especially true for chemically synthesized or well-crystallized Some of the unexposed nanoparticles continue to heat up even after the laser is switched off. This results in overheating and a precise temperature for the temperature reached during the heating step. It is a property that should usually be avoided, since it can interfere with control. Some nanoparticles are produced by living organisms or are well crystallized. indicates that the heating stops immediately after the laser is switched off. This prevents overheating. , which allows precise control of the temperature reached during the heating step, A characteristic that is usually desired or cared for.

[0368] In one embodiment of the present invention, the dissociation step is also Called duration t 1b has.

[0369] In one embodiment, the duration of the dissociation step is such that the compounds from the magnetic nanoparticles, particularly magnetosomes, are dissociated. It corresponds in particular to the period of dissociation of the laser, the switching of the laser device or apparatus. Inserting a magnetic nanoparticle, especially a magnetosome, or a magnetic nanoparticle, especially a magnetosome, into a body part The time t of the start of irradiation of the magnetosome area by laser radiation i1b And the laser stops. The time t when the laser device or apparatus is switched off or when irradiation with laser radiation ends f 1b is included between.

[0370] In one embodiment, the magnetic nanoparticles, particularly magnetosomes, are Dissociation of a compound from t i1b A time before or after Dt i1b begins to generate or induce

[0371] In one embodiment of the present invention, the magnetic nanoparticles, particularly magnetosomes, are f1bSome time before or after Between Dt f1b to stop the formation or dissociation of compounds from magnetic nanoparticles, particularly magnetosomes. .

[0372] In one embodiment of the present invention, Dt i1b and Dt f1b is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, or This long delay, in one embodiment, allows the magnetic nanoparticles, particularly magnetosomes, to Laser radiation from body parts that do not contain magnetic nanoparticles, especially magnetosomes, or from substances other than magnetic nanoparticles In some other embodiments, this long delay can be attributed to the absorption of radiation by magnetic nanoparticles. Laser irradiation with magnetosomes or body parts containing magnetic nanoparticles, especially magnetosomes - due to the absorption of radiation, which immediately dissociates compounds from magnetic nanoparticles, especially magnetosomes. will not start.

[0373] In some other embodiments of the present invention, Dt i1b and Dt f1b is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, or less than 1 second. This short delay, in one embodiment, is achieved by the magnetic nanoparticles, particularly the magnetic This may be due to the absorption of laser radiation by the netosomes, which may be due to the magnetic nanoparticles, in particular This results in rapid dissociation of the compound from the magnetosomes.

[0374] In yet some other embodiments of the present invention, Dt i1b Especially Dt f1b The value of is the magnetic nanoparticle In particular, the composition of magnetosomes, the strength of binding between the compounds and magnetic nanoparticles, in particular magnetosomes the distance between the compound and the magnetic nanoparticles, particularly magnetosomes; It depends on the properties of the chromosomes, such as size, ferrimagnetism, or crystallization. So, Dt i1b and Dt f1b improves the crystallization of magnetic nanoparticles, especially magnetosomes. By increasing the size of magnetic nanoparticles, especially magnetosomes, By narrowing the size distribution of magnetic particles, especially magnetosomes, the magnetic nanoparticles, especially magnetosomes, can be By improving the spatial distribution of magnetosomes, it is possible to specifically target magnetic nanoparticles in body parts. By reducing the aggregation of magnetosomes, the compound and magnetic nanoparticles, especially magnetosomes, This can be reduced by adjusting the intensity or distance between the laser and the Immediately after irradiation with the ionizing radiation, irradiation with laser radiation causes the magnetic nanoparticles, especially magnetosomes, to separate. Induces dissociation of the compound.

[0375] In another embodiment of the present invention, the first step comprises: 1a or t 1b Equal to, or t 1a Ma or 1b longer than, or t 1a or t 1b has a shorter duration than

[0376] In one embodiment of the present invention, the heating step is carried out on the body part or on magnetic nanoparticles, in particular magnets. tosome, 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, 10, or 15°C above the It is particularly useful for treating cancer at temperatures above physiological temperatures or with magnetic nanoparticles, particularly magnetosomes. the temperature of the body parts that does not contain the laser radiation or reach before the laser radiation hits the body parts temperature or higher than the temperature of the magnetic nanoparticles before or without exposure to laser radiation. stomach.

[0377] In one embodiment of the present invention, the dissociation step is carried out during or in which the compound is attached to the magnetic nanoparticles. In particular, the step of dissociating from magnetosomes. , 75, or even more than 90% of the compounds dissociate from the magnetic nanoparticles, especially magnetosomes. The compounds are assumed to dissociate from the magnetic nanoparticles, particularly magnetosomes.

[0378] In particular, the dissociation rate refers to the rate of dissociation of the compound from the magnetic nanoparticles, particularly magnetosomes. and this is designated the percentage of dissociation.

[0379] In particular, the variation in the percentage of dissociation is most particularly the variation in the percentage of dissociation during the dissociation or non-dissociation step. The percentage change over time.

[0380] In particular, the gradient of the dissociation percentage is most particularly the gradient of the dissociation percentage, the dissociation or non-dissociation step. Most specifically, this slope is the slope of the time course of the dissociation percentage. It is an absolute value.

[0381] In one embodiment, the percentage of dissociation of the compound from the magnetic nanoparticles, in particular from magnetosomes, is particularly Magnetic nanoparticles, especially magnetosomes, unbound or The number of unwound compounds was measured, especially for magnetic nanoparticles before and after laser irradiation. divided by the number of compounds bound or wrapped around the particle, especially the magnetosome, This corresponds to the following.

[0382] In an embodiment of the present invention, the compound that dissociates from the magnetic nanoparticles, particularly magnetosomes, is They may belong to the coating or core of nanoparticles, or may be metal atoms such as iron. In addition, iron can dissociate from magnetosomes after irradiation of the magnetosomes. In some embodiments, irradiation directly results in dissociation of the compound from the magnetic nanoparticles. That is, dissociation may depend on other factors than laser irradiation, such as cells or a specific medium, such as an acidic medium. In some other embodiments, irradiation does not result in dissolution of the compound from the magnetic nanoparticles. This indirectly induces the release of the laser radiation from the cells or the specific medium. The entity dissociates the compound, particularly after activation by a laser or after laser irradiation. Sometimes it can cause dissociation.

[0383] In one embodiment of the present invention, the compounds have a weak or no interaction with magnetic nanoparticles, particularly magnetosomes. The polymer comprises at least one substance capable of establishing a covalent bond.

[0384] In one embodiment of the present invention, the compounds are or are attached to magnetic nanoparticles, particularly magnetosomes, can be chemisorbed or physisorbed onto the surface of magnetic nanoparticles, especially magnetosomes. The compound includes at least one compound that is

[0385] In one embodiment of the invention, the compounds are attached to the interior or surface of magnetic nanoparticles, particularly magnetosomes. At least one atom, ion, or molecule that can establish an interaction or bond with Contains one substance.

[0386] In one embodiment of the invention, a compound is a compound that ... Contains chemical functional groups, such as carboxylic acid, phosphoric acid, or sulfonic acid functional groups, where The substances, atoms, and ions contained in the coating interact with magnetic nanoparticles, especially magnetosomes. A use or connection can be established.

[0387] In one embodiment of the present invention, the dissociation percentage is the percentage of the compound dissociated after irradiation with laser radiation. The number or mass of the magnetic nanoparticles, particularly magnetosomes, bound to the magnetic nanoparticles prior to irradiation with laser radiation. It is defined as the ratio of the number or mass of compounds divided by the number or mass of compounds detected.

[0388] In another embodiment of the invention, compounds are magnetically separated from magnetic nanoparticles, particularly magnetosomes. Upon release, they dissociate from the magnetic nanoparticles, particularly magnetosomes. In this case, a magnet can preferentially be used to attract the magnetic nanopa rticle, in particular magnetosome, preferentially using a magnetic field whose i ntensity varies spatially, preferentially using a magnet with a lower strength t han 10, 1, 10-1, 10-3, or 10-9 T, where this strength is preferentially measured at the surface or near the magnet and decreases with increasing distance away f rom the magnet. In this case, specifically 10, 1, 10 -1 , 10 -3 , or 10 -9 Use magnets with a strength lower than T. In particular, magnetic fields with spatially varying strength are used to attract magnetic nanoparticles, particularly magnetosomes. A magnet can be used to measure the strength of the magnet. This strength is measured specifically at the surface of the magnet or close to the magnet. This is in contrast to magnetic nanoparticles, especially magnetosomes, which show a large magnetic flux density. Generally, compounds are not particularly attracted to magnets. Therefore, using magnetic separation Therefore, between the compound and the magnetic nanoparticles, particularly magnetosomes, 1, 10, 10 3 , or 10 5 It is possible to create a certain distance larger than nm, and then magnetic nanoparticles, especially magneto The some can be separated or isolated from the compound.

[0389] In another embodiment of the invention, the compound remains bound to the magnetic nanoparticles, in particular magnetosomes. or from magnetic nanoparticles, particularly magnetosomes. -1 , 10 -3 , 10 -6 , or 10 -9 The proportion of compounds located at a distance of 99, 90, 75, 50, 30, 20, 10, and 5 cm When the concentration is lower than 1%, 2, or 1%, the magnetic nanoparticles, especially magnetosomes, dissociate. The percentage of nucleosomes bound or associated with magnetic nanoparticles, especially magnetosomes, prior to magnetic separation. The number or mass of compounds bound or attached to magnetic nanoparticles, particularly magnetosomes, after magnetic separation. The ratio of the number or mass of the attached compound can be expressed.

[0390] In another embodiment of the invention, the compound is a magnetic nanoparticle, particularly a magnetosome, in particular 10, 1, 1 0 - 1, 10 -3 , or 10 -9 It can be magnetically separated from the compound using a magnet with a strength lower than T. If not, the magnetic nanoparticles, particularly magnetosomes, do not dissociate or are non-dissociated.

[0391] In yet another embodiment of the invention, the compounds are attached to magnetic nanoparticles, in particular magnetosomes. 10, 1, 10 attached or bound to magnetic nanoparticles, especially magnetosomes -1 , 10 -3 , 10 -6 , or 10 -9 The percentage of compounds located at distances shorter than 99, 90, or 1 cm If it is greater than 75, 50, 30, 20, 10, 5, 2, or 1%, the magnetic nanoparticles, especially the magneto This percentage is the percentage of the nucleosomes that are not dissociated or undissociated from the nucleosomes before magnetic separation. The number or mass of compounds bound or associated with magnetic nanoparticles, particularly magnetosomes, and the magnetic It represents the ratio of the number or mass of compounds bound or attached to the magnetic nanoparticles after gas separation.

[0392] The present invention relates to magnetic nanoparticles, in particular magnetosomes, for use, wherein the first step The method comprises the steps of: (a) detecting a body part during or in which a first portion of the body part is irradiated with laser radiation; The first sub-step and during or therein the production of magnetic nanoparticles, in particular magnetosomes. The increase in temperature of the compound and / or the dissociation of the compound is induced by the laser radiation during the first substep. Therefore, the second sub-step occurs in another part of the body part that is not irradiated. obtain.

[0393] In one embodiment of the invention, the body part is irradiated or illuminated by laser radiation. parts of the body part that are irradiated or not irradiated by the laser radiation The product is divided into two parts:

[0394] In yet another embodiment of the present invention, a method for treating a skin cancer is provided, comprising: The parts of a body part that are designated as a body part or part of a body part are those that are specifically This is the region in which the first part of the magnetic nanoparticles, particularly magnetosomes, is present. In the embodiment, it is designated as a first region of a magnetic nanoparticle, particularly a magnetosome.

[0395] In one embodiment of the present invention, the first region of the magnetic nanoparticle, particularly the magnetosome, is Specifically, it corresponds to less than 99, 90, 80, 70, 50, 40, 20, 10, 5, or 1% of magnetosomes. It is administered to an individual or part of the body, or is contained in a body part or individual. This percentage is magnetic nanoparticles, especially magnetosomes. and the amount of magnetic nanoparticles, particularly magnetosomes, contained in the first region of the individual or body part. expressing the ratio between the amount of magnetic nanoparticles, particularly magnetosomes, administered or contained can be done.

[0396] In one embodiment of the present invention, the body part or part of the body part is provided with magnetic nanoparticles, in particular magnetoresistance. The second portion of the chromosome is a region specifically located within the individual. In one embodiment, it is a magnetic nanoparticle. It is designated as the second region of the magnetosome, specifically the magnetosome.

[0397] In one embodiment of the present invention, the second region of the magnetic nanoparticle, particularly the magnetosome, is Especially magnetosomes 99, 90, 80, 70, 50, 40, 20, 10, 5, 1, 10 -3 or 10 -6 More than % The volume corresponds to or includes the volume that can be obtained by magnetic nanoparticles, especially magneto or the first region of the magnetic nanoparticle, in particular the magnetosome, is not located in the first region of the magnetic nanoparticle, in particular the magnetosome. a region located outside of, or different from, the first region of the magnetic nanoparticle, particularly the magnetosome Located in. This percentage is located outside the first region of the magnetic nanoparticles, particularly magnetosomes. or located in the second region of the magnetosome or magnetic nanoparticle, particularly the magnetosome The amount of magnetic nanoparticles, particularly magnetosomes, contained in or on an individual or body part may be determined. The ratio is divided by the amount of magnetic nanoparticles, particularly magnetosomes, administered.

[0398] In yet another embodiment of the present invention, the period between the first and second sub-steps is , 1, 10 -3 , 10 -6 , or 10 -9 Less than a second.

[0399] In yet another embodiment of the invention, the magnetic nanoparticles, in particular the magnetosomes, are located in the second region. Heating magnetic nanoparticles, especially magnetosomes, or metal nanoparticles that are prone to dissociation of compounds The mechanism is that the first and second regions of thermally conductive or magnetic nanoparticles, especially magnetosomes, Magnetic nanoparticles, particularly magnetosomes, can involve the conduction or transmission of electromagnetic waves between the High concentration or magnetic nanoparticles, particularly magnetosomes, are particularly chain-like or densely packed together When tightly coupled, this may be advantageous for thermal conduction and / or electromagnetic wave transmission or transmission. do.

[0400] In one embodiment of the present invention, the thermal conduction and the electromagnetic wave transmission or conduction are achieved by using magnetic nanoparticles, especially magnetic nanoparticles. Between gnetosomes and tissue or water contained in the body part, or between water molecules within the body part This occurs especially between moving water molecules. The movement of water molecules is especially increased by heat. do.

[0401] The present invention also relates to the use of magnetic nanoparticles, in particular magnetosomes, in which the second step The steps are a cooling step and a de-dissociation step.

[0402] In one embodiment of the present invention, the cooling step is performed in a time-dependent manner, as well as the duration or cooling time of the cooling step. Called duration t 2a has.

[0403] In one embodiment of the present invention, the duration of the cooling step is such that the body parts, magnetic nanoparticles, in particular magnetoresistance, This corresponds to a period of temperature decrease in the region of the magnetosomes, or of the magnetic nanoparticles, particularly the magnetosomes. This includes, in particular, stopping the laser, switching off the laser device or device, laser output , a decrease in laser power density or laser intensity, or termination of irradiation by laser irradiation. At the time i2a , and starting the laser, switching on the laser device or device, or laser The time t when irradiation begins f2a is included between.

[0404] In one embodiment of the present invention, the temperature reduction is achieved by administering to the body part, magnetic nanoparticles, particularly magnetosomes, The temperature of some body parts, including magnetic nanoparticles, particularly magnetosomes, is reduced. can be assimilated or corresponded to the magnitude of the temperature drop that occurs in the second step. It is in particular the absolute value of the difference between the maximum and minimum temperatures reached in the second step, Also in one embodiment, the temperature fluctuation or temperature fluctuation occurring during or at the second step It is.

[0405] In one embodiment of the present invention, the magnetic nanoparticles, particularly magnetosomes, are i2a before or after Time Dt i2a In the present invention, a magnetic nanoparticle, in particular a magnetosome, or a magnetic nanoparticle, This causes or induces a decrease in temperature in the region of the nanoparticles, particularly the magnetosomes.

[0406] In one embodiment of the present invention, the magnetic nanoparticles, particularly magnetosomes, are f2a A certain time before and after Dt f2a In the present invention, a magnetic nanoparticle, in particular a magnetosome, or a magnetic nanoparticle, in particular a magnetosome, is It ceases to cause or induce a decrease in temperature in the region of the glnetosome.

[0407] In one embodiment of the present invention, Dt i2a and Dt f2a is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, or This long delay, in one embodiment, is from the magnetic nanoparticles, particularly magnetosomes. , to the environment or medium surrounding the magnetic nanoparticles, particularly magnetosomes, or to the magnetic nanoparticles This may be due to slow or inefficient release or transfer of heat, especially to body parts that do not contain magnetosomes. This may be the cause.

[0408] In one embodiment of the present invention, this heat emission or transfer occurs at a rate of 10 -20 , 10 -10 , 10 -4 , 10 -2 , 10 -1 , 1, 10, 10 2 , 10 5 , 10 10 , or 10 20 °C or slower.

[0409] In some other embodiments of the present invention, Dt i2a and / or Dt f2a is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, or less than 10 seconds. In one embodiment, the short delay is In particular from magnetosomes to the environment or medium surrounding the magnetic nanoparticles, in particular magnetosomes. or to body parts that do not contain magnetic nanoparticles, particularly magnetosomes, for rapid or efficient delivery of heat. This may be by spontaneous release or transmission.

[0410] In one embodiment of the present invention, this heat emission or transfer occurs at a rate of 10 -20 , 10 -10 , 10 -4 , 10 -2 , 10 -1 , 1, 10, 10 2 , 10 5 , 10 10 or 10 20 Faster than °C.

[0411] In yet some other embodiments of the present invention, Dt i2a and / or Dt f2a The value of is the magnetic Organization of magnetic particles, especially magnetosomes, and magnetic nanoparticles, especially magnetosomes, from the surroundings or surroundings to the environment, or to body parts that do not contain magnetic nanoparticles, in particular magnetosomes or magnetic nanoparticles; It also depends on the properties of the magnetic nanoparticles, especially magnetosomes, e.g. In one embodiment of the present invention, Dt i2a and / or Dt f2a improves the crystallization of magnetic nanoparticles, especially magnetosomes, Increase the size of magnetosomes and narrow the size distribution of magnetic nanoparticles, especially magnetosomes. Improve the spatial distribution of magnetic nanoparticles, especially magnetosomes, especially in body parts. This can be reduced by reducing the aggregation of magnetic nanoparticles, especially magnetosomes.

[0412] In the experimental example, Dt f2a is equal to 0 seconds for M-CMDs between 0.5 and 1 mg / mL, and is equal to 0 seconds for N-CMDs between 0.5 and 1 mg / mL. It is between 6 and 25 seconds. It is especially useful for chemically synthesized or well-crystallized Note that some nanoparticles do not cool down within the same period of time as the laser is switched off. This can result in supercooling and a positive deviation from the temperature reached during the cooling step. It is a property that is usually to be avoided, since it can prevent accurate control. Some nanoparticles are specifically produced artificially or by living organisms, or are well crystallized. This shows that the neutron particles cool down in the same period as the laser is switched off. This is a characteristic to be aware of, as it prevents overcooling and This is because it allows precise control of the temperature reached during the step.

[0413] In one embodiment of the present invention, the non-dissociation step is determined by the duration of the non-dissociation step or the time of non-dissociation. Duration t, also called interval 2b has.

[0414] In one embodiment of the present invention, the period of the non-dissociation step is such that the magnetic nanoparticles, in particular magnetosomes, are free from dissociation. It corresponds in particular to the period of non-dissociation of the compounds from the laser, the laser device or is the time t when the device is switched off and irradiation by the laser radiation ends i2b And start the laser, The time when the laser device or device is switched on, the time when irradiation with laser radiation begins t f2b is included between.

[0415] In one embodiment of the present invention, the magnetic nanoparticles, particularly magnetosomes, are i2b after or before At some time Dt i2b , the generation of non-dissociated compounds from magnetic nanoparticles, especially magnetosomes, or Begin induction.

[0416] In one embodiment of the present invention, the magnetic nanoparticles, particularly magnetosomes, are f2b A certain time before and after Dt f2b Subsequently, the generation or induction of non-dissociation of compounds from magnetic nanoparticles, particularly magnetosomes, Stop.

[0417] In one embodiment of the present invention, Dt i2b and / or Dt f2b is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, or longer than 10 seconds. This long delay Dt i2b after the laser has been switched off or the power Release of compounds from magnetic nanoparticles, particularly magnetosomes, for extended periods of time after the force has been reduced. This long delay Dt f2b is the time after the laser is switched on. This may be due to the compound starting to dissociate over time.

[0418] In some other embodiments of the present invention, Dt i2b and / or Dt f2b is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, or less than 10 seconds. This short delay Dt i2b The laser is switched off. During the initial power or short time after the power is reduced, magnetic nanoparticles, particularly magnetosomes, This may be due to the completion of dissociation of the compound. This short delay may occur for Dt f2b be due to the beginning of the dissociation of th e compound a short time after the laser has been switched on. This short delay Dt f2b The dissociation of the compound occurs a short time after the laser is switched on. This may be due to the start of

[0419] In still other embodiments of the present invention, Dt i2b and / or Dt f2b The value of is the magnetic The organization of magnetic particles, especially magnetosomes, and the binding between compounds and magnetic nanoparticles, especially magnetosomes The intensity of the interaction, the distance between the compound and the magnetic nanoparticles, particularly magnetosomes, the magnetic nanoparticles, particularly magnetosomes, It depends on properties such as the size of the gnetosomes, their ferrimagnetic properties, or their crystallization.

[0420] In one embodiment of the present invention, Dt i2b and / or Dt f2b Magnetic nanoparticles, especially magnetospheric Improved the crystallization of the magnetic nanoparticles, increased the size of the magnetic nanoparticles, especially magnetosomes, and The size distribution of magnetic nanoparticles, especially magnetosomes, is narrowed, and the void space of magnetic nanoparticles, especially magnetosomes, is improved. Improve spatial distribution and reduce aggregation of magnetic nanoparticles, especially magnetosomes, especially in body parts. By reducing the amount of the magnetic flux, the strength or distance between the compound and the magnetic nanoparticles, particularly magnetosomes, can be adjusted. As a result, the laser Termination of irradiation by radiation stops the dissociation of the compound from the magnetic nanoparticles, particularly magnetosomes. The dissociation is inhibited or non-dissociation is induced.

[0421] In another embodiment of the present invention, the second step comprises: 2a or t 2b Equal to or t 2a Ma or 2b longer than, or t 2a +t 2b has a shorter duration than

[0422] In one embodiment of the present invention, the cooling step is performed during or at the body part or magnetic nanoparticles. The particles are cooled or the temperature is lowered below the maximum temperature reached during the heating step. 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, 10, or 15 °C or more.

[0423] In one embodiment of the present invention, the non-dissociation step is performed during or at which the compound is attached to the magnetic nanoparticles. This is a step in which the molecules, especially magnetosomes, do not dissociate from the magnetosomes.

[0424] In one embodiment of the present invention, the compounds do not dissociate from the magnetic nanoparticles, particularly magnetosomes, and The percentage of dissociation at time is less than 0.1, 1, 10, 25, 50, 75, or 90%.

[0425] In another embodiment of the present invention, at time t 1a , t 1b , t 2a , or t 2b , is 10 -3 , 10 -2 , 10 -1 , 1 , 10, 10 2 , or 10 3 Less than a minute.

[0426] In one embodiment of the present invention, t 1a , t 1b , t 2a , or t 2b , is 10 -9 , 10 -7 , 10 -5 , 10 -3 , 10 -1 , 1, 10, 10 3 , 10 5 , 10 7 , or 10 9 Less than a second.

[0427] In yet another embodiment of the present invention, at time t 1a , t 1b , t 2a , or t 2b , is 10 -3 , 10 -2 , 10 -1 , 1, 10, 10 2 , or 10 3 Longer than a minute.

[0428] In one embodiment of the present invention, t 1a , t 1b , t 2a , or t 2b is 10 -9 , 10 -7 , 10 -5 , 10 -3 , 10 - 1 , 1, 10, 10 3 , 10 5 , 10 7 , or 10 9 Longer than seconds.

[0429] In one embodiment of the present invention, time t 1a , t 1b , t 2a , or t 2b Especially at least 1.1, 1.5 , 2, 5, 10, 10 2 , 10 3 , 10 5 , 107 , 10 9 , 10 12 , 10 15 , or 10 20 Laser pulse with a factor of is shorter than the time.

[0430] In yet another embodiment of the present invention, at time t 1a , t 1b , t 2a , or t 2b In particular, at least one .1, 1.5, 2, 5, 10, 10 2 , 10 3 , 10 5 , 10 7 , 10 9 , 10 12 , 10 15 , or 10 20 The rate is increased by a factor of Longer than The Pulse time.

[0431] In yet another embodiment of the invention, the pulse is in particular magnetic nanoparticles, in particular magnetosomes, to the body parts, or to the area of ​​magnetic nanoparticles, particularly magnetosomes, 10 6 , 10 3 , 1, 10 -3 , 10 - 6 , 10 -9 , 10 -12 , 10 -15 , or 10 -20 As irradiation with laser radiation for periods of less than a second is defined.

[0432] In one embodiment of the present invention, the ratio t 1a / t 2a or t 1b / t 2b is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 1 0, 10 3 , 10 6 , or 10 9Less than.

[0433] In yet another embodiment of the present invention, the ratio t 1a / t 2a or t 1b / t 2b is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10, 10 3 , 10 6 , or 10 9 Greater than.

[0434] In the experimental example, t 1a for 0.5 mg / mL M-CMD between 35 and 150 seconds, and for 1 mg / mL M-CMD for N-CMD, it is between 21 and 80 seconds, and for N-CMD, it is between 22 and 45 seconds.

[0435] In one embodiment of the present invention, t 1a Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 ,of It is possible to reduce the temperature by a factor of over 100 and still cause a temperature rise during the heating step. This can be achieved by, in particular, i) increasing the concentration of magnetic nanoparticles, in particular magnetosomes, Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Increase by a factor greater than ii) laser power, laser power density, or laser intensity, in particular 1.001, 1. 01, 1.1, 1.5, 2, 5, 10, or 10 3 or ii. i) During the heating step, the desired temperature increase or gradient is achieved, especially at 1.001, 1.01, 1.1, 1.5, 2 , 5, 10, or 10 3 This can be achieved by reducing the luminance by a factor of more than

[0436] In yet another embodiment of the present invention, the body is free of magnetic nanoparticles, especially magnetosomes. without causing a rise in the temperature of the components, 1a , especially 1.001, 1.01, 1.1, 1.5, 2, 5, 10 , or 10 3 and cause a temperature rise during the heating step. This can be achieved by: i) increasing the concentration of magnetic nanoparticles, particularly magnetosomes, to 1.001 , 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 ii) the laser power is reduced by a factor of , laser power density, or laser intensity, especially 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or is 10 3 or iii) the temperature increase you want to achieve during the heating step. or temperature gradients, specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 By a factor exceeding This can be achieved by raising

[0437] In the experimental example, t 2a between 60 and 75 seconds for 0.5 mg / mL M-CMD and 1 mg / mL M-CM between 65 and 90 seconds for D, and between 89 and 105 seconds for N-CMD.

[0438] In one embodiment of the present invention, t 2a Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 of It is possible to reduce the temperature by a factor of more than 100 and still cause a temperature drop during the cooling step. This can be achieved by: i) reducing the concentration of magnetic nanoparticles, especially magnetosomes, to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 ii) reduce the rate by a factor greater than Laser power, laser power density, or laser intensity, specifically 1.001, 1.01, 1.1, 1.5, 2, 5 , 10, or 10 3 iii) the desired temperature reduction during the cooling step or temperature gradients, specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 By a factor exceeding This can be achieved by reducing

[0439] In still other embodiments of the present invention, the method does not include magnetic nanoparticles, particularly magnetosomes. without inducing a temperature drop in the body parts 2a Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 It is possible to increase the temperature by a factor of more than This can be achieved by, in particular, i) increasing the concentration of magnetic nanoparticles, in particular magnetosomes, Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 ii) increase by a factor greater than Laser power, laser power density, or laser intensity, specifically 1.001, 1.01, 1.1, 1.5 , 2, 5, 10, or 10 3 or iii) during the cooling step The desired temperature drop or gradient can be set to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Exceeding This can be achieved by reducing the

[0440] In the experimental example, the first sequence is not taken into account, and t 1a / t 2a0 for 0.5 mg of M-CMD Between 0.6 and 0.7, equal to 0.3 for 1 mg of M-CMD, and between 0.2 and 0.4 for 1 mg of N-CMD. Between.

[0441] In one embodiment of the present invention, the ratio t 1a / t 2a Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 In particular, the magnetic field can be increased by a factor of more than The density of the spherosomes can be set to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10. 3 Decreased by a factor of more than ii) increasing the laser power to, among other things, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Exceeding This can be done by reducing it by a factor of

[0442] In some other embodiments of the present invention, the ratio t 1a / t 2a Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5 , 10, or 10 3 can be reduced by a factor of more than Specifically, the magnetosome concentration was adjusted to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Exceeding ii) increase the laser power by a factor of 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 This can be done by increasing it by a factor exceeding

[0443] In yet another embodiment of the present invention, the cooling time is determined by the presence of magnetic nanoparticles, particularly magnetosomes. Absence is greater than 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 More than long.

[0444] In yet another embodiment of the present invention, the heating time is adjusted to reduce the non- in the absence of 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Multiples greater than And it's long.

[0445] In one aspect of the invention, the present invention provides magnetic nanoparticles, particularly magnetospheric nanoparticles, for use according to the invention. or a method according to the invention, wherein the first step of heating comprises at least group and has an average temperature below 100 °C. The heating is performed at a uniform heating temperature. - an average heating temperature that is in particular at least 1°C lower than the maximum temperature reached during treatment. - Maximum heating temperature is less than 100℃ - Sequential irradiation of magnetic nanoparticles, particularly magnetosomes, after two steps involving irradiation. The average heating temperature reached by laser irradiation is In particular at least 1°C lower than the temperature reached by continuous irradiation, - the number of heating gradients greater than 2, and - after at least two steps including irradiation, magnetic nanoparticles, in particular magnetosomes, Multiple heating temperature gradients achieved by sequential laser irradiation, which is particularly Multiple heating gradients achieved by sequentially irradiating the gnetosome with a laser In particular, the heating temperature gradient is at least twice as large as the heating temperature in the first step. degree rise, especially in the 10 -1 , greater than 1, 5 or 10°C. In one embodiment of the present invention, the heating temperature of at least one first step is at least Any temperature or at least one of the temperatures reached during one of the first steps.

[0446] In one embodiment of the present invention, the average heating temperature, in particular for at least one first step, is (THS max +THS min ) / 2 or (THS 1 +THS 2 +…THS i) / i, where 1 <i<n、THS i Heating Step heating temperature, THS min is the minimum heating temperature of the heating step, THS max is the first heating step The large heating temperature, i, is an integer between 1 and n.

[0447] In one embodiment of the present invention, the average heating temperature of at least one first step is preferably 10 10 , 10 7 , 10 5 , 10 3 , 500, 250, 150, 100, 70, 50 or lower than 20 °C.

[0448] In one embodiment of the present invention, the average heating temperature of at least one first step is preferably -273°C, -200, -100, -50, 0, 5, 10, 20, 37, 40, 42, 50, 55, 60, 70 or higher than 90 °C .

[0449] In one embodiment of the present invention, the average heating temperature in particular in at least one first step is -273 and 10 10 °C between -100 and 10 5 °C between 0 and 10 3 °C between 20 and 10 3 Between 37 and 1 °C 0 3 °C, between 37 and 100 °C.

[0450] In one embodiment of the present invention, the average heating temperature is at least one step, at least one sequence, at least one session or step, sequence, and session The average heating temperature or average temperature of the entire process including

[0451] In one embodiment of the present invention, the maximum heating temperature is at least one step or at least The maximum heating temperature for at least one sequence, or at least one session, or the entire treatment degrees or its maximum temperature.

[0452] In one embodiment of the present invention, the minimum heating temperature is at least one step or at least At least one sequence, or at least one session, or the entire process The hot or coldest temperature.

[0453] In one embodiment of the present invention, the average heating temperature of at least one first step is At least one heating step, at least one sequence, or at least one Especially at least 10°C above the maximum temperature reached during one session -5 , 1, 5 or 10 °C Low.

[0454] In one embodiment of the present invention, in particular the temperature of at least one first step, in particular the maximum heating temperature is 10 5 , 10 3 , 500, 250, 100, 75 or lower than 50 °C.

[0455] In one embodiment of the present invention, the temperature, in particular the maximum heating temperature, in particular the temperature of at least one first step The temperatures are -273, -200, -100, -50, -20, -10, -5, 0, 5, 10, 20 or 37 °C. .

[0456] In one embodiment of the present invention, the temperature, in particular the maximum heating temperature, in particular the temperature of at least one first step The temperatures are -273 and 10 5 °C between -100 and 10 3 Between °C, between 0 and 100, between 37 and 70 °C or between 30 and 60°C.

[0457] In one embodiment of the present invention, the minimum heating temperature of at least one first step is in particular At least one of the first steps is at least 10° C. -10 , 10 -5 , 10 -3 , 1 0 -1 , 1, 5, 10 or 50 °C lower.

[0458] In one embodiment of the present invention, the minimum heating temperature is, in particular, the highest heating temperature of at least one first step. Especially 10% higher than heat temperature 10 , 10 5 , 10 3 , by less than 100, 50, 20, 10, 5 or 1 °C lower.

[0459] In one embodiment of the present invention, the magnetic nanoparticles are delivered by sequential laser irradiation. The average heating temperature is the average temperature reached by continuously irradiating the magnetic nanoparticles with a laser. At least 10% higher than the heating temperature -10 , 10 -5 , 10 -1 , 1, 5 or 10 °C lower. The average heating temperature reached by continuous laser irradiation of a nanoparticle is (T max +T min ) / 2 or (T 1 +T 2 +…T i) / i, where 1 <i <n、Ti is the number of consecutive processing sessions. is the temperature, T min is the minimum temperature during the continuous treatment period, and T max is the maximum temperature during the continuous treatment period where i is an integer between 1 and n inclusive.

[0460] In one embodiment of the present invention, at least one of the first steps, in particular at least one seed Heating included in the sequence and included during at least one session or during the entire process The number of temperature gradients is specifically 2, 5, 10, 10 3 or 10 5 The heating temperature gradient is smaller. Both can be a single first step temperature increase.

[0461] In one embodiment of the present invention, in particular at least one sequence, at least one session The number of heating gradients in at least one first step in the process or in the overall process is 10 10 , 10 5 , 10 3 , 500, 250, 100, 50, 20, 10, 5 or less than 2.

[0462] In one embodiment of the present invention, in particular at least one sequence, at least one session The number of heating gradients in at least one first step in the process or in the overall process is 2 to 10 5 Between 2 and 10 3 or between 2 and 100.

[0463] In one embodiment of the present invention, the magnetic nanoparticles are delivered by sequential laser irradiation. The number of heating temperature gradients is greater than the number of heatings, and the magnetic nanoparticles are continuously irradiated with the laser. The number of temperature gradients achieved by the or 10 3 , twice as big.

[0464] In one embodiment of the present invention, the comparison between sequential and continuous treatments is based on at least one of the sequential treatments or methods. Compare at least one treatment session of a continuous treatment or method This is done by comparing

[0465] In one embodiment of the present invention, the heating temperature gradient is a temperature increase in the heating step, in particular at least 1 where the temperature rise of the heating step is the temperature rise of the heating step can be defined as the change in temperature with time that occurs between successive temperature If there is only an increase or a continuous increase in temperature, or if the fluctuation is not a decrease in temperature, This is considered a combination.

[0466] In one embodiment of the present invention, the change in temperature over time is an increase in temperature, and such a change is 10 in size -5 , 10 -3 , 10 -1 , greater than 1, 5 or 10 °C.

[0467] In one aspect, the present invention provides magnetic nanoparticles, in particular magnetic nanoparticles, for use according to the present invention. The netosomes or the method according to the invention, wherein the second step comprises cooling and / or or non-dissociation of at least one compound from magnetic nanoparticles, in particular magnetosomes. .

[0468] In one aspect of the invention, the present invention provides magnetic nanoparticles, in particular magnetrons, for use according to the invention. The method according to the present invention, wherein the cooling step of the second step is (1) the average cooling temperature is greater than 0°C; and (2) Number of cooling gradients greater than or equal to 2 Here, the cooling temperature gradient is, in particular, 10 -1 , 1, 5 or 10°C higher It is a decline, A method characterized by at least one characteristic selected from the group consisting of the cooling temperature It is law.

[0469] In one embodiment of the present invention, the cooling temperature of at least one second step is at least Any temperature or at least one of the temperatures reached during one of the second steps.

[0470] In one embodiment of the present invention, the average cooling temperature of at least one second step is preferably greater than or equal to (TCS ma x +TCS min ) / 2 or (TCS 1 +TCS 2 +…TCS i) / i, where 1 i Cooling station The cooling temperature of the cooling step, TCS max is the minimum cooling temperature of the cooling step and TCS max is the maximum cooling temperature of the cooling step, and i is an integer between 1 and n It is.

[0471] In one embodiment of the present invention, the average cooling temperature of at least one second step is preferably 10 10 , 10 7 , 10 5 , 10 3 , 500, 250, 150, 100, 70, 50 or lower than 20 °C.

[0472] In one embodiment of the present invention, the average cooling temperature of at least one second step is preferably -273​ , -200, -100, -50, 0, 5, 10, 20, 37, 40, 42, 50, 55, 60, 70 or below 90 °C stomach.

[0473] In one embodiment of the present invention, the average cooling temperature of at least one second step is between -273 and 10 10 °C between -100 and 10 5 °C between 0 and 10 3 °C between 20 and 10 3 Between 37 and 10 °C 3 °C, or between 37 and 100 °C.

[0474] In one embodiment of the present invention, the average cooling temperature is determined in at least one step, at least one The average cooling temperature or average It is the uniform temperature.

[0475] In one embodiment of the present invention, the maximum cooling temperature is determined in at least one step, at least one sequence, at least one session, or step, sequence, session This is the maximum cooling temperature or maximum temperature of the entire process including

[0476] In one embodiment of the present invention, the minimum cooling temperature is determined in at least one step, at least one The minimum or maximum cooling temperature for the sequence, at least one session, or the entire process It is a low temperature.

[0477] In one embodiment of the present invention, the average cooling temperature, in particular during at least one second step, is During treatment, at least one cooling step, at least one sequence, or Also, the lowest temperature reached during one session should be at least 10 -5, 1, 5 or 10 Only °C higher.

[0478] In one embodiment of the present invention, the temperature, in particular the temperature of at least one second step or Minimum cooling temperature is -273, -200, -100, -50, 0, 5, 10, 20, 37, 10 or higher than 45 °C stomach.

[0479] In one embodiment of the present invention, the temperature, in particular the minimum cooling temperature of at least one second step, Degrees are 100, 70, 60, 55, 50, 45, 40, 37, 30, 20, 0, -10, -50 or below -100 °C. stomach.

[0480] In one embodiment of the present invention, the temperature of at least one second step is preferably at least 100° C., more preferably at least 150° C. Degrees, temperatures are -273 and 10 5 , -100 and 10 3 , between 0 and 100, 37 and 70, or 30 and 60 °C be.

[0481] In one embodiment of the present invention, the maximum cooling temperature of at least one second step is in particular At least one second step at least 10% lower than the minimum cooling temperature -10 , 10 -5 , 10 -3 , 1 0 -1 , 1, 5, 10 or 50 °C higher.

[0482] In one embodiment of the present invention, the maximum cooling temperature of at least one second step is in particular At least one of the second step minimum cooling temperatures, especially 10 10 , 10 5 , 10 3 , 100, 50, 20 , less than 10, 5 or 1 °C higher.

[0483] In one embodiment of the present invention, in particular, at least one session during at least one sequence The cooling gradient of at least one second step during the process or during the entire process. The numbers are 2, 5, 10, and 10. 3 or 10 5 The cooling gradient is greater than or equal to at least one The second step may be a decrease in temperature.

[0484] In one embodiment of the present invention, in particular, at least one session during at least one sequence The cooling gradient of at least one second step during the process or during the entire process. The number of distributions is 10 10 , 10 5 , 10 3 , 500, 250, 100, 50, 20, 10, 5 or greater than 2.

[0485] In one embodiment of the present invention, in particular, at least one session during at least one sequence The cooling gradient of at least one second step during the entire process or during The number of distributions is from 2 to 10. 5 , 2 to 10 3 , or between 2 and 100.

[0486] In one embodiment of the present invention, the cooling temperature gradient is a temperature drop in the cooling step, in particular at least 1 The temperature drop in the cooling step is the temperature drop that occurs over time. can be defined as the temperature fluctuation that occurs due to a continuous decrease in temperature. The temperature drop is a constant or continuous decrease in temperature and the fluctuations are not temperature increases.

[0487] In one embodiment of the present invention, the temperature change over time is a decrease in temperature, where the magnitude of the change is The size is 10-5 , 10 -3 , 10 -1 , greater than 1, 5 or 10 °C.

[0488] The present invention also relates to the use of magnetic nanoparticles, in particular magnetosomes, in which the heating step The cup causes a temperature increase of more than 1°C in body parts.

[0489] In one embodiment of the present invention, the heating step is carried out on the body parts, magnetic nanoparticles, in particular magnetosomes. or in the region of or within magnetic nanoparticles, particularly magnetosomes. -9 , 10 -6 , 10 -3 , 10 -1 , causing a temperature increase of 1, 2, 5, or 10 °C or more, especially above physiological temperatures, or above the temperature of the body parts prior to or without irradiation with laser radiation. be.

[0490] In the experimental example, the temperature is reached between the second and eighth heating steps, separate from the first sequence. The temperature rise is equal to the maximum temperature minus the minimum temperature of the heating step, but is the average of: i) 8 °C for 0.5 and 1 mg / mL M-CMD, and ii) 1 mg / mL N-CMD for 12 °C, where M-CMD and N-CMD are 2 W / cm 2 is exposed to a laser power density of

[0491] In one embodiment of the present invention, in particular 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Exceeds A higher temperature rise can be reached with a factor of 10, which is due to i) the use of magnetic nanoparticles, especially magnetospheric Set the concentration of the drug to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3increase by a factor greater than i i) The duration of the heating step can be set to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Exceeds iii) the temperature rise or temperature gradient to be reached during the heating step, especially .001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 or iv) increase by a factor of more than After switching off the laser, wait 10 seconds after the laser is off. -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10, 10 3 , or 10 6 For more than 10 seconds, especially using magnetic nanoparticles, particularly magnetosomes, -9 , 10 -6 , 10 -3 , 10 -1 , 1, 10, 10 3 , or 10 6 By continuing to heat to above 20°C, It becomes Noh.

[0492] In one embodiment of the present invention, the heating step is measured at any given time during the heating step. and the temperature gradient (DT) of or within body parts that contain magnetic nanoparticles, particularly magnetosomes. / dt)t 1a which generates 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, or 10 °C / sec or higher It is also not a substitute for any magnetic nanoparticles, particularly magnetosomes, that may occur in body parts in the absence of such nanoparticles. More specifically, 1.1, 1.2, 2, 5, 10, 50, 10 2 , 10 3 , or 10 5 Below Higher at higher magnification.

[0493] In one embodiment of the present invention, (DT / dt)t 1a is the temperature change over time that occurs during the heating step It is defined as the slope of the tangent to

[0494] In one embodiment of the present invention, and (DT / dt)t 2a are the time periods measured by t1a and t1b, respectively. is the absolute value of the slope of the tangent to the temperature change

[0495] In one embodiment of the present invention, t 1a Specifically, greater than 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 100 When it increases by a factor of 0, (DT / dt)t 1a Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or It decreases by a factor of over 100. This is because (DT / dt)t 1a is closer to the beginning of the th step than to the end This means that the temperature change with time measured at the beginning of the heating step is The initial gradient of the transformation is (DT / dt)t 1a This means that it is the maximum value of .

[0496] In one embodiment of the present invention, the laser power, laser power density, laser intensity, and / or or magnetic nanoparticles, especially magnetosomes, at concentrations of 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5 , 10, or even more than 100, during the heating step (DT / dt)t 1a , can reduce the variation between different values ​​of (DT / dt)t 1a , The variation is 99, 90, 85, 75, 60, 50, 30, 20, 10, 5, 2, 1, or 10 -1 It is less than %. The percentage of [(DT / dt)t 1a1 -(DT / dt)t 1a2 ] / (DT / dt)t 1a1 where ((DT / dt)t 1a1 and (DT / dt)t 1a2 are two different times t 1a1 and 1a2 Measured in This is the temperature gradient.

[0497] In yet another embodiment of the present invention, the average temperature gradient of the heating step is 1a Measured The specified (DT / dt)t 1a is the average value of 1a Different values ​​of for a similar period, or 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 5, 10, 50, or longer than 100 seconds Separated by period (DT / dt)t 1a The average value of Av[(DT / dt)t 1a ].

[0498] In one embodiment of the present invention, Av[(DT / dt)t 1a ] is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, or Higher than 10 °C / sec.

[0499] In some other embodiments of the present invention, Av[(DT / dt)t 1a ] is 10 6 , 10 3 , 10, 5, 2, 1, and is 10 -3 °C / sec.

[0500] In the example experiment, the average temperature gradient during the heating step ranged from 0.13 to 0.21° for 0.5 mg of M-CMD. C / sec, 0.22 to 0.4 °C / sec for 1 mg of M-CMD, and 0.33 and 0.56 °C / sec for N-CMD. Seconds.

[0501] In one embodiment of the present invention, the temperature gradient or average temperature gradient of the heating step is in particular 1.001 , 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 can be increased by a factor of more than , i) The concentration of magnetic nanoparticles, in particular magnetosomes, was set to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 or ii) increase the laser power or laser power density by a factor greater than Degrees, specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Increase by a factor greater than This can be done by:

[0502] In some other embodiments of the invention, the temperature gradient or average temperature gradient of the heating step is: Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 can be reduced by a factor of more than i) the concentration of magnetic nanoparticles, particularly magnetosomes, is increased to 1.001, 1.01, 1.1, 1.5 , 2, 5, 10, or 10 3 or ii) reduce the laser power or laser output by a factor of more than Specifically, you can set the power density to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Decreased by a factor of more than This can be done by making

[0503] The present invention also relates to a method of using magnetic nanoparticles, in particular magnetosomes, which comprises a cooling step causes a temperature drop of more than 1°C in a body part.

[0504] In one embodiment of the present invention, the cooling step is carried out on the body parts, magnetic nanoparticles, in particular magnetosomes. , or 10 in the region of magnetic nanoparticles, especially magnetosomes. -9 , 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, or a temperature drop of more than 10 °C below the maximum temperature reached during the heating step bring about.

[0505] In the experimental example, the temperature drop reached during the cooling step is the minimum temperature minus the maximum temperature. The absolute value of is equal to i) 8 °C for 0.5 and 1 mg / mL M-CMD, and ii) 1 mg / mL 12 °C for N-CMD, where M-CMD and N-CMD are the average of It is not irradiated by laser radiation.

[0506] In one embodiment of the present invention, in particular 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Exceeds A temperature drop of 1000 μm can be achieved by the following: i) of magnetic nanoparticles, especially magnetosomes Concentrations can be specified as 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Increase or decrease by a factor greater than ii) reduce the duration of the cooling step, especially to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or is 10 3 or iii) the temperature reduction you want to achieve during the cooling step. Or the temperature gradient can be set to 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Large with a coefficient exceeding To listen.

[0507] In one embodiment of the present invention, the cooling step includes measuring at any given time during the cooling step. Temperature gradient of or within the body part being subjected to, (DT / dt)t 2a or (DT / dt)t 2a Produces the absolute value of , it is 10 -9 , 10 -6 , 10 -3 , 10 -1 , greater than 1, 2, 5, or 10 °C / sec, or 1.1, 1 than any temperature gradient that occurs in body parts that do not contain magnetic nanoparticles, especially magnetosomes. .2, 2, 5, 10, 50, 10 2 , 10 3 , or 10 5 In one embodiment, (DT / dt )t 2a is defined as the slope or absolute value of the tangent of the temperature change occurring during the cooling step. It is possible.

[0508] In one embodiment of the present invention, t 2a is 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 100 or more times When it increases at a rate of (DT / dt)t 2a Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 100 or more This is the factor (DT / dt)t 2a starts at the end of the second or cooling step This could mean that the temperature is higher at the beginning of the cooling step. The initial gradient of temperature change is (DT / dt)t 2a It can mean that the maximum value of

[0509] In one embodiment of the present invention, the laser power, laser power density, laser intensity, and / or or magnetic nanoparticles, especially magnetosomes, at concentrations of 1.001, 1.01, 1.1, 1.5, 2, 5, 1 It can be increased by 0 or by a factor of over 100, which allows different cooling steps. (DT / dt)t measured during the time 2a The variation between different values ​​of 1.001, 1.01, 1.1, 1.5, 2, 5, 1 It can be reduced by a factor of 0 or by more than 100.

[0510] In one embodiment of the present invention, (DT / dt)t 2a are 99, 90, 85, 75, 60, 50, 30, 20, 10, 5, 2, 1 , or 10 -1 This percentage varies by less than (DT / dt)t 2a1 -(DT / dt)t 2a 2 / (DT / dt)t 2a1 where (DT / dt)t 2a1 and (DT / dt)t 2a2 teeth, Two different times for the cooling step t 2a1 and t 2a2 is the temperature gradient measured at

[0511] In yet another embodiment of the present invention, the average temperature gradient of the cooling step is 2a Measured is the average of the values ​​determined, and the t 2a In particular, different values ​​of . For a similar period, or 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 5, 10, 50, or longer than 100 seconds are separated by period.

[0512] In one embodiment of the present invention, Av[(DD / dt)t2a] is 10 -9 , 10 -6 , 10-3 , 10 -1 , 1, 2, 5, or Higher than 10 °C / sec.

[0513] In one embodiment of the present invention, Av[(DD / dt)t2a] is 10 6 , 10 3 , 10 -3 , 5-1, 2, 1, 5, or 10 °C / sec.

[0514] In the example experiment, the average temperature gradient of the cooling step ranged from 0.1 to 0.13 °C / s for 0.5 mg of M-CMD. sec, 0.09 and 0.12 °C / sec for 1 mg of M-CMD, and 0.11 and 0 for N-CMD. .14°C / sec.

[0515] In one embodiment of the present invention, the temperature gradient or average temperature gradient of the cooling step is in particular 1.001 , 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 can be increased by a factor of more than , i) The concentration of magnetic nanoparticles, particularly magnetosomes, was increased to 1.001, 1.01, 1.1, 1.5, 2, 5, 10 , or 10 3 or ii) reduce the laser power or laser power density by a factor of more than Degrees specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Reduce by a factor greater than It can be done.

[0516] In one embodiment of the present invention, the temperature gradient or average temperature gradient of the cooling step is in particular 1.001 , 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 can be reduced by a factor of more than , i) The concentration of magnetic nanoparticles, particularly magnetosomes, was increased to 1.001, 1.01, 1.1, 1.5, 2, 5, 10 , or 10 3 or ii) increase the laser power or laser power density by a factor greater than Degrees specifically 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 Increase by a factor exceeding This can be done with.

[0517] In one embodiment of the present invention, the magnitude of the temperature rise reached during the heating step DT HS And cooling system The magnitude of temperature drop achieved during the tapping, DT CS That is, 10 6 , 10 3 , 10 2 , 10, or less than 1% difference Here, this percentage is (DT HS -DT CS ) / DT HS or (DT CS -DT HS ) / DT CS to the absolute value of equal.

[0518] In yet another embodiment of the present invention, the maximum temperature gradient is reached at the beginning of the heating or cooling step. This is what we do.

[0519] The present invention also relates to a method of using magnetic nanoparticles, in particular magnetosomes, in which the dissociation step The group has developed a method to synthesize 100% of compounds from magnetic nanoparticles, particularly magnetosomes. -4 % higher dissociation I agree.

[0520] In one embodiment of the present invention, the dissociation step comprises dissociating the magnetic nanoparticles, in particular the magnetosomes, from the magnetic nanoparticles. The dissociation percentage of the compound is calculated as 10 -20 , 10 -10 , 10 -4 , 10 -1 , 1, 5, 10, or 50 Greater than %.

[0521] In one embodiment of the invention, the dissociation step is measured at any given time point during the dissociation step. of or in a body part containing magnetic nanoparticles, particularly magnetosomes, Gradient (DD / dt)t 1b which produces 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, or 10%. / sec Hear.

[0522] In one embodiment of the present invention, (DD / dt)t 1b is the time course of the percentage of dissociation that occurs during the dissociation step. It can be defined as the slope of the tangent to the

[0523] In one embodiment of the present invention, t 1b Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 100 When it increases by a factor exceeding (DD / dt)t 1b Specifically, 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or It decreases by a factor of over 100. This is because (DD / dt)t 1b is greater at the beginning of the dissociation step than at the end. This may mean that the percentage of dissociation measured at the beginning of the dissociation step is higher. The initial slope of the time course of is (DD / dt)t 1b It can mean that the maximum value of

[0524] In one embodiment of the present invention, the laser power, laser power density, laser intensity, and / or magnetic The concentration of the active nanoparticles, especially magnetosomes, was 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, or by a factor of more than 100, thereby allowing for different Measured at time (DD / dt)t 1bThis can reduce the variation between different values ​​of

[0525] In one embodiment of the present invention, Av[(DD / dt)t 1b ] fluctuations are 99, 90, 85, 75, 60, 50, 30, 20, 10 , 5, 2, 1, or 10 -1 % or less. This percentage is [(DD / dt)t 1b 1 -(DD / dt)t 1b2 ] / (D D / dt)t 1b can be equal to, where (DD / dt)t 1b1 and (DD / dt)t 1b2 is the dissociation step At two different times t 1b1 and t 1b2 is the slope in percent dissociation measured at .

[0526] In yet another embodiment of the present invention, the average gradient of the dissociation percentage measured during the dissociation step is , various times t 1b Measured at (DD / dt)t 1b This is the average value of t is used to 1b Various values ​​of are for similar periods or 10 -9 , 10 -6 , 10 -3 , 10 -1 , Specifically separated by periods greater than 1, 5, 10, 50, or 100 seconds. (DD / dt)t 1b The average value of Av[(DD / dt)t 1b ].

[0527] In one embodiment of the present invention, Av[(DD / dt)t 1b ] is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, or In one embodiment of the present invention, Av[(DD / dt)t 1b ] is 10 6 , 10 3 , 10 -3 , 5-1, 2 , 1, 5, or 10 -3 Lower than % / sec.

[0528] The present invention also relates to the use of magnetic nanoparticles, in particular magnetosomes, in which non-dissociated staphylococci are present. The technique results in less than 99% dissociation of compounds from magnetic nanoparticles, especially magnetosomes. I agree. In one embodiment of the present invention, the dissociation step involves the dissociation of magnetic nanoparticles, in particular magnetosomes, from It gives the percent dissociation of the compound, which can be 99.9, 99, 90, 80, 50, 40, 20, 10, 5, 2, or is less than 1%.

[0529] In one embodiment of the present invention, the non-dissociation step is measured at any given time during the non-dissociation step. The dissociation percentage of or in a body part containing magnetic nanoparticles, particularly magnetosomes, Rate gradient (DD / dt)t 2b which is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, or 10%. / sec. Very low.

[0530] In one embodiment of the present invention, (DD / dt)t 2b is the percentage of dissociation that occurs during the non-dissociation step over time It can be defined as the slope of the tangent to the change.

[0531] In yet another embodiment of the present invention, the average gradient of the dissociation percentage measured during the non-dissociation step. is a function of various times t 2b Measured at (DD / dt)t 2b This is the average value of t is used to 2b Various values ​​of are for similar periods or 10 -9 , 10 -6 , 10 -3 , 10 -1 , Specifically separated by periods greater than 1, 5, 10, 50, or 100 seconds. (DD / dt)t 2b The average value of Av[(DD / dt)t 2b ].

[0532] In one embodiment of the present invention, Av[(DD / dt)t 2b ] is 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, 2, 5, or Lower than 10% / sec.

[0533] In one embodiment of the present invention, Av[(DD / dt)t 2b ] is 10 6 , 10 3 , 10 -3 , 5-1, 2, 1, 5, or 1 0 -3 Lower than % / sec.

[0534] In one embodiment of the present invention, the dissociation percentage P reached during the dissociation step DS , and non-dissociated sta The fraction of dissociation achieved during the loop, P NDS The difference is 10 -6 , 10 -3 , 10 -2 , 10 -1 or more than 1% , this percentage is (P DS - P NDS ) / P DS or (P NDS - P DS ) / P NDS is equal to the absolute value of .

[0535] In one aspect of the invention, the present invention also relates to magnetic nanoparticles for use according to the invention, in particular magnetosomes or a method according to the invention, wherein the second step is to or in the presence of a substance or device that reduces the temperature of magnetic nanoparticles, particularly magnetosomes. There, i) the duration of the second step is more specific in the presence of such substance or device than in its absence; Short to ii) The difference between the maximum and minimum temperatures in the second step is less than in the absence of such substance or device. The effect is especially large in the presence of iii) the laser power irradiating the magnetic nanoparticles, particularly magnetosomes, during the first step is is particularly low in the presence of such substance or device than in its absence; iv) The concentration of magnetic nanoparticles, particularly magnetosomes, in body parts is important in determining whether such substances or is significantly lower when the device is present than when it is not. And also, v) The number of sequences performed during at least one session is limited by the number of sequences performed using such substances or devices. is especially greater in its presence than in its absence.

[0536] In one embodiment of the present invention, a substance or device that reduces the temperature of a body part or magnetic nanoparticles is provided. The device is selected from the following: i) to reduce the temperature of the body part or the magnetic nanoparticles; ii) cryogenic probes; iii) ice; iv) water; v) blood; and vi) In contact with or in close proximity to magnetic nanoparticles or body parts A material or device that is at a temperature lower than the temperature of the magnetic nanoparticles or body parts. This is measured prior to contact or proximity with the substance or device.

[0537] In one embodiment of the present invention, the duration of the second step is determined based on the presence of such substances or devices. Better to have it than not, especially if it is at least 0, 1, 1.1, 2, 5, 10 or 1 0 3 by a factor of, or at least 0, 10 -50 , 10 -1 , 1, 5, 10 or 10 3 Just a second shorter.

[0538] In one embodiment of the present invention, the difference between the maximum and minimum temperatures of the second step is determined by the temperature of such a material or is greater with the device than without it, especially at least 0, 1, 1.1, 2, 5 , 10 or 10 3 by a factor of, or at least 0, 10 -50 , 10 -1 , 1, 5, 10 or 10 3 ° Only C is larger.

[0539] In one embodiment of the present invention, the power of the laser irradiating the magnetic nanoparticles during the first step is In particular, it is less likely to occur in the presence of such substances or equipment than in their absence. Both are 0, 1, 1.1, 2, 5, 10 or 10 3 by a factor of, or at least 0, 10 -50 , 10 -1 , 1, 5, 10 or 10 3 °C smaller.

[0540] In one embodiment of the present invention, the concentration of magnetic nanoparticles contained in the body part during the first step is In particular, it is less likely to occur in the presence of such substances or equipment than in their absence. Both are 0, 1, 1.1, 2, 5, 10 or 10 3 In terms of coefficients of, or in particular cm 3 Per cm 2 Around, per cm, most specifically cm of body parts 3 Per cm 2 per cm, at least 0, 10 -50 , 10 -1 , 1, 5, 10 or 10 3 mg smaller.

[0541] In one embodiment of the present invention, the number of sequences performed during at least one session is particularly less likely in the presence of such substances or equipment than in their absence. At least 0, 1, 1.1, 2, 5, 10 or 10 3 by a factor of, or at least 0, 1 -50 , 5-1, 10 , 10, 2 or 10 3 Only the sequence is large.

[0542] In one aspect, the present invention also provides magnetic nanoparticles, particularly magnetic nanoparticles, for use according to the present invention. gnetosomes or a method according to the invention, wherein the first step comprises heating, The second step includes cooling, and the temperature of the first step and / or the cooling temperature of the second step are The degree is stable or within 99.9 of the duration of the first and / or second steps. %, in particular 50%, more particularly 10% or less and / or 10 5 Seconds, especially 10 3 Seconds, and especially 1 0 seconds or less, 10 5 , 10 3 , 10, 1 or 10 -1 It only fluctuates by ℃ or less.

[0543] In one embodiment of the present invention, the heating temperature of at least one first step is stable. A heating temperature is stable when: i) the fluctuations in heating temperature are less than 10 per hour, minute or second; 5 , 103 ii) the heating temperature remains constant; iii) especially in the first step At the end of the first step, the heating temperature reaches a steady state, or iv) the heating temperature reaches a steady state. is the temperature at the beginning or end of the

[0544] In one embodiment of the present invention, the heating temperature of at least one first step is unstable. Heat temperature is unstable when: i) the fluctuations in heating temperature are greater than 10% per hour, minute or second; - 10 , 10 -5 , 10 or more than 10 °C; ii) the heating temperature does not remain constant; iii) the heating The heating temperature is in a temperature range that provides a heating temperature gradient increase, or iv) the heating temperature is in the first step The temperature is between the middle of the two groups.

[0545] In one embodiment of the present invention, the heating temperature of the first step is at least one Periods 100, 99.9, 95, 90, 80, 70, 50, 20, 10, 1, 10 -1 , 10 -2 or 10 -5 Between % and This percentage is stable. SFS / D FS where D SFS Is warm The temperature is stable or varies less than 0.5°C or 0.5°C / The time lapse between the two, which varies by less than a second, is D FS is the duration of the first step.

[0546] In one embodiment of the present invention, the heating temperature of the first step is stable or does not vary per second. 0.5°C or less, or especially in the first step, 10 50 , 10 20 , 10 10 , 105 , 10 3 , 100, 10, 5, The temperature change is less than 0.5°C in less than 2 or 1 seconds.

[0547] In one embodiment of the present invention, the heating temperature of the first step is at least one Period 10 -5 , 10 -3 , 10 -1 , stable between 1, 5, 10, 50 or 75% or more.

[0548] In one embodiment of the present invention, the heating temperature of the first step is stable or does not vary per second. 0.5°C or less, or especially in the first step, 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , 100, 10, 5, The temperature change is less than 0.5°C in less than 2 or 1 seconds.

[0549] In the experimental example, 0.5 mg / mL of M-CMD was used at 2 W / cm 2 When exposed to a laser power of less than 10 seconds The temperature rise stabilizes or is less than 0.5°C (10 / 160 = 6% of the first step) over time. FIG. 1(a)). In some embodiments, this time lapse is longer if: i) the temperature is 0 is considered stable even if it changes by more than 0.5 °C; ii) there is a decrease in laser power or power density. and / or iii) the nanoparticle concentration is decreased. The elapsed time is shorter if: i) the temperature is considered stable with a change of less than 0.5 °C; ii) the laser power or power density is increased, and / or iii) the nanoparticle concentration is increased. .

[0550] In one embodiment of the present invention, the heating temperature of the first step is at least one Periods 100, 99.9, 95, 90, 80, 70, 50, 20, 10, 1, 10 -1 , 10 -2 or 10 -5 Between % and This percentage is stable. USFS / D FS where D USFS teeth, The temperature is stable or varies by more than 0.5 °C during the first step. is the lapse of time between which the fluctuation is greater than / sec, D FS is the duration of the first step.

[0551] In one embodiment of the present invention, the heating temperature of the first step is unstable or fluctuates every second. is 0.5°C or more, or especially in the first step, 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , 100, 10, 5 , the temperature change is 0.5°C or more for 2 or 1 seconds or less.

[0552] In one embodiment of the present invention, the heating temperature of the first step is at least one Period 10 -5 , 10 -3 , 10 -1 , unstable between 1, 5, 10, 50 or 75% or more.

[0553] In one embodiment of the present invention, the heating temperature of the first step is unstable or fluctuates every second. is 0.5°C or more, or especially in the first step, 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , 100, 10, 5 , the temperature change is 0.5°C or more for 2 or 1 seconds or less.

[0554] In the experimental example, 0.5 mg / mL of M-CMD was used at 2 W / cm 2 When exposed to a laser power of The temperature rise is unstable or greater than 0.5°C over time (150 / 160 = 1st step) 94%) (FIG. 1(a)). In some embodiments, this time lapse may be longer if: i) the temperature is considered stable with a change of less than 0.5 °C; ii) the laser power or power density is and / or iii) the nanoparticle concentration is increased. This time lapse is shorter if: i) the temperature change is more than 0.5 °C and is considered unstable; ii) the laser power or power density is reduced, and / or iii) the nanoparticle concentration is Decreases.

[0555] In one embodiment, the heating temperature in the first step is unstable over the course of the DUSFS. The elapsed time of D is the time during which the temperature is stable during the first step. SFS At least 1 of. 1, 1.5, 2, 5, 10, 10 3 or 10 5 It is double.

[0556] In one embodiment of the present invention, the cooling temperature of at least one second step is stable. The cooling temperature is stable when: i) the fluctuations in the cooling temperature are less than 10% per hour, minute or second; 5 , 10 3 ii) the cooling temperature remains constant; iii) especially in the second step At the end of the first step, the cooling temperature reaches a steady state, or iv) the cooling temperature reaches a steady state at the end of the second step. is the temperature at the beginning or end of the

[0557] In one embodiment of the present invention, the cooling temperature of at least one second step is stable. Cooling temperature is unstable when: i) the fluctuations in cooling temperature are greater than 10% per hour, minute or second; - 10 , 10 -5 , 10 or more than 10 °C; ii) the cooling temperature does not remain constant; iii) the cooling or iv) the cooling temperature is in a temperature range that provides an increase in the cooling temperature gradient in the first step. The temperature is between the middle of the two groups.

[0558] In one embodiment of the present invention, the cooling temperature of the second step is at least one second step. Periods 100, 99.9, 95, 90, 80, 70, 50, 20, 10, 1, 10 -1 , 10 -2 or 10 -5 Between % and This percentage is stable. SSS / D SS where D SSS Is warm The temperature is stable or fluctuates less than 0.5°C or 0.5°C / sec during the second step. The following variation is the passage of time between D SS is the period of the second step.

[0559] In one embodiment of the present invention, the cooling temperature in the second step is stable or does not vary per second. 0.5°C or less, or especially in the second step, 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , 100, 10, 5, The temperature change is less than 0.5°C in less than 2 or 1 seconds.

[0560] In one embodiment of the present invention, the cooling temperature of the second step is at least one period of the first step. Between 10 -5 , 10 -3 , 10 -1 , stable between 1, 5, 10, 50 or 75% or more. In one embodiment of the present invention, the cooling temperature in the second step is stable or does not vary per second. 0.5°C or less, or especially in the second step, 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , 100, 10, 5, The temperature change is less than 0.5°C in less than 2 or 1 seconds.

[0561] In the experimental example, 0.5 mg / mL of M-CMD was used at 2 W / cm 2 When exposed to a laser power of less than 10 seconds The temperature drop during the elapsed time is stable or less than 0.5°C (Figure 1(a)). In the form of i) the time elapsed, the equipment is used to cool the magnetic nanoparticles during the second step. or substances are used, ii) the maximum temperature of the first and / or second step is reduced, and and / or iii) shorter if the minimum temperature of the first and / or second steps is increased. It becomes.

[0562] In one embodiment of the present invention, the cooling temperature of the second step is at least one second step. Periods 100, 99.9, 95, 90, 80, 70, 50, 20, 10, 1, 10 -1 , 10 -2 or 10 -5 Between % and This percentage is D USSS / D SS where D USSS teeth , the temperature is unstable or fluctuates by more than 0.5 °C or between the second steps. is the lapse of time between which the fluctuation is greater than / sec, D SS is the period of the second step.

[0563] In one embodiment of the present invention, the cooling temperature of the second step is unstable or fluctuates every second. is 0.5°C or more, or especially in the second step, 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , 100, 10, 5 , the temperature change is 0.5°C or more for 2 or 1 seconds or less.

[0564] In one embodiment of the present invention, the cooling temperature of the second step is at least one period of the first step. Between 10 -5 , 10 -3 , 10 -1 , unstable between 1, 5, 10, 50 or 75% or more. In one embodiment of the present invention, the cooling temperature of the second step is unstable or fluctuates every second. is 0.5°C or more, or especially in the second step, 10 50 , 10 20 , 10 10 , 10 5 , 10 3 , 100, 10, 5 , the temperature change is 0.5°C or more for 2 or 1 seconds or less.

[0565] In the experimental example, 0.5 mg / mL of M-CMD was used at 2 W / cm 2 When exposed to a laser power of The temperature rise is unstable or greater than 0.5°C over time (180 / 190 = 1st step) 95%) (FIG. 1(a)). In some embodiments, this time lapse may be longer if: i) it is considered unstable even with a temperature change of less than 0.5 °C; ii) the magnetic nanoparticle concentration decreases and / or iii) the device or material is in contact with the magnetic field during the second step. It is used to cool the nanoparticles.

[0566] In some embodiments, a method for cooling the magnetic nanoparticles during the second step is used. The device or material may vary in how quickly it cools during the second step, depending on how it is used. In another embodiment, the temperature can be kept stable during the second step. It should be noted that this allows

[0567] In one embodiment, the cooling temperature in the second step is D USSS It is unstable over the elapsed time, The elapsed time is the time during which the temperature is stable during the second step. SSS At least 1.1 , 1.5, 2, 5, 10, 10 3 or 10 5 It is double.

[0568] In another aspect of the invention, the present invention provides magnetic nanoparticles for use according to the invention, preferentially In particular, magnetosomes or a method according to the invention, in which the first step and The second step is based on at least one property selected from the following group: It can be characterized as - The period is 10 -50 and 10 50 During the 10 minutes, especially -50 and 10 3 For a minute, more specific to 10 -50 and 60 minutes, and more specifically 10 -50 and 30 minutes, and more specifically, 0 -5and 30 minutes, and more specifically 10 -3 and 15 minutes, and more specifically 10 -1 Between 10 and 10 minutes, or even more specifically 10 -1 and 5 minutes, and - The interstep duration separating the first and second steps is i) 10 -10 and 10 20 During the 10 minutes, especially -5 and 10 5 During the minutes, especially 10 -5 and 10 minutes, more specifically 10 -5 and 1 minute, or ii) shorter than the duration of the first and / or second steps. stomach.

[0569] In one embodiment of the present invention, the inter-step duration is such that the temperature is preferably increased by 10 -5 , 10 -3 , 10 -1 or from a temperature rise of more than 1°C, preferably at least 10 per second -5 , 10 -3 , 10 -1 Or 1°C This is the time elapsed until the temperature drop exceeds the threshold.

[0570] In one embodiment of the present invention, the period between the first and second steps or the inter-step period The period must be at least 1.1, 2, 5, 10 or 10 longer than the period of the first or second step. 3 Coefficient of In the example experiment (Figure 1(a)), the temperature was increased from 44.5°C to 45°C at the end of the first stage. The elapsed time for raising the temperature was 5 seconds, and at the start of the second step the temperature was raised from 45°C. The elapsed time from the first step to 44.5°C is 5 seconds. The duration of the first and / or second step is 3 seconds. longer than 5 seconds. Within the temperature interval where the interstep duration is less than 44.5-45 °C, i.e. For example, if the temperature rises between 44.9-45°C, the inter-step duration may be shorter. The inter-tap duration occurs within a temperature interval greater than 44.5-45°C, i.e., between 44-45°C With this in mind, the inter-step duration can be longer.

[0571] In the example experiments (Table 2, 0.5 mg of M-CMD), the duration of the heating step is between 35 and 150 seconds. In some embodiments, the duration is determined by: i) increasing the laser power; ii) increasing the nanoparticle concentration; iii) increasing the minimum temperature of the heating step, and / or iv) increasing the maximum temperature of the heating step. In some embodiments, this duration can be reduced by lowering the high temperature. During the heating step, we tried to reduce the laser power, i) reduce the nanoparticle concentration, and iii) and / or iv) by increasing the maximum temperature of the heating step. It is possible.

[0572] In the example experiment (Table 2, 0.5 mg of M-CMD), the duration of the heating step is between 60 and 75 seconds. In some embodiments, this period may include the use of magnetic nanoparticles or devices that cool body parts or by using substances or by changing, increasing or decreasing the concentration of nanoparticles. In some other embodiments, this period can be reduced by decreasing by changing, decreasing or increasing nanoparticle concentrations or in body parts. By restricting blood circulation in the body or by contacting magnetic nanoparticles or body parts with magnetic nanoparticles This can be extended by limiting the heat exchange between the particle or body part and its environment. do.

[0573] In one embodiment of the present invention, the duration of the first step (D FS ) is the duration of the second step Time (D SS In some embodiments, D FS / D SS is 100, 50, 40, 10, 5 , 2, 1.5 or less than 1.1. In some embodiments, D FS / D SS is 10, 10, 10, 1, 5, 10, 50 or greater than 100.

[0574] In another aspect of the invention, the present invention provides magnetic nanoparticles for use according to the invention, preferentially In particular, magnetosomes or a method according to the invention, in which the first step and The first or second step is characterized by at least one property selected from the following group: To be assigned, - The period is 10 -50 and 10 50 During the 10 minutes, especially -50 and 10 3 More specifically, for 10 minutes -50 and 60 minutes, and more specifically 10 -50 and 30 minutes, and more specifically 10 -5 and 3 0 minutes, and more specifically 10 -3 and 15 minutes, and more specifically 10 -1 and 10 minutes Between, or even more specifically, 10 -1 and 5 minutes, and - The duration between two consecutive sequences, or the inter-sequence time, is 10 -10 and 10 2 0 For about 10 minutes, -5 and 105 For 10 minutes, more preferably -5 Between 10 and 20 minutes or less Furthermore, preferably 10 -5 and 1 minute duration, and - The duration of at least one sequence is longer than the duration of at least one step. , preferentially at least 0, 1.1, 1.5 or 2 times longer;

[0575] In one embodiment of the present invention, at least one sequence or at least one first The duration of the step, or at least one of the second steps, is 10 -100 , 10 -50 , 1 0 -10 , 10 -5 , 10 -1 , 1, 5, 10 or longer than 100.

[0576] In one embodiment of the present invention, at least 10 sequences or at least one first The duration of the step, or at least one of the second steps, is 10 100 , 10 50 , 10 2 0 , 10 10 , 10 5 , shorter than 1, 5, 2 or 10.

[0577] In the example experiments, the duration of the sequences is between 95 and 225 seconds (Table 2, 0.5 mg MC In some embodiments, the duration of the sequence is: i) increasing the laser power; ii) increasing the nanoparticle concentration; iii) increasing the maximum concentration reached during the first and / or second steps. reducing the high temperature; iv) increasing the minimum temperature reached during the first and / or second steps. and / or v) using a device or substance to disperse the magnetic nanoparticles or In some embodiments, the duration of the sequence may be reduced by cooling the body part. The duration of the laser beam is increased by: i) decreasing the laser power; ii) decreasing the nanoparticle concentration; and iii) decreasing the first and / or increasing the maximum temperature reached during the first and / or second steps; iv) This can be extended by lowering the minimum temperature reached during the step.

[0578] In one embodiment of the present invention, the duration of the sequence or of the first and / or second steps The time is long enough to allow the immune system to be stimulated. It is typically about 1 second. is preferentially longer than the duration of the significantly shorter laser pulse. In one embodiment of the present invention, the duration of the sequence or the first and / or second steps is , short enough to avoid burning body parts or inducing side effects on body parts.

[0579] In one embodiment of the invention, the duration of at least one sequence is at least one The duration of the first step or at least one of the second steps is preferentially less than that of the first step or at least one of the second steps. At least 0, 0.5, 1, 1.1, 1.5, 2, 5, 10 or 10 3 Twice as long.

[0580] In one embodiment of the present invention, the time between two different sequences, also called the inter-sequence duration, The duration between steps is at least 0, 1, and preferably at least one inter-step duration. , 1.1, 1.5, 2, 5, 10 or 10 3 Twice as long.

[0581] In one embodiment of the present invention, the time between two different sequences, also called the inter-sequence duration, The duration between steps is at least 0, 1, and preferably at least one inter-step duration. , 1.1, 1.5, 2, 5, 10 or 10 3 Twice as long.

[0582] In another aspect of the invention, the present invention provides magnetic nanoparticles for use according to the invention, preferentially In particular, magnetosomes or a method according to the invention, in which the first step and The first or second step is characterized by at least one property selected from the following group: To be assigned, - Each treatment session is 10 -50 and 10 50 During the minutes, especially 10 -50 and 10 3 For a minute, more specific 10 to -50 and 60 minutes, and more specifically 10 -50 and 30 minutes, and more specifically, 0 -5 and 30 minutes, and more specifically 10 -3 and 15 minutes, 10 -1 and for 10 minutes, More specifically, 10 -1 and 5 minutes, and between the two treatment sessions, 10 -10 and 10 20 During the minutes, especially 10 -5 and 10 5 For 10 minutes, more specifically -5 and for 10 minutes, more specifically 10 -5 and an intersession period of 1 min. - At least one session is preferred to the duration of at least one sequence or at least 1.1 times longer, and - preferentially over the duration of at least one sequence between two treatment sessions There is at least one session interval having a duration that is at least 1.1 times longer.

[0583] In one embodiment of the present invention, the duration of at least one session or session interval is 10 times smaller than at least one sequence or sequence interval. -100 , 10 -50 , 10 -10 , 10 -5 , 10 -1 , 1, 5, 10, 10 3 or 10 5 It's just a minute longer.

[0584] In one embodiment of the present invention, the duration of at least one session or session interval is: At least one sequence or sequence interval is preferentially at least 0, 1, 5, 1.5, 2, 10, 3 or 10 5 It is longer by a factor of .

[0585] In one embodiment of the present invention, the duration of at least one session interval is sequence, one step, one sequence interval, one session. At least 0, 1, 1.1, 2, 5, 10, 10 3 or by at least 10 -50 , 10 -3 , 0, 1, 10, 100 or 10 3 It's just a minute longer.

[0586] In one embodiment of the present invention, at least 10 sessions or inter-session periods is 10 100 , 10 50 , 10 10 , 10 5 , 10 3 , 10 2 , 50, 20, 10, 5, 2 or less than 1 minute.

[0587] In the example experiment, the session duration was 6 min (Figs. 2 and 3), and it contained 22 sequences (Fig. 2(c)) and 1 9 sequence (FIG. 3(c)). In some embodiments, for example, each set The duration of the session is extended to increase the number of sequences in the session. In an embodiment, the duration of a session may be shortened, for example to reduce the number of sequences in each session. The time is shortened.

[0588] In one aspect of the invention, the present invention provides magnetic nanoparticles for use according to the invention, preferentially The present invention relates to magnetosomes or to a method according to the present invention, in which in the first step and In the second step, the magnetic nanoparticles are preferentially transported to the magnetosomes at least one of the compounds. When the dissociation of the substance reaches a given rate, and / or at a given temperature of the first step GT FS and / or the given temperature GT of the second step SS When it reaches , it ends, where GT SS and G.T. FS is characterized by at least one property selected from the group consisting of: Can be done, -GT SS GT FS is higher than -(GT SS -GT FS ) is between 0 and 10 5 ℃ between 10 -5 and 10 5 ℃ between 10 -3 and 10 3 ℃ between 10 -1 and 10 2 ℃ between 10 -1 Between 10 and 50 degrees Celsius -1 Between 10 and 20 degrees Celsius -1 Between and 10°C, or 10 -1 and 5 °C, -GT SS and / or GT FS is -273 and 10 3 °C, preferably between -100 and 10 3 Between °C , more particularly between 0 and 100°C, most particularly between 30 and 70°C, most particularly between 30 and 60° C., most preferably between 37 and 55° C., -GT SS within the range of temperatures reached during hyperthermia, i.e. preferentially between 37 and 70°C. C., most preferentially within the range of 37 to 60.degree. -GT FS is preferably at i) cryogenic temperature or -40°C, ii) 0°C or ice formation temperature, or iii) at physiological temperature or 37°C; and -GT SS and G.T. FS is preferably less than or equal to: i) the boiling point of water or tissue; or 100°C, or ii) the ablation temperature or 70°C. GT SS and G.T. FS Especially at 37°C or 10°C above physiological temperature 5 , 10 3 , 10, 5, 2 or within 1°C.

[0589] In one embodiment, the temperature of the ablation temperature is preferably such that the immune system or apoptosis is preferentially regulated. In particular, the removal or elimination of body parts or pathological cells by burning body parts. is the temperature at which destruction occurs.

[0590] In one embodiment of the present invention, the first step is performed by turning off the laser, or Finish by reducing the laser power.

[0591] In one embodiment of the present invention, the second step is performed by turning on a laser, or Finish by increasing the laser power.

[0592] In one embodiment of the present invention, the given temperature is the temperature to be reached or the temperature to be reached by the first or second step. In some embodiments, it is the temperature reached at the end of the first step. Corresponds to the maximum temperature or the minimum temperature of the second step.

[0593] In one embodiment of the present invention, a given percentage of dissociation is determined based on the temperature to be reached or the first or second temperature. The percentage of dissociation reached at the end of the second step. corresponds to the highest percent dissociation in the first step or the lowest percent dissociation in the second step.

[0594] In one embodiment of the present invention, GT SS and G.T. FS are -273, -100, -50, -10, 0, 5, 10 , 20, 37, 40, 41, 45, 50 or 60 higher than 0°C.

[0595] In one embodiment of the present invention, GT SS and G.T. FS is 10 20 , 10 10 , 10 5 , 10 3 , 100, 90 , 80, 70, 60, 55, 50, 45, 43, 42, 41, 40, 39, 38, 37, 36, 35, 30, 20, 10 or Below 0°C.

[0596] In the experimental example, GT FS Between about 45 and about 50°C, GT SS is approximately 37°C (Fig. 1, Fig. 2(c), Fig. 3(c) ). GT FSis more suitable when you want to heat body parts or magnetic nanoparticles to higher temperatures. It can be expensive. GT FS would like to heat body parts or magnetic nanoparticles at lower temperatures. It may be lower at times.

[0597] In one aspect of the invention, the present invention also relates to magnetic nanoparticles for use, in particular magnetospheric nanoparticles. wherein the first and second steps are terminated when a given percentage of dissociation is achieved. or at a predetermined temperature, preferably at least one first step or at least one second step About 2 steps - 273 and 10 5 ° C., more preferably at least one first step 0 and 10 for each step and at least one second step 3 ℃ or the most Preferably for at least one first step or at least one second step Between 0 and 70 degrees Celsius.

[0598] In one embodiment of the present invention, the first and / or second step may be -273, -270, -150, -100, - 50, -20, 0, 5, 10, 15, 20, 37, 40, 41, 43, 45, 50, 55, 60, 70, 80, 90, 100, 200 , 500, or 1000 °C.

[0599] In another embodiment of the invention, the first and / or second step is -273, -270, -150, -10 0, -50, -20, 0, 5, 10, 15, 20, 37, 40, 41, 43, 45, 50, 55, 60, 70, 80, 90, 100, It ends when a temperature below 200, 500, or 1000 °C is reached.

[0600] In one embodiment of the present invention, the first and / or second step is -20 , 10 -10 , 10 -5 , 10 -3 , 1 0 -1 , 1, 5, 10, 10 3 , 10 5 , 10 10 , or 10 20 The end point is reached when a dissociation percentage higher than 10% is reached. Complete.

[0601] In one embodiment of the present invention, the first and / or second step is -20 , 10 -10 , 10 -5 , 10 -3 , 1 0 -1 , 1, 5, 10, 10 3 , 10 5 , 10 10 , or 10 20 The end point is reached when the dissociation percentage is less than 10%. Complete.

[0602] In one embodiment of the present invention, the first and / or second step comprises: i) a laser or lasers Switch off or stop the power or laser intensity or laser equipment or laser device ii) preferentially changing the laser output or laser intensity between the first step and the second step; Between 1.001, 1.01, 1.1, 1.5, 2, 5, 10, 50, 10 preferentially 2 , 10 3 , 10 6 , or 10 9 Yo The process ends by decreasing it by a factor greater than

[0603] The present invention also relates to magnetic nanoparticles, in particular magnetosomes, for use in which a magnetic The concentration of nanoparticles, in particular magnetosomes, and / or the first and / or second steps The duration of the tap, and / or the laser power or laser power density or laser intensity, The temperature and rate of dissociation occurring during the first and / or second steps may vary or gradient as desired. is adjusted to achieve the desired distribution.

[0604] In one embodiment of the present invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is preferentially increased in the body. In parts, 1 cm of body parts 3 Magnetic nanoparticles, especially magnetosomes, are 10 -9 , 10 -6 , 10 -3 , 10 -2 , 10 -1 , 1, 10, 100, or 10 3 The concentration is adjusted to a value of 100 mg or more. Magnetic nanoparticles, especially magnetosomes, localize body parts, preferably on the nanometer scale. This allows for localized heating.

[0605] In the experimental example, for M-CMD, an increase in concentration from 0.5 to 1 mg per mL resulted in a 1.6 This results in an increase in the average temperature gradient during the heating step by a factor included between 2.2. Therefore, the concentrations of magnetic nanoparticles, especially magnetosomes, were preferentially set to 1.001, 1.01, 1.1, 2, 5, 10, or 10 3 and can be advantageously reduced during the heating step by a factor of more than Preferably 1.001, 1.01, 1.1, 2, 5, 10, or 10 3 The average temperature gradient decreases by a factor of more than reaches.

[0606] In another embodiment of the invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is preferably 1.00 1, 1.01, 1.1, 2, 5, 10, or 10 3 can be increased by a factor of more than During the heating step, preferably 1.001, 1.01, 1.1, 2, 5, 10, or 10 3 By a factor exceeding An increasing average temperature gradient is reached.

[0607] In the experimental example, for M-CMD, an increase in concentration from 0.5 to 1 mg per mL resulted in a 1.1 This results in an increase in the average temperature gradient during the heating step by a factor comprised between 1.3.

[0608] In another embodiment of the invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is preferably 1.00 1, 1.01, 1.1, 2, 5, 10, or 10 3 can be reduced by a factor of more than During the cooling step, preferably 1.001, 1.01, 1.1, 2, 5, 10, or 10 3 By a factor exceeding An increased average temperature gradient is reached.

[0609] In another embodiment of the invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is preferably 1.00 1, 1.01, 1.1, 2, 5, 10, or 10 3 It is possible to increase the z factor by more than Preferably, the temperature is 1.001, 1.01, 1.1, 2, 5, 10, or 10°C during the cooling step. 3 Coefficient exceeding A reduced average temperature gradient is reached at

[0610] In one embodiment of the present invention, the concentration of sufficiently large magnetic nanoparticles, particularly magnetosomes, is sufficient The absorption rate, SAR, of extremely large magnetic nanoparticles, especially magnetosomes M You are asked to reach . This may happen.

[0611] In one embodiment of the present invention, the SAR MThe magnetic nanoparticles, especially magnetosomes, are 10 -2 0 , 10 -10 , 10 -5 , 10 -2 , 10 -1 , 1, 5, 10, 10 2 , or 10 3 W, or magnetic nanoparticles, especially Watts per gram of iron oxide in magnetosomes, or magnetic nanoparticles, especially magnets It can be higher than the watts per gram of iron contained in the netosome.

[0612] In yet another embodiment of the present invention, a SAR M The magnetosphere is composed of magnetic nanoparticles with different concentrations. Between the 5 , 500, 90, 70, 50, 25, 10, 5, or 2 percent change or decrease or increase This percentage is the SAR MC2 -SAR MC1 / SAR MC1 where SAR MC1 and S AR MC2 are the concentrations of magnetic nanoparticles, specifically magnetosomes, for the two different concentrations.

[0613] In one embodiment of the present invention, this situation occurs when the concentration of magnetic nanoparticles, in particular magnetosomes, is Body Parts 10 -6 and 10 6 Between 10 -5 and 10 5 , 10 -3 and 10 3 , or 10 -2 and 10 2 mL between or mg or cm 3 In some other embodiments, this occurs when The situation is that the concentration of magnetic nanoparticles, especially magnetosomes, in the body parts is 1000, 100, 10, 1, 0.1 , or mg or cm per 0.01 mL 3 This can occur when the dose is less than 1 mg per 100 mg.

[0614] In some other embodiments, this situation occurs when the concentration of magnetic nanoparticles, particularly magnetosomes, is , mg per 1000, 100, 10, 1, 0.1, or 0.01 mL or mg per cm3 of body part or more This can occur when:

[0615] In one embodiment of the present invention, the SAR M is contained in, mixed with, or inserted into a body part. This is the specific absorption rate of magnetic nanoparticles, especially magnetosomes, which is expressed in units of power such as watts. Divide the mass unit into grams, or convert the power unit into cm, cm 2 , or cm 3 The length of It can be expressed as a surface area or a volume unit. M Preferentially, magnetic nanoparticles It is preferentially measured in the presence of particles, especially magnetosomes, and under application of radiation which causes a temperature increase. In one embodiment, the radiation is preferentially 10 -9 , 10 -5 , 10 -3 , 10 -1 , 1, 10, or 10 3 W or W / cm or W / cm 2 or W / cm 3 Higher power or power density It may be a laser.

[0616] In some other embodiments of the invention, the radiation is preferably 10 -9 , 10 -5 , 10 -3 , 10 -1 , 1, 10, or 10 3 W / cm or W / cm 2 or W / cm3 Higher power or power density than degree, preferably 10 -6 , 10 -3 , 10 -1 , 1, 10, 10 3 , or 10 6 Sound waves with frequencies higher than MHz It is.

[0617] In some other embodiments of the invention, the radiation is preferably 10 -9 , 10 -6 , 10 -3 , 10 - 1 , 1, 10, 10 3 , or 10 6 of power higher than 10 mT, preferably -9 , 10 -6 , 10 -3 , 1, 1 0 3 , 10 6 , or 10 9 SAR is an alternating magnetic field with a frequency higher than kHz. M is an adiabatic or superior The measurement is performed primarily under conditions that minimize heat exchange between: i) the magnetic nanoparticles; The parts of the body parts that contain magnetosomes and the parts of the body parts that do not contain magnetic nanoparticles were i.e. an area outside the body part that contains magnetic nanoparticles, in particular magnetosomes, or ii) a magnetic A container or tube containing nanoparticles, particularly magnetosomes, and the container or tube The heat exchanger is designed to reduce the temperature by 75, 60, 50, 25, 10, 5, 2, 1, or 0.1 degrees Celsius. It is minimized when

[0618] In one embodiment of the present invention, the SAR M The magnetic field is generated by the body parts, the medium, the water, magnetic nanoparticles, especially magnetos The initial gradient of temperature change with time for the tissue, including the mass (T / t) (M) mosquito However, the magnetic nanoparticles, especially magnetosomes, do not affect the body parts, media, water, and tissues over time. The initial gradient of the temperature change (T / t) (WM) proportional to the difference between (T / t) (M) and (T / t) (WM) is given priority Estimated in °C / sec. SAR M is preferentially estimated using the following formula: M =  rea l [(T / t) (M) -(T / t) (WM) ], where  real teeth In one embodiment, the SAR M =  real [(T / t) (M) -( T / t) (WM) ]C v / C mag where Cv is preferentially the body part, is the specific heat capacity of the medium containing the tissue, water, nanoparticles, and in particular magnetosomes, and C mag teeth, The concentration of magnetic nanoparticles, particularly magnetosomes, preferentially contained in body parts, or the concentration of magnetic nanoparticles The quantity or number of magnetosomes, in particular magnetosomes, is

[0619] In one embodiment of the present invention, the SAR M is (T / t) (M) For (T / t) (WM) The specific absorption rate of magnetic nanoparticles, especially magnetosomes, estimated without subtracting This is (T / t). (WM) is small, especially 10 -9 , 10 -6 , 10 -3 , 10 -1 , 1, It may be less than 10, or 20 °C / sec.

[0620] In one embodiment of the present invention, the SAR M The magnetic field is influenced by magnetic nanoparticles, especially magnetosomes, contained in body parts. The initial gradient of the temperature change over time of the system (T / t) (M) is proportional to, which is preferentially is estimated in °C / sec and is preferentially derived as follows: SAR M =  real [(T / ɧ 40;t) (M) -(T / t) (WM) ], where  real is the proportionality coefficient.

[0621] In another embodiment of the invention, the SAR M =(T / t)(M)-(T / t ) (WM) Cv / C mag where Cv is preferentially the concentration of body parts, tissues, water, nanoparticles, especially is the specific heat capacity of the medium containing magnetosomes, and C mag is preferentially included in body parts The concentration of magnetic nanoparticles, particularly magnetosomes, contained in the is the amount or number of.

[0622] In yet another embodiment of the present invention, magnetic nanoparticles, in particular magnetosomes, or SAR lase r The SAR measured by shining a laser on the body parts specified in AMF Magnetic nanoparticles, specifically magnetosomes, are designated as In one embodiment of the present invention, the SAR laser is SAR AMF and at least 10 -9 , 10 -7 , 10 -5 , 10 -3 , 10 -1 , 1, 10, 103 , 10 5 , 10 7 , or 10 9 %, and this percentage is (SAR laser - S.A.R. AMF ) / SAR laser Etc. This percentage is preferentially determined for a given concentration of magnetic nanoparticles, particularly magnetosomes. will be done.

[0623] In one embodiment of the present invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is mL of magnetosomes or 10 -1 Between 10 and 10 mg per day -9 and 10 9 , 10 -7 and 10 7 , 10 -5 and 10 5 , 10 -3 and 10 3 Between or 10 -1 Between and 10. In one embodiment of the present invention, The concentration of magnetic nanoparticles, especially magnetosomes, is preferentially within 1 cm of the body part. -9 Magnetic field Magnetosomes, especially magnetosomes, are 10 9 , 10 7 , 10 5 , 10 3 , 10 1 , 10, 10, 10, or 10 3 mg or less It is.

[0624] In one embodiment of the present invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is preferentially increased in the body. 1cm of product -9 Magnetic nanoparticles, especially magnetosomes, are 10 9 , 10 7 , 10 5 , 10 3 , 10 1 , 10, 1 0, 10, or 103 mg or more.

[0625] In one embodiment of the present invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is preferentially increased in the body. In parts, 1 cm of body parts -3 or 1 mg of magnetic nanoparticles, especially magnetosomes 0 9 , 10 6 , 10 3 , 10 2 , 10 -1 , 1, 10, -1, or 10 3 It is adjusted to a value of less than mg. Low enough The toxicity of magnetic nanoparticles, especially magnetosomes, was ameliorated by the high concentration of magnetic nanoparticles, especially magnetosomes. To be sought or sought in order to avoid.

[0626] In another embodiment of the present invention, a too low concentration of magnetic nanoparticles, particularly magnetosomes, is not sufficient. Local heating is not possible, and in some cases macroscopic heating, i.e., 1, 10, 10 3 , 10 6 ,or 10 9 This can result in heating on a scale larger than nm. Magnetic nanoparticles, particularly magnetosomes, of this order are avoided.

[0627] In one embodiment of the present invention, the localized heating or localized temperature increase refers to heating or increasing the temperature on a local scale. is defined as the heating that can be measured locally or on a local scale, with the local scale being 10 9 , 10 7 , 10 5 , 10 3 , 10, 1, 10 -1 , or 10 -3 Sub-nm, or even nanometer scale or the size of a single magnetic nanoparticle, particularly a magnetosome, or the size of an aggregate of magnetic particles. Refers to a scale close to

[0628] In one embodiment of the present invention, the localized heating or localized temperature increase refers to heating or increasing the temperature on a local scale. is defined as the heating that can be measured locally or on a local scale, with the local scale being 10 9 , 10 7 , 10 5 , 10 3 , 10, 1, 10 -1 , or 10 -3 nm or larger, or nanometer scale The size of a single magnetic nanoparticle, particularly a magnetosome, or an aggregate of magnetic bodies It refers to a scale that transcends size.

[0629] In one embodiment of the present invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is preferably 1.001 , 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 , or 10 6 By a factor of more than , or preferentially 10 per cm3 of body part -6 , 10 -3 , 10 -1 , 1, 5, or 10 mg of magnetic nanoparticles, especially magnets The temperature gradient, average temperature gradient, or or temperature fluctuation, preferentially 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 , or 10 6 of in multiples exceeding 10, or preferentially -6 , 10 -3 , 10 -1 , 1, 5, 10, or 10 3 ℃ and above can be increased.

[0630] In one embodiment of the present invention, the concentration of magnetic nanoparticles, in particular magnetosomes, is preferentially 1.001 , 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 , or 10 6 By a factor of more than , or preferentially 10 per cm3 of body part -6 , 10 -3 , 10 -1 , 1, 5, or 10 mg or more of magnetic nanoparticles The percentage of dissociation during the first and / or second steps by magnetosomes was determined by Specifically, 1.001, 1.01, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 , or 10 6 and is preferentially 10 -6 , 10 -3 , 10 -1 , increased by 1, 5, 10, 25, 50, 75, 80, or 90% or more. It is possible to do so.

[0631] In another embodiment of the present invention, t 1b and / or t 2b , preferably 1.001, 1.01, 1.1, 1. 2, 1.5, 2, 5, 10, 10 3 , or 10 6 or preferably at a magnification of 10 20 , 10 10 , 10 5 , 10 3 , 10 2 , 50, 10, or 1 second or less will cause the first and / or second steps The slope of the percentage of dissociation occurring during the loop, the average percentage of dissociation, is preferably set to 1.001, 1.0 1, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 , or 10 6 by a factor of more than 10 or preferentially -6 , 1 0 -3 , 10 -1 , 1, 5, 10, 25, 10, 3, 80, or even 90% or more.

[0632] In another embodiment of the present invention, t 1b and / or t 2b , preferably 1.001, 1.01, 1.1, 1. 2, 1.5, 2, 5, 10, 10 3 , or 10 6 or preferably at a magnification of 10 20 , 10 10 , 10 5 , 10 3 , 10 2 , 50, 10, or 1 second or less will cause the first and / or second steps The slope of the percentage of dissociation occurring during the loop, the average percentage of dissociation, is preferably set to 1.001, 1.0 1, 1.1, 1.2, 1.5, 2, 5, 10, 10 3 , or 10 6 by a factor of more than 10 or preferentially -6 , 1 0 -3 , 10 -1 , 1, 5, 10, 25, 50, 75, 80, or even 90% or more.

[0633] In one embodiment of the present invention, the first step is performed at the highest temperature, i.e. by laser irradiation. Preferentially higher than the temperature reached before or without irradiation, preferentially 10 -3 , 1, 5, 10, or to reach a temperature 50 °C or higher.

[0634] In some other embodiments of the invention, the first step is to measure the maximum percentage dissociation, i.e. Preferentially, the percentage of dissociation reached before or without irradiation with laser light is There are 10 -3 , 10 -1 , to reach a percentage of dissociation that is 1, 10, or 25% higher. It is possible.

[0635] In one embodiment of the present invention, the first step is performed by determining the maximum amount or concentration of radical species, i.e. Preferentially the amount or concentration of radical species that arrives before or without irradiation by laser radiation , cm of body parts 3 per mg of magnetic nanoparticles, or at least 10 -6 , 10 -3 , 1, 10 , 10 3 or 10 6 This can be done to reach amounts or concentrations of radical species in the range of 1 μM or more.

[0636] In one embodiment of the present invention, the temperature of the first step, preferentially the maximum temperature of the first step or is the minimum temperature, and the maximum temperature that we want to reach in the first step is 273, -150, -100. , -50, -20, -10, -5, -3, -1, 5, 10, 50, 10 2 , or 10 3 Higher than ℃. In one embodiment of the present invention, the dissociation percentage of the first step, preferentially the maximum of the first step, or the lowest dissociation percentage, and most preferentially the highest dissociation percentage that is desired to be reached in the first step. Higher than 90, 80, 70, 50, 25, 10, 5, 2, or 1 percent.

[0637] In one embodiment of the present invention, the amount or concentration of radical species in the first step, preferentially the first step Maximum or minimum fraction of radical species in each step, most preferentially reached in the first step The maximum amount or concentration of radical species desired is preferably 1 cm 3 Around or Magnetic nanoparticles per mg -50 , 10 -10 , 10- 5 , 10 -2 , 1, 5, or 10 μM of radical species. High.

[0638] In one embodiment of the present invention, the temperature of the first step, preferentially the maximum temperature of the first step or is the minimum temperature, and the maximum temperature you want to reach in the first step is -273, -150, -100. , -50, -20, -10, -5, -3, -1, 5, 10, 50, 10 2 , or 10 3 Lower than °C. In one embodiment of the present invention, the dissociation percentage of the first step, preferentially the maximum of the first step, or the lowest dissociation percentage, and most preferentially the highest dissociation percentage that is desired to be reached in the first step. lower than 90, 80, 70, 50, 25, 10, 5, 2, or 1 percent.

[0639] In one embodiment of the present invention, the amount or concentration of radical species in the first step, preferentially the first step Maximum or minimum fraction of radical species in each step, most preferentially reached in the first step The maximum amount or concentration of radical species desired is preferably 1 cm 3 Around or Magnetic nanoparticles per mg 50 , 10 10 , 10- 5 , 10 2 , from 1, 5, or 10 μM radical species. small.

[0640] In one embodiment of the present invention, the second step is carried out at the lowest temperature, i.e., Preferentially lower than the maximum temperature reached, preferentially 10 -3 , 1, 5, 10, or 50 degrees Celsius or higher The process can be carried out to reach a lower temperature.

[0641] In some other embodiments of the invention, the second step is to determine the minimum dissociation percentage, i.e., the preferred Prior to this, the dissociation percentage reached in the first step is increased by 10 -3 , 10 -1 , 1, 10, or It can be performed to reach a percentage of dissociation as low as 25% or more. In one embodiment of the present invention, the second step is performed by determining the maximum amount or concentration of radical species, i.e. Preferentially the amount or concentration of radical species that arrives before or without irradiation by laser radiation , cm of body parts 3 per mg of magnetic nanoparticles, or at least 10 -6 , 10 -3 , 1, 10 , 10 3 or 10 6 can be performed to reach amounts or concentrations of radical species as low as μM .

[0642] In one embodiment of the present invention, the temperature of the second step, preferentially the maximum temperature of the second step or is the minimum temperature. The minimum temperatures that we want to reach in the first step are -273, -150, and -100. , -50, -20, -10, -5, -3, -1, 5, 10, 50, 10 2 , or 10 3 Higher than ℃. In one embodiment of the present invention, the dissociation percentage of the second step, preferentially the maximum of the second step, or the minimum dissociation percentage, and most preferentially the minimum dissociation percentage that is to be reached in the first step is Higher than 90, 80, 70, 50, 25, 10, 5, 2, or 1 percent.

[0643] In one embodiment of the present invention, the amount or concentration of radical species in the second step, preferentially the second step Maximum or minimum fraction of radical species in the first step, most preferentially reached in the second step The maximum amount or concentration of radical species desired is preferably 1 cm 3 Around or Magnetic nanoparticles per mg -50 , 10 -10 , 10- 5 , 10 -2 , 1, 5, or 10 μM of radical species. High.

[0644] In one embodiment of the present invention, the temperature of the second step, preferentially the maximum temperature of the second step or is the minimum temperature, and the minimum temperatures we want to reach in the second step are -273, -150, and -100. , -50, -20, -10, -5, -3, -1, 5, 10, 50, 10 2 , or 10 3 Lower than °C. In one embodiment of the present invention, the dissociation percentage of the second step, preferentially the maximum of the second step, or the lowest dissociation percentage, and most preferentially the highest dissociation percentage that is desired to be reached in the second step. lower than 90, 80, 70, 50, 25, 10, 5, 2, or 1 percent.

[0645] In one embodiment of the present invention, the amount or concentration of radical species in the second step, preferentially the second step Maximum or minimum fraction of radical species in each step, most preferentially reached in the first step The maximum amount or concentration of radical species desired is preferably 1 cm 3 Around or Magnetic nanoparticles per mg 50 , 10 10 , 10- 5 , 10 2 , from 1, 5, or 10 μM radical species. low.

[0646] In one embodiment of the present invention, the minimum temperature desired to be reached in the second step is the minimum temperature desired to be reached in the first step. At least 1, 5, 10, 50, 100, 10 above the highest temperature you want to reach 3 , or 10 5 ℃ low stomach.

[0647] In one embodiment of the present invention, the dissociation percentage desired to be reached in the second step is At least 1, 5, 10, 50, 75, 80, or 90% below the percentage of dissociation you want to achieve in the loop. low.

[0648] In one embodiment of the present invention, the temperature of the second step, preferentially the maximum temperature of the second step or is the minimum temperature, and the maximum temperatures we want to reach in the second step are -273, -150, and -100. , -50, -20, -10, -5, -3, -1, 5, 10, 50, 10 2 , or 10 3 Lower than °C. In one embodiment of the present invention, the dissociation percentage desired to be reached in the second step is At least 1, 5, 10, 50, 75, 80, or 90% below the percentage of dissociation you want to achieve in the loop. low.

[0649] In still other embodiments of the present invention, the method includes the steps of: The desired maximum or minimum temperature or rate of dissociation is reached during the first or second step. The maximum or minimum temperature or rate of dissociation achieved may be the same as the maximum or minimum temperature or rate of dissociation achieved.

[0650] In still other embodiments of the present invention, the method includes the steps of: The desired maximum or minimum temperature or rate of dissociation is reached during the first or second step. The highest or lowest temperature or percent dissociation and 1.001, 1.01, 1.1, 1.5, 2, 5, 10, or 10 3 They may differ only by a factor of 1 or more.

[0651] In yet another embodiment of the present invention, the absolute value of the temperature variation or gradient occurring in the first step is determined by the absolute value of the temperature fluctuation or gradient occurring in the second stage, in increments of 1.1, 1.2, 1.5, 2, 5, 10, or or 10 3 The above coefficients do not differ.

[0652] In yet another embodiment of the present invention, the absolute value of the temperature variation or gradient occurring in the first step is determined by the absolute value of the temperature fluctuation or gradient occurring in the second stage, in increments of 1.1, 1.2, 1.5, 2, 5, 10, or or 10 3 It differs by the above coefficients.

[0653] The present invention also relates to magnetic nanoparticles, in particular magnetosomes, for use, in which first and The duration of the first and second steps is 10 -9 Seconds to 10 3 Between times. In one embodiment of the present invention, the duration of the first and / or second step is 10 -20 seconds and 10 20 For 10 hours -9 Seconds and 10s 10 For hours, 10 -3 Between seconds and hours, 10 -3 Seconds and 10s 3 Between seconds , 10 -2 Seconds and 10s 3 For 10 seconds -1 Between 1 and 10 seconds, 1 and 10 3 Between seconds, 1 and 10 2 For seconds, Or between 1 second and 50 seconds.

[0654] The present invention also relates to magnetic nanoparticles, in particular magnetosomes, for use, wherein the first and The ratio of the duration of the first and second steps is 10 -20 From 10 20 It is between. In one embodiment of the present invention, the ratio between the duration of the first step and the duration of the second step is: 10-20 and 10 20 Between 10 -10 and 10 10 , 10 -5 and 10 5 , 10 -3 and 10 3 , 10 -1 and 10, 0.5 and 5, or between 0.5 and 2.

[0655] In one aspect of the invention, the present invention provides magnetic nanoparticles, in particular magnetrons, for use according to the invention. The method according to the invention relates to a method for the preparation of a medicament ... i) magnetic nanoparticles, in particular magneto The reduction of magnetosomes and the diffusion of magnetic nanoparticles, especially magnetosomes, out of some of the body parts. ii) the percentage dissociation of at least one compound from the magnetic nanoparticles, in particular magnetosomes. iii) an increase in the number of temperature gradients or changes; and iv) an increase in the average temperature reached during treatment. In some embodiments, these decreases and increases occur during the course of continuous laser irradiation. and / or by comparison with the situation before or without the method or treatment. It is established by:

[0656] The present invention also relates to magnetic nanoparticles, in particular magnetosomes, for use, in which The application of the invention relates to the magnetic nanoparticles, particularly magnetosomes, The drug reduces the diffusion of the drug outside of some of the body parts that contain the drug. In one embodiment of the present invention, the part of the body that contains the magnetic nanoparticles, in particular magnetosomes, is magnetic. After administration of the nanoparticles, especially magnetosomes, -9 , 10 -6 , 10 -3 , 1, 10 3 , 106 , or 10 9 After a few seconds or more, it is part of the body part that has received the magnetic nanoparticles, particularly magnetosomes.

[0657] In one embodiment of the present invention, the part of the body that contains the magnetic nanoparticles, in particular magnetosomes, is magnetic. After administration of the nanoparticles, especially magnetosomes, -9 , 10 -6 , 10 -3 , 1, 10 3 , 10 6 , or 10 9 After a few seconds or less, some of the body parts have received the magnetic nanoparticles, particularly magnetosomes.

[0658] In another embodiment of the invention, the part of the body part is a pathological cell or a large amount of a pathological cell. Part, or 10 of pathological cells -20 , 10 -10 , 10 -5 , 10 -3 , 10 -1 , 1, 5, 10, 25, 50, 75, or 90% or more, where this percentage is the percentage of pathology contained in the body part. The number of target cells and the total number of cells or healthy and pathological cells in a body part It expresses the ratio between the sum of numbers.

[0659] In one embodiment of the invention, the body part is or comprises a part of the body part. In one embodiment of the present invention, the part of the body part is a body part comprising magnetic nanoparticles, in particular magnetosomes. It is a part of the body.

[0660] In another embodiment of the invention, the part of the body part comprises magnetic nanoparticles, in particular magnetosomes. It is a part of the body that cannot be moved.

[0661] In another embodiment of the invention, the portion of the body part is a portion of the body part containing pathological cells. be.

[0662] In another embodiment of the present invention, the portion of the body part is a portion of the body part that does not contain pathological cells. It is a department.

[0663] In another embodiment of the invention, the part of the body part is a part of the body part that does not contain healthy cells. It is.

[0664] In another embodiment of the invention, the portion of the body part is a portion of the body part that contains healthy cells. do.

[0665] In one embodiment of the present invention, the application of the sequence involves the preparation ...

Claims

1. In medical, biological, chemical or cosmetic treatments by sequential laser irradiation 2. A method of using magnetosomes to treat a body part of an individual, comprising administering said magnetosomes to said body part; and In a first step, the magnetosomes are irradiated with laser radiation at a first power; In the second step, the magnetosomes are exposed to a laser with a lower power than in the first step. Laser irradiation of magnetosomes or without laser irradiation of magnetosomes, and The sequence including the first step and the second step is repeated at least once. How to do it.

2. 2. Use of the magnetosomes of claim 1, wherein the magnetosomes are used to stimulate the action of magnetotaxis in living organisms, in particular magnetotaxis. How it is synthesized by sex cells.

3. A method of using magnetosomes according to any preceding claim, wherein said first s Step 2 further comprises heating or dissociating at least one compound from said magnetosomes or is a method that includes both.

4. The method of using magnetosomes according to claim 3, wherein the first step of heating is carried out according to the following formula: Group (1) an average heating temperature of less than 100 degrees Celsius; (2) an average heating temperature that is lower than the maximum temperature reached during processing; (3) A maximum heating temperature of 100 degrees Celsius or less; (4) some heating gradient greater than 2; and (5) Several heating temperatures reached by continuous irradiation of the magnetosomes with a laser. The magnetosomes are then laser-induced after at least two steps consisting of irradiation with a gradient of 100 nm or more. Several heating temperature gradients achieved by sequential irradiation with a laser, A method performed at a heating temperature characterized by at least one characteristic selected from

5. A method of using magnetosomes according to any preceding claim, wherein the second step The magnetosomes are cooled or the magnetosomes are not dissociated from at least one compound, or both. A method for constructing a

6. 6. The method of claim 5, wherein the second step of cooling comprises: Lower group (1) an average cooling temperature greater than 0 degrees Celsius; (2) some cooling temperature gradient greater than 2; A process carried out at a cooling temperature characterized by at least one property selected from

7. Use of magnetosomes according to claim 5 or claim 6, in which the second step The top is placed in the presence of an object or device intended to reduce the temperature of the body part or magnetosome. It is executed in i) the second step is performed from the time when such object or device does not exist to the time when such object or device does not exist; It becomes shorter when ii) The difference between the maximum and minimum temperatures in the second step is 、 iii) the power of the laser irradiating the magnetosomes during the first step is is lower when such object or device is present than when it is not present, iv) The concentration of magnetosomes in body parts is dependent on whether such objects or devices are It is lower when it is present than when it is absent, and v) At least the number of sequences performed during one session shall be such that more when the body or device is present than when it is not; How to make it so.

8. A method of using magnetosomes according to any preceding claim, wherein said first step The first step includes heating and the second step includes cooling, and the heating temperature of the first step and the The cooling temperature in the second step is stable or the first step or the second step. 10 in less than 99.9% of the time 5 , 10 3 , 10, 1 or 10 -1 A method that varies less than 1°C.

9. A method for using magnetosomes according to any of the preceding claims, comprising the steps of: or the second step or both, (1) 10 -50 and 10 50 minutes duration, and (2) The interstep period separating the first and second steps is 、 i) 10 -10 and 10 20 minutes, or ii) shorter than the duration of the first step or the second step Such a way.

10. A method of using magnetosomes according to any preceding claim, wherein said first s At least one of the sequences of the first step and the second step comprises: (1) 10 -50 Minutes and 10 50 The duration of the sequence in minutes, (2) 10 -10 Minutes and 10 20 the period between or between two sequences that is between minutes, (3) the duration of at least one sequence is greater than the duration of at least one step; and hand (4) The duration of at least one sequence or the duration of at least one step a period between at least one sequence; The method is characterized by at least one property selected from the group consisting of:

11. A method of using magnetosomes according to any preceding claim, comprising at least A sequence is a treatment session, where the treatment session consists of the following: group, (1) Each treatment session lasts 10 -50 Minutes and 10 5 Two treatment sessions lasting between 20 minutes and 25 minutes. There is a period between sessions, which is 10 -10 Minutes and 10 20 Between minutes, (2) at least one session is longer than the duration of at least one sequence; and (3) There is at least one session interval between two sessions, which is at least have a period greater than the period of at least one sequence, The method is characterized by at least one property selected from the group consisting of:

12. A method of using magnetosomes according to any preceding claim, wherein said first The first step or the second step or both may comprise at least one The dissociation of one compound is reached by a given percentage or the temperature GT of the first step is reached by a given percentage. FS or the predetermined temperature GT SS or both are reached. , where G.T. SS and G.T. FS The following groups: (1) GT SS GT FS Above (2) GT SS From GT FS minus 10 -5 and 10 5 °C, (3) GT SS or GT FS Or both are -273 and 10 3 °C, (4) GT SS is within the range of temperatures reached during hyperthermia, (5) GT FS is: i) -40 °C, ii) 0 °C, or iii) greater than 37 °C, (6) GT SS and GT FS is i) 100 °C, or ii) lower than the ablation temperature or 70 °C, and (7) GT SS and GT FS is 10 5 , 10 3 , 10, 5, 2 or 1 °C lower or 37 °C or physiological temperature Higher than The method is characterized by at least one property selected from the group consisting of:

13. A method of using magnetosomes according to any of the preceding claims, comprising at least Another sequence applies to the following groups: i) Diffusion of magnetosomes out of the body part containing magnetosomes Decrease in ii) an increase in the percentage of dissociation of at least one compound from magnetosomes; iii) An increase in the value of the temperature gradient or fluctuation; and iv) reduction in temperature reached during treatment; A method characterized by at least one of the following characteristics:

14. A method of using magnetosomes according to any preceding claim, comprising at least One sequence includes the following steps: i) the maximum temperature or maximum percentage of dissociation in the first step before treatment and and determining the minimum temperature or minimum percentage of dissociation in said second step; ii) the maximum temperature or maximum percentage dissociation in said first step, or both; setting or fixing the parameters of the laser to a first value to reach the subject, and Then, in order to reach a minimum temperature or a minimum percentage of dissociation or both in the second step, setting or fixing the parameter of the laser to a second value to iii) optionally, said first step or said second step or any of them The time periods for both to reach their maximum or minimum temperatures or maximum or minimum dissociation percentages are Measure as much as necessary to iv) optionally, said first step or said second step or Repeating the first step or the second step or both while measuring the period between them. thing, The method is carried out according to at least one of the following:

15. A method for sequentially irradiating magnetosomes with a laser, comprising: i) a first step of irradiating the magnetosomes with laser radiation at a first power; Step ii) Optionally, the irradiated magnetospheric material obtained in the first step The magnetosomes obtained in the first step are not irradiated, or the irradiated magnetosomes obtained in the first step are irradiating the substrate with laser radiation having a second power output lower than the first power output; iii) repeating said step or steps for at least one sequence. A method comprising:

16. 16. A magnetosome irradiated according to claim 15, comprising the following group: (1) The size of the irradiated magnetosomes is larger than that of non-irradiated magnetosomes. R10 -3 % and 99.99%, where this percentage is S I S NI Relative to Or S NI From S I S minus NI is the ratio to S NI and S. I are non-irradiated and irradiated, respectively. The size of the projectile magnetosome is (2) The number of irradiated compounds wrapped around the irradiated magnetosome, n I is a non-irradiated magneto The number of compounds wrapped around the I smaller, where n NI / n I is 1 and 10 10 Between . (3) At least one bond between the irradiated compound and the irradiated magnetosome. Destroy (4) The bond dissociation energy E between the irradiated compound and the irradiated magnetosome dI teeth , the bond dissociation energy E between the non-irradiated compound and the non-irradiated magnetosome dNI , less than, (5) Coating thickness CT of irradiated magnetosomes I of non-irradiated magnetosomes Coating thickness CT NI ,Thinner, (6) The percentage of organic material or carbon by mass in irradiated magnetosomes is 0.1% compared to that of non-irradiated magnetosomes. The percentage of organic material or carbon in the netosome mass is less than the percentage of the irradiated magnetosome. The scattering of irradiated compounds wrapped around magnetosomes is the scattering of non-irradiated compounds wrapped around non-irradiated magnetosomes. smaller than the clutter of mixtures, and (7) Irradiated compound N from irradiated magnetosomes 2I Prevents the release of irradiated Number of compounds N 1I is the amount of non-irradiated compound N from non-irradiated magnetosomes. 2NI Non-irradiation prevents the release of Number of compounds N 1NI Less In the above, the non-irradiated magnetosomes are those that are not exposed to laser irradiation or are exposed to continuous laser irradiation. Magnetosomes exposed to irradiation, Irradiated magnetosomes having at least one characteristic selected from the following:

17. 17. The irradiated magnetosome according to claim 16, wherein the magnetosome is a biospecific Magnetosomes synthesized by magnetotactic bacteria.

18. A compound, in particular a cosmetic, medical or diagnostic compound, comprising an irradiated compound according to claim 16 or 17. The magnetosomes and the following groups: (1) the color of the body part; (2) Contrast of said body parts (3) the imaging capability of the body part; and (4) The ability to treat or repair said body part. At least one of the following methods for modifying at least one characteristic of the body part: Coloring or contrasting agents, diagnostic agents, or therapeutic agents It consists of quality.

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