Compositions and methods for photohyperthermia

Abstract

Described herein, in aspects, is a photohyperthermia composition comprising magnetic plasmonic nanoparticles. Also described is a method of locally heating a tissue of interest in a subject, the method comprising administering the composition to the subject and applying near-infrared light to the tissue of interest. Also described is a method of sterilizing an animal with testicles, the method comprising heating the testicles with nanoparticle-mediated photohyperthermia. Related devices for use in the methods described herein are also described.

Description

[0001] COMPOSITIONS AND METHODS FOR PHOTOHYPERTHERMIA

[0002] Field

[0003] Described herein are nanoparticles. More specifically, described herein are plasmonic nanoparticle compositions and methods for photohyperthermia.

[0004] Background

[0005] Photohyperthermia, or photothermal therapy, is the process of a photothermal agent absorbing light and converting it into heat for the destruction of germinative cells , which is due to elevated temperatures. This technique is non-invasive, can target testicle cells for minimal adverse side effects, and can be used in conjunction with other methods.

[0006] Description of the Drawings

[0007] The present invention will be further understood from the following description with reference to the Figures, in which:

[0008] Figure 1. A depiction of surface plasmon resonance (SPR).

[0009] Figure 2. A saline solution under LED light at 808 nm is shown in green. A saline solution with the nanoparticles described herein under LED light at 808 nm is shown in black. The LED increase in potency is shown in blue.

[0010] Figure 3. An image of the nanoparticles under an LED light at 808 nm.

[0011] Figure 4. The temperature profile of a nanoparticle solution placed under an LED light at 808 nm at full potency.

[0012] Figure 5. The temperature profile of a saline solution placed under an LED light at 808 nm at full potency.

[0013] Figure 6. The temperature profile of rat testicles injected with the nanoparticles and placed under an LED light at 808 nm.

[0014] Summary

[0015] In accordance with an aspect, there is provided a photohyperthermia composition comprising magnetic plasmonic nanoparticles.

[0016] In an aspect, the nanoparticles are stable and biocompatible.

[0017] In an aspect, the nanoparticles comprise iron.

[0018] In an aspect, the nanoparticles comprise iron oxide.

[0019] In an aspect, the nanoparticles are surface-passivated.

[0020] In an aspect, the nanoparticles are doped.

[0021] In an aspect, the nanoparticles are doped with manganese.

[0022] In an aspect, the nanoparticles are functionalized to improve stability and / or biocompatibility. In an aspect, the nanoparticles are functionalized with citrate to improve stability at physiological pH.

[0023] In an aspect, the optical response of the nanoparticles is tunable for different applications.

[0024] In an aspect, the nanoparticles are resonate in response to light in the near-infrared range, such as from about 750 nm to about 1400 nm.

[0025] In an aspect, the nanoparticles resonate in response to light at about 808 nm.

[0026] In an aspect, the light is LED light.

[0027] In accordance with an aspect, there is provided a method of locally heating a tissue of interest in a subject, the method comprising administering the composition described herein to the subject and applying near-infrared light to the tissue of interest.

[0028] In an aspect, the method further comprises magnetically guiding the nanoparticles to the tissue of interest prior to applying the light.

[0029] In an aspect, the composition is administered to the tissue of interest.

[0030] In an aspect, the method is for ablating a tissue.

[0031] In an aspect, the tissue is gonadal tissue.

[0032] In an aspect, the gonadal tissue comprises testes.

[0033] In accordance with an aspect, there is provided a method of sterilizing an animal with testicles, the method comprising heating the testicles with nanoparticle-mediated photohyperthermia.

[0034] In an aspect, the method comprises administering the composition described herein to the animal.

[0035] In an aspect, the animal is a non-human mammal.

[0036] In an aspect, the animal is a cat or a dog.

[0037] In an aspect, the animal is livestock.

[0038] In an aspect, the composition is administered to the testicles.

[0039] In an aspect, the composition is administered to the cranial and caudal regions of the testicle to improve homogeneity of the composition in the testicle.

[0040] In an aspect, the photohyperthermia comprises administering light in the near-infrared range, such as from about 750 nm to about 1400 nm, to the testicles.

[0041] In an aspect, the light is about 808 nm.

[0042] In an aspect, the light is LED light.

[0043] In an aspect, the method comprises placing the testicle between two light sources.

[0044] In an aspect, the method further comprises use of a thermocouple to monitor testicle temperature and control the intensity of the light.

[0045] In an aspect, the method comprises heating the testicles to a temperature of about 45°C for about 15 minutes. In accordance with an aspect, there is provided a device for nanoparticle-mediated photohyperthermia sterilization of animals with testicles, the device comprising at least two light sources between which the testicle can be placed, at least one thermocouple to detect the testicle temperature and control the intensity of the light.

[0046] Other features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples while indicating embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from the detailed description.

[0047] Detailed Description

[0048] Plasmonic nanoparticles, including gold, silver and platinum particles, are discrete metallic particles that have unique optical properties due to their size and shape, and are increasingly being incorporated into commercial products and technologies. These technologies, which span fields ranging from photovoltaics to biological and chemical sensors, take advantage of the extraordinary efficiency of plasmonic nanoparticles at absorbing and scattering light. Additionally, unlike most dyes and pigments, plasmonic nanoparticles have a color that depends on their size and shape and can be tuned to optimize performance for individual applications without changing the chemical composition of the material: for example, the solutions described herein contain gold or silver nanoparticles with controlled size and shape that tunes their optical response, resulting in vibrantly colored dispersions.

[0049] The remarkable optical properties of plasmonic materials occur because the conduction electrons on the nanoparticle surface undergo a collective oscillation when excited by light at specific wavelengths (Figure 1). This oscillation, which is known as a surface plasmon resonance (SPR), results in the unusually strong scattering and absorption of light. When these resonances are excited, absorption and scattering intensities can be up to 40x higher than identically sized particles that are not plasmonic.

[0050] Metallic nanoparticles can generate heat in many ways. In the case of photohyperthermia, when light hits metallic nanoparticles, energy is absorbed by electrons on the surface of the particles, which are excited to higher energy states. The tendency is for the electron to return to its original valence, and for that it needs to lose the energy it gained from light (to move to higher energy states). This energy is then dissipated as heat, causing a localized temperature rise in the area around the particles. The process of converting light energy into heat is known as the plasmonic effect, which occurs due to collective oscillations of electrons on the surface of metallic particles. The plasmonic effect is particularly strong in nanometer-sized metallic nanoparticles, which allows efficient light absorption and generation of a localized temperature increase. Definitions

[0051] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. See for example Singleton et aL, Dictionary of Microbiology and Molecular Biology 2nded., J. Wiley & Sons (New York, N.Y. 1994); Sambrook et aL, Molecular Cloning. A Laboratory Manual, Cold Springs Harbor Press (Cold Springs Harbor, NY 1989), each of which is incorporated herein by reference. For the purposes of the present invention, the following terms are defined below.

[0052] The terms "therapeutically effective amount", "effective amount" or "sufficient amount" mean a quantity sufficient, when administered to a subject, including a mammal, for example, a pet or livestock, to achieve the desired result, for example, an amount effective to sterilize an animal. Effective amounts of the molecules described herein may vary according to factors such as the age, sex, and weight of the subject. Dosage or treatment regimens may be adjusted to provide the optimum therapeutic response, as is understood by a skilled person.

[0053] Likewise, an “effective amount” of the compounds described herein refers to an amount sufficient to function as desired, such as to cause sterility.

[0054] Administration "in combination with" one or more further therapeutic agents includes simultaneous (concurrent) and consecutive administration in any order.

[0055] The term “pharmaceutically acceptable” means that the compound or combination of compounds is compatible with the remaining ingredients of a formulation for pharmaceutical use and that it is generally safe for administering to animals according to established governmental standards, including those promulgated by the United States Food and Drug Administration.

[0056] "Carriers" as used herein include pharmaceutically acceptable carriers, excipients, or stabilizers that are nontoxic to the cell or subject being exposed thereto at the dosages and concentrations employed. Often the pharmaceutically acceptable carrier is an aqueous pH buffered solution. Examples of pharmacologically acceptable carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, and dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol and sorbitol; salt-forming counterions such as sodium; and / or non-ionic surfactants such as TWEEN™, polyethylene glycol (PEG), and PLURONICS™.

[0057] In understanding the scope of the present application, the articles “a”, “an”, “the”, and “said” are intended to mean that there are one or more of the elements. Additionally, the term "comprising" and its derivatives, as used herein, is intended to be open-ended terms that specify the presence of the stated features, elements, components, groups, integers, and / or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and / or steps. The foregoing also applies to words having similar meanings such as the terms, "including", "having", and their derivatives.

[0058] It will be understood that any embodiments described as “comprising” certain components may also “consist of or “consist essentially of,” wherein “consisting of has a closed-ended or restrictive meaning and “consisting essentially of means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect of the invention. For example, a composition defined using the phrase “consisting essentially of encompasses any known pharmaceutically acceptable additive, excipient, diluent, carrier, and the like. Typically, a composition consisting essentially of a set of components will comprise less than 5% by weight, typically less than 3% by weight, more typically less than 1% by weight of non-specified components.

[0059] It will be understood that any component defined herein as being included may be explicitly excluded from the claimed invention by way of proviso or negative limitation. For example, in embodiments, magnetic metals such as iron are explicitly excluded from the compositions and methods described herein. In other embodiments, non-magnetic metals, such as gold, platinum, or silver are explicitly excluded from the compositions and methods described herein.

[0060] In addition, all ranges given herein include the end of the ranges and also any intermediate-range points, whether explicitly stated or not.

[0061] Finally, terms of degree such as "substantially", "about" and "approximately" as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ± 5% of the modified term if this deviation would not negate the meaning of the word it modifies.

[0062] Methods and Compositions

[0063] The present invention is in the fields of veterinary medicine and public health and relates to a process that promotes sterility in male animals without the need for a surgical approach. The process is based on the increase in testicular temperature, through photohyperthermia mediated by nanoparticles. Initially, a fluid composed of manganese ferrite nanoparticles functionalized with citrate is injected into the testes, which are subsequently subjected to LED light in the near-infrared range (808 nm), promoting heating of the testes and sterilization of the animals. The complete procedure takes about 30 minutes and is performed only once.

[0064] The fact that it does not involve surgery facilitates the handling of the animal, as it does not require preoperative examinations or postoperative treatment and follow-up, does not require a sterile environment, and reduces the risk of infection. Thus in aspects, described herein is

[0065] Thus described herein is a photohyperthermia composition comprising plasmonic nanoparticles. Typically, the nanoparticles are stable and biocompatible.

[0066] While the nanoparticles may comprise any metal, including magnetic or non-magnetic metals, typically they comprise magnetic metals such as iron and, more specifically, they typically comprise iron oxide.

[0067] Typically, the nanoparticles are surface-passivated in order to enrich them with metal, such as iron. Further, the nanoparticles are typically doped, such as with manganese.

[0068] In aspects, the nanoparticles are functionalized to improve stability and / or biocompatibility, such as with citrate to improve stability at physiological pH.

[0069] It will be understood that, in aspects, the optical response of the nanoparticles is tunable for different applications. Typically, the nanoparticles are resonate in response to light in the near-infrared range, such as from about 750 nm to about 1400 nm, such as about 750, about 800, about 900, about 1000, about 1100, about 1200, or about 1300, to about 800, about 900, about 1000, about 1100, about 1200, about 1300, or about 1400 nm, such as from about 800 to about 850 nm, such as about 808 nm. Typically, the light is LED light.

[0070] Also described herein is a method of locally heating a tissue of interest in a subject, the method comprising administering the composition described herein to the subject and applying near-infrared light to the tissue of interest. Related uses of the composition are also contemplated.

[0071] In aspects, the method further comprises optionally magnetically guiding the nanoparticles to the tissue of interest prior to applying the light.

[0072] In aspects, the composition is administered to the tissue of interest.

[0073] It will be understood that the methods described herein can be used for ablating a tissue. Typically, the tissue is gonadal tissue and typically the gonadal tissue comprises testes.

[0074] Thus, also described herein is a method of sterilizing an animal with testicles, the method comprising heating the testicles with nanoparticle-mediated photohyperthermia.

[0075] Typically, the method comprises administering the composition described herein to the animal, which is typically a non-human mammal. While the methods described herein could be used in any animal with testes, including humans, it is typically used in cats, dogs, other pets, or livestock, for example.

[0076] Thus, in typical aspects, the composition is administered to the testicles and, more specifically, it is typically administered to the cranial and caudal regions of the testicle to improve homogeneity of the composition in the testicle.

[0077] Typically, the photohyperthermia comprises administering light in the near-infrared range, such as from about 750 nm to about 1400 nm, to the testicles, as described above. Typically, the light is about 808 nm and typically is LED light.

[0078] In typical aspects, the methods comprises placing the testicle between two light sources. Typically, the method comprises use of a thermocouple to monitor testicle temperature and control the intensity of the light.

[0079] In typical aspects, the method comprising heating the testicles to a temperature of about 45°C for about 15 minutes, such as about 40°C, 41 °C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C, or 50°C for about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 minutes, or any combination thereof that is sufficient to sterilize the animal.

[0080] Also described herein is a device for nanoparticle-mediated photohyperthermia sterilization of animals with testicles, the device comprising at least two light sources between which the testicle can be placed, at least one thermocouple to detect the testicle temperature and control the intensity of the light.

[0081] The production of magnetic fluid typically occurs from the synthesis of nanoparticles based on iron oxide, which typically undergo a passivation process (iron enrichment). Passivation typically contains more than one dopant, with manganese being the main dopant of nanoparticles. Next, the nanoparticles typically undergo molecular coating with citric acid, which refers to their functionalization, increasing stability at physiological pH. The molecular coating process combined with surface passivation of iron oxide-based nanoparticles improves stability and biocompatibility.

[0082] The electromagnetic wave generation system is based on a light source (typically 2 LEDs positioned parallel and facing each other) which emit light in the near infrared range (typically at a wavelength of about 808 nm) with variable and adjustable power of according to the temperature reached in the target organ.

[0083] The application of the magnetic fluid is typically performed with a total volume of 150 pL in each testicle, divided into two regions (cranial and caudal) of each testicle, with the aim of distributing the nanoparticles more homogeneously in the organ. For the injection, the animal is anesthetized, placed in dorsal decubitus and the scrotum is antisepsis.

[0084] After the injection, the animal is typically accommodated with the region of the testicles positioned between the two LEDs, equidistantly (approximately 5 cm away from both LEDs), and a thermocouple is attached to each testicle for monitoring and feeding the injection system and for temperature control. Then the equipment is turned on and the testicles are exposed to light. When subjected to electromagnetic light waves, the nanoparticles inside the testicular tissue promote the elevation of the local temperature from the inside out, in a homogeneous and controlled way.

[0085] Typically, from this moment on, the increase in temperature is monitored until the surface of the testicle reaches a temperature of approximately 45°C, which occurs within about 5 to about 10 minutes. Then, this temperature is kept constant for a period of about 15 minutes. This procedure is done by automatically adjusting the power of the LED. When this time is reached, the equipment is turned off. Sterilization is due to increased testicular temperature.

[0086] In typical aspects, the following steps are followed. Photohyperthermia castration process: i. Anesthesia of the animal, and positioning it in dorsal decubitus; ii. Antisepsis of the testicles and injection of 150 pL of the magnetic fluid into each testicle of the animal (this volume is divided into two regions of the testicle); iii. Accommodation of the animal by positioning the testicles between the LEDs and coupling two thermocouples (one to each testicle) to monitor the testicular temperature and power the temperature control system; iv. Activating the LEDs to emit light at a wavelength of 808 nm; v. Monitoring the increase in temperature until the surface of the testicle reaches 45°C;

[0087] The device that mediates photothermal therapy for sterilization consists of two light sources aimed at each other, two temperature probes, some control circuitry and a user interface. The animal’s testicles should be placed at the midpoint between the light sources with each temperature probe touching each testicle. This device works in a dynamic feedback loop: every second it measures the testicle’s temperature and uses it to calculate how much power to deliver to the light sources, thus controlling testicle temperature. This control over power delivery is built upon Pulse-width modulation (PWM) technology. Each light source is an array of LEDs (808 nm) with a maximum power output of about 60 Watts and must be actively cooled. The cooling is accomplished by a typical PC processor water cooler.

[0088] The control circuitry is based on a microprocessing unit (MPU). It uses a discrete-time PI (Proportional Integral) control law to calculate PWM duty cycle. Due to their relatively high power consumption, the light sources are switched on and off indirectly by the MPU through an LED driver. This driver is built with a MOSFET constant-current source that was designed specifically for the device’s light sources. The PI controller parameters were tuned in a simulation environment and then tested with real animals and adjusted. The simulation environment was modeled using an ARX model and trained on data from tests with animals.

[0089] The user interface consists of a thin-film transistor capacitive touch liquid crystal display and some C++ software run by the MPU. The authorial software is best described as a framework for displaying elements on screen and is built upon some open source (BSD license) libraries.

[0090] The compositions may be formulated for use by a subject, such as a mammal. Compositions comprising the nanoparticles described herein may comprise about 0.00001% to about 99% by weight of the nanoparticles and any range there-in-between, such as from about 0.00001%, about 0.0001%, about 0.001%, about 0.01%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.5%, about 99.7%, or about 99.9%, to about 0.0001 %, about 0.001 %, about 0.01 %, about 0.1 %, about 0.5%, about 1 %, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.5%, about 99.7%, about 99.9%, about 99.99%. For example, typical doses may comprise from about 0.1 pg to about 1000 mg of the nanoparticles described herein per ml, such as about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 20 mg, about 25 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 75 pg, about 100 mg, about 125 mg, about 150 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 750 mg, or about 1000 mg per ml, such as from about 30 mg to about 100 mg per ml (and all related increments and percentages by weight).

[0091] The compositions described herein may be used in any suitable amount, but are typically provided in doses comprising from about 1 to about 10000 ng / kg, such as from about 1 to about 1000, about 1 to about 500, about 10 to about 250, or about 50 to about 100 ng / kg, such as about 1, about 10, about 25, about 50, about 75, about 100, about 150, about 200, about 250, about 300, or about 500 ng / kg. In other aspects, the compositions described herein are provided in doses of from about 1 to about 10000 mg per dose, such as from about 1 to about 1000, about 1 to about 500, about 10 to about 250, or about 50 to about 100 mg, such as about 1 , about 10, about 25, about 50, about 75, about 100, about 150, about 200, about 250, about 300, about 400, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, or about 1000 mg.

[0092] Typically, the compositions are administered once and the sterilization is completed after the single administration. The compositions may however be administered over a period of hours, days, weeks, or months, depending on several factors, including size and weight of the animal , etc. The administration may be constant, e.g., constant infusion over a period of hours, days, weeks, months, etc. Alternatively, the administration may be intermittent, e.g., the composition may be administered once a day over a period of days, once an hour over a period of hours, or any other such schedule as deemed suitable.

[0093] The compositions described herein can be prepared by perse known methods for the preparation of pharmaceutically acceptable compositions which can be administered to subjects, such that an effective quantity of the active substance is combined in a mixture with a pharmaceutically acceptable vehicle. Suitable vehicles are described, for example, in "Handbook of Pharmaceutical Additives" (compiled by Michael and Irene Ash, Gower Publishing Limited, Aidershot, England (1995)). On this basis, the compositions include, albeit not exclusively, solutions of the substances in association with one or more pharmaceutically acceptable vehicles or diluents, and may be contained in buffered solutions with a suitable pH and / or be iso-osmotic with physiological fluids. In this regard, reference can be made to U.S. Patent No. 5,843,456 (the entirety of which is incorporated herein by reference).

[0094] Pharmaceutically acceptable carriers are well known to those skilled in the art and include, for example, sterile saline, lactose, sucrose, calcium phosphate, gelatin, dextrin, agar, pectin, peanut oil, olive oil, sesame oil, cannabis oil, and water. Furthermore, the composition may comprise one or more stabilizers such as, for example, carbohydrates including sorbitol, mannitol, starch, sucrose, dextrin, and glucose, proteins such as albumin or casein, and buffers like alkaline phosphates.

[0095] The compositions described herein can, in embodiments, be administered for example, by parenteral, intravenous, subcutaneous, intradermal, intramuscular, intracranial, intrathecal, intraorbital, ophthalmic, intraventricular, intracapsular, intraspinal, intracisternal, intraperitoneal, intranasal, intrarectal, intravaginal, aerosol, oral, topical, or transdermal administration. Typically, the compositions of the invention are administered intravenously or directly into the tissue of interest, such as intragonadally.

[0096] It is understood by one of skill in the art that the compositions described herein can be used in conjunction with known therapies for sterilization. The compositions described herein may be formulated together with such conventional treatments when appropriate.

[0097] The above disclosure generally describes the present invention. A more complete understanding can be obtained by reference to the following specific Examples. These Examples are described solely for purposes of illustration and are not intended to limit the scope of the invention. Changes in form and substitution of equivalents are contemplated as circumstances may suggest or render expedient. Although specific terms have been employed herein, such terms are intended in a descriptive sense and not for purposes of limitation.

[0098] Examples

[0099] Example 1

[0100] Figure 2 shows a saline solution under LED light at 808 nm in green. The nanoparticles used here were the iron oxide nanoparticles doped with manganese and functionalized with citrate. A saline solution with the nanoparticles described herein under LED light at 808 nm is shown in black. The LED increase in potency is shown in blue. Figure 3 shows an image of the nanoparticles under an LED light at 808 nm.

[0101] Example 2

[0102] A nanoparticle solution and a saline solution were placed under an LED light at 808 nm at full potency. The maximum temperature reach by the nanoparticle solution was 63 °C in 400 seconds (Figure 4) , whereas the maximum temperature for the saline solution under the same LED was 41 °C (Figure 5). This represents a more than 20 °C increase due to the photothermal effect.

[0103] Example 3

[0104] Photohyperthermia castration process was demonstrated. The animal (rat) was anesthetized and 150 pL of the magnetic fluid was injected into each testicle and positioned in dorsal decubitus; two thermocouples (one to each testicle) were installed to monitor the testicular temperature. The animal’s testicles were positioned between the LEDs, which were activated to emit light at a wavelength of 808 nm. The increase in temperature was monitored on the testicles. Different LED potencies were used to monitor the increase in temperature (Figure 6).

Claims

Claims1. A photohyperthermia composition comprising magnetic plasmonic nanoparticles.

2. The composition of claim 1 , wherein the nanoparticles are stable and biocompatible.

3. The composition of claim 1 or 2, wherein the nanoparticles comprise iron.

4. The composition of claim 3, wherein the nanoparticles comprise iron oxide.

5. The composition of any one of claims 1 to 4, wherein the nanoparticles are surface- passivated.

6. The composition of any one of claims 1 to 5, wherein the nanoparticles are doped.

7. The composition of claim 6, wherein the nanoparticles are doped with manganese.

8. The composition of any one of claims 1 to 7, wherein the nanoparticles are functionalized to improve stability and / or biocompatibility.

9. The composition of claim 8, wherein the nanoparticles are functionalized with citrate to improve stability at physiological pH.

10. The composition of any one of claims 1 to 9, wherein the optical response of the nanoparticles is tunable for different applications.

11. The composition of any one of claims 1 to 10, wherein the nanoparticles are resonate in response to light in the near-infrared range, such as from about 750 nm to about 1400 nm.

12. The composition of claim 11 , wherein the nanoparticles resonate in response to light at about 808 nm.

13. The composition of claim 11 or 12, wherein the light is LED light.

14. A method of locally heating a tissue of interest in a subject, the method comprising administering the composition of any one of claims 1 to 13 to the subject and applying near-infrared light to the tissue of interest.

15. The method of claim 14, further comprising magnetically guiding the nanoparticles to the tissue of interest prior to applying the light.

16. The method of claim 15, wherein the composition is administered to the tissue of interest.

17. The method of any one of claims 14 to 16, for ablating a tissue.

18. The method of claim 17, wherein the tissue is gonadal tissue.

19. The method of claim 18, wherein the gonadal tissue comprises testes.

20. A method of sterilizing an animal with testicles, the method comprising heating the testicles with nanoparticle-mediated photohyperthermia.

21. The method of claim 20, wherein the method comprises administering the composition of any one of claims 1 to 13 to the animal.

22. The method of claim 21 or 22, wherein the animal is a non-human mammal.

23. The method of claim 22, wherein the animal is a cat or a dog.

24. The method of claim 22, wherein the animal is livestock.

25. The method of any one of claims 20 to 24, wherein the composition is administered to the testicles.

26. The method of claim 25, wherein the composition is administered to the cranial and caudal regions of the testicle to improve homogeneity of the composition in the testicle.

27. The method of any one of claims 20 to 26, wherein the photohyperthermia comprises administering light in the near-infrared range, such as from about 750 nm to about 1400 nm, to the testicles.

28. The method of claim 27, wherein the light is about 808 nm.

29. The method of claim 27 or 28, wherein the light is LED light.

30. The method of any one of claims 20 to 29, comprising placing the testicle between two light sources.

31. The method of any one of claims 20 to 30, further comprising use of a thermocouple to monitor testicle temperature and control the intensity of the light.

32. The method of any one of claims 20 to 31 , the method comprising heating the testicles to a temperature of about 45°C for about 15 minutes.

33. A device for nanoparticle-mediated photohyperthermia sterilization of animals with testicles, the device comprising at least two light sources between which the testicle can be placed, at least one thermocouple to detect the testicle temperature and control the intensity of the light.

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