Gold particles and uses thereof

Abstract

Systems and methods for minimally-invasive lipolysis in a target area by injecting the area with a solution of photo-absorbing nanoparticles such as substantially spherical gold nanoshells that may comprise a non-conducting core, and irradiating the injected area with a beam of near infrared (NIR) light adapted to excite the nanoparticles to melt or ablate fat within the target area.

Description

ELUX-001-PCTGOLD PARTICLES AND USES THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to United States Provisional Application No.63 / 698,277, filed September 24, 2024, the entire contents of which are incorporated herein by reference.FIELD

[0002] The present disclosure relates, at least in part, to uses of nanoparticles and in certain embodiments gold nanoshells.BACKGROUND

[0003] United States Patent No.6,530,944 discloses “[a] method for inducing localized hyperthermia in a cell or tissue comprising the steps of delivering nanoparticles to said cell or tissue and exposing said nanoparticles to infrared radiation under conditions wherein said nanoparticles emit heat upon exposure to said infrared radiation.”

[0004] PCT Patent Application No. WO2012 / 027728 (https: / / patents.google.com / patent / WO2012027728A2 / en) discloses “nanoparticles and formulations which are useful for cosmetic, diagnostic and therapeutic applications to mammals such as humans.” The nanoparticles of the ‘728 application can be “nanoplates, solid nanoshells, hollow nanoshells, nanorods, nanorice, nanospheres, nanofibers, nanowires, nanopyramids, nanoprisms, nanostars or a combination thereof” and that “[d]iseases or conditions suitable for treatment with subdermatological applications include wrinkles and tattoos. Other applications include skin rejuvenation and / or resurfacing, the removal or reduction of stretch marks and fat ablation.”

[0005] PCT Patent Application No. WO2013 / 169955 (https: / / patents.google.com / patent / WO2013169955A1) discloses an “apparatus and method … [that] combines near infrared (NIR) light exposure and a solution of gold nanorods (GNRs) that may be injected into the treatment target in order to selectively heat fat in the target area.”1ELUX-001-PCT

[0006] PCT Patent Application No. WO2015054493 (https: / / patents.google.com / patent / WO2015054493A1) discloses “a material composition comprises a plurality of particles, wherein each particle comprises a core and a shell encapsulating the core, the shell comprising at least one atomic element not included in the core.”

[0007] PCT Patent Application No. WO / 2018 / 112261 (https: / / patents.google.com / patent / WO2018112261A1 / ) discloses “methods, systems, and devices for treating tissue ablation are disclosed” and that in “some embodiments, the system provides sub-ablative infrared radiation that is absorbed by nanoparticles.” SUMMARY

[0008] The present disclosure in various aspects and embodiments provides, inter alia, systems and methods for minimally-invasive lipolysis in a target area by injecting the area with a solution of photo-absorbing nanoparticles and irradiating the injected area with a beam of near infrared (NIR) light. The NIR emission wavelength may in certain embodiments be adapted to excite the nanoparticles to melt fat within the target area; in some embodiments so that the liquefied fat can be aspirated from the target area, or in some embodiments such that aspiration of the liquified fat is not needed. In certain aspects and embodiments the nanoparticles are be gold nanoshells; for example, substantially spherical gold nanoshells that may comprise a non-conducting core.

[0009] As used herein the term “nanoparticle” means a particle having at least one axial dimension (diameter / length) that is between 1 and 1,000nm. Nanoparticles suitable for use in conjunction with the present disclosure include any nanoparticle that is adapted to at least partially transduce an external energy into heat energy for elevating the temperature of a target area. Suitable examples of such nanoparticles and their methods of production and functionalization are known in the art. See e.g., U.S. Patent Nos.6,344,272 and 6,685,986; and PCT Patent Application Nos. WO2012 / 027728, WO2013 / 169955, WO2015054493, and WO / 2018 / 112261—each of which are hereby incorporated by reference in their entirety herein. These transducing nanoparticles include, among others: nanoshells (including gold-shell silica core nanoshells, gold-gold sulfide nanoshells and other variants), metal nanorods, nanostars, hollow nanoparticles, nanocages, elliptical "nanorice," carbon particles, fullerenes, carbon fullerenes, metallic2ELUX-001-PCTnanoparticles, metal colloids, carbon particles, carbon nanotubes, buckyballs, and any combination thereof. In many, or most, of the embodiments of the present disclosure, the nanoparticles are photo-absorbing nanoparticles. In some embodiments the nano particles are substantially spherical. In some embodiments the nano particles are spherical. In some embodiments, the nanoparticles have an aspect ratio in the range of 1:1 to 1:2. In some embodiments the nanoparticles comprise a core and a shell encapsulating the core, wherein said shell comprises at least one atomic element not included in the core. In some embodiments the nanoparticles have at least one axial dimension (diameter / length) longer than 100 nm.

[0010] As used herein, the term “nanoshell” means a nanoparticle that includes at least one non-conducting core layer and at least one conducting shell layer. In some embodiments the nanoshells are substantially spherical. In some embodiments the nanoshells are spherical. In some embodiments, the nanoshells have an aspect ratio in the range of 1:1 to 1:2. In some embodiments the nanoparticles have at least one axial dimension (diameter / length) longer than 100 nm. In some embodiments, a nanoshell of the disclosure has an aspect ratio of about 1:1.

[0011] In some embodiments, the non-conducting core of a nanoshell of the disclosure includes dielectric materials and / or semiconductors. In certain embodiments; the core includes one or more selected from the group consisting of silicon dioxide (silica), titanium dioxide, polymethyl methacrylate (PMMA), polystyrene, gold sulfide and macromolecules such as dendrimers. In some embodiments, the core includes one or more selected from the group consisting of CdSe, CdS or GaAs.

[0012] In some embodiments, the conducting shell layer of a nanoshell of the disclosure includes one or more metals selected from the group consisting of gold, silver, copper, platinum, palladium, lead, iron and the like. In some embodiments, the conducting shell layer includes gold. In some embodiments, the conducting shell layer includes silver.

[0013] Accordingly, in one aspect, a method for fat removal and / or skin tightening in a subject is provided wherein the method includes injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said3ELUX-001-PCTsubject and delivering a series of pulses of near infrared light across an area of skin overlying the target area.

[0014] In another aspect, a method for fat removal and / or skin tightening in a subject is provided wherein the method includes injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise at least one non-conducting core layer and at least one conducting shell layer.

[0015] In a further aspect, a method for fat removal and / or skin tightening in a subject is provided wherein the method includes injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have at least one axial dimension (diameter / length) longer that 100 nm.

[0016] In yet another aspect, a method for fat removal and / or skin tightening in a subject is provided wherein the method includes injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have an aspect ratio in the range of 1:1 to 1:2.

[0017] In an additional aspect, a method for fat removal and / or skin tightening in a subject is provided wherein the method includes injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles are substantially spherical.

[0018] In a further additional aspect, a method for fat removal and / or skin tightening in a subject is provided wherein the method includes injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise a core and a shell4ELUX-001-PCTencapsulating the core, wherein said shell comprises at least one atomic element not included in the core.

[0019] In some embodiments, a nanoshell of the disclosure has a diameter between 80-500 nm; or between 100-200 nm; or between 125-175 nm; or between 150-170 nm; or about 125 nm; or about 150 nm; or about 160 nm; or about 170 nm; or about 175 nm; or about 200 nm.

[0020] In some embodiments, a nanoshell of the disclosure has a diameter between 80-500 nm; or between 100-200 nm; or between 125-175 nm; or between 150-170 nm; or about 125 nm; or about 150 nm; or about 160 nm; or about 170 nm; or about 175 nm; or about 200 nm.

[0021] In some embodiments, a nanoshell of the disclosure has a conducting shell layer that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.

[0022] In some embodiments, a nanoshell of the disclosure has a conducting shell layer comprising gold that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.

[0023] In some embodiments, a nanoshell of the disclosure has a conducting shell layer comprising silver that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.

[0024] In some embodiments, nanoparticles of the disclosure comprise a core and a shell encapsulating the core, the shell comprising at least one atomic element not included in the core, wherein the cores have: a median maximum dimension that is less than 10 microns, and a median of at least one axial dimension that is in the range of 10 nm to 500 nm, and wherein the shells have: a median thickness that is less than 100 nm, a silicon concentration that is in the range of 10% to 50% on the basis of the weight of the shells, and an aluminum concentration that is in the range of 0.01% to 5% on the basis of the weight of the shells. In certain embodiments, nanoparticles of the disclosure comprise a core a core and a shell encapsulating the core, the shell comprising at least one atomic5ELUX-001-PCTelement not included in the core, wherein the cores have: a median maximum dimension that is less than 10 microns, and a median of at least one axial dimension that is in the range of 10 nm to 500 nm, and wherein the shells have: a median thickness that is less than 100 nm, a silicon concentration that is in the range of 10% to 50% on the basis of the weight of the shells, and an aluminum concentration that is in the range of 0.01% to 5% on the basis of the weight of the shells, wherein the shells have a ratio of the aluminum concentration to the silicon concentration in the range of 1:20 to 1:5000 such that the median thickness does not change by more than 10% when measured 24 hours after immersing in water. In certain embodiments, the nanoparticles are nanoshells (for example gold or silver nanoshells) in accordance with the claims and / or disclosures of US Patent No.9,9675,953.

[0025] In some embodiments of any of the methods described herein, the solution of photo-absorbing nanoparticles administered to the subject has nanoparticles (such as, for example, spherical nanoshells) in a concentration between 0.5 and 50 OD; or between 0.25 and 50 OD; or about 0.5 and 25 OD; or between 1 and 10 OD; or between 1 and 3OD; or between 1 and 5 OD; or between 1 and 7.5 OD; or between 1 and 25 OD; or between 2.5 and 15 OD; or between 2 and 10 OD; or between 5 and 15 OD; or between 10 and 25 OD; or about 0.25 OD; or about 0.5 OD; or about 0.75 OD; or less than 2.5 OD; or less than 5 OD; or less than 7.5 OD; or less than 9 OD; or less than 10 OD; or about 1 OD; or about 2 OD; or about 2.5 OD; or about 3 OD; or about 4 OD; or about 5 OD; or about 6 OD; or about 7 OD; or about 7.5 OD; or about 8 OD; or about 9 OD; or about 10 OD; or about 11 OD; or about 12 OD; or about 12.5 OD; or about 15 OD; or about 16 OD; or about 17 OD; or about 18 OD; or about 19 OD; or about 20 OD; or about 25 OD; or about 30 OD; or about 35 OD; or about 40 OD; or about 50 OD.

[0026] In some embodiments of any of the methods described herein, the solution of photo-absorbing nanoparticles administered to the subject comprises nanoparticles (such as, for example, spherical nanoshells) in a concentration between about 1x109particles per mL and 1x1012particles per mL. In certain embodiments, the solution comprises less than 1.0 x1011particles per mL; or less than 7.5 x1010particles per mL; or less than 5 x1010particles per mL; or less than 1.0 x1010particles per mL; or less than 9.0 x109particles per mL; or less than 8.0 x109particles per mL; or between 1.0 x109and 1.0 x1011particles per mL; or between 2.0 x109and 5.0 x1010particles per mL; or between6ELUX-001-PCT2.0 x109and 1.0 x1010particles per mL; or between 3.0 x109and 8 x109particles per mL; or between 2.0 x109and 5 x109particles per mL; or between 5 x109and 8 x109particles per mL; or about 3.0 x109particles per mL; or about 3.5 x109particles per mL; or about 5.0 x109particles per mL; or about 5.5 x109particles per mL; or about 6.0 x109particles per mL; or about 6.5 x109particles per mL; or about 7.0 x109particles per mL; or about 7.5 x109particles per mL; or about 8.0 x109particles per mL; or about 8.5 x109particles per mL; or about 9.0 x109particles per mL; or about 9.5 x109particles per mL; or about 1.0 x1010particles per mL; or about 1.5 x1010particles per mL; or about 2.0 x1010particles per mL; or about 2.5 x1010particles per mL; or about 5.0 x1010particles per mL; or about 7.5 x1010particles per mL.

[0027] In various embodiments of the methods described herein, the pulses of near infrared light are administered at 10-15 J / cm2 (J / cm2); or about 8 J / cm2; or about 9 J / cm2; or about 10 J / cm2; or about 11 J / cm2; or about 12 J / cm2; or about 13 J / cm2; or about 14 J / cm2; or about 15 J / cm2.

[0028] In some embodiments of the methods described herein, the pulses of near infrared light are administered at a wavelength between 750 nm to 1100 nm; or about 750 nm; or about 800 nm; or about 810 nm; or about 1064 nm.

[0029] In some embodiments, the pulses of near infrared light are administered at a frequency of 1-1000 Hz; 1-10 Hz, 10-100 Hz, 100-1000 Hz; or about 1 Hz; or about 2 Hz; or about 3 Hz; or about 4 Hz; or about 5 Hz; or about 6 Hz; or about 7 Hz; or about 8 Hz; or about 9 Hz; or about 10 Hz; or about 20 Hz; or about 25 Hz; or about 50 Hz; or about 100 Hz.

[0030] In some aspects and embodiments of the disclosure, a system is provided for fat removal and / or skin tightening in accordance with any of the methods provided herein, wherein the system comprises a solution of photo-absorbing nanoparticles as provided herein; a means for injecting the solution into the target area; and a near infrared light source for delivering a beam of light to the target area. In one embodiment the system further includes a means for extracting melted fat from the target area.7ELUX-001-PCT

[0031] The terms “subject”, “individual” or “patient” as used herein may be used interchangeably refer to a vertebrate, preferably a mammal. In some embodiments a subject or patient according to the disclosure is a human.

[0032] Further scope, applicability and advantages will become apparent from the non-restrictive detailed description given hereinafter. It should be understood, however, that this detailed description, while indicating exemplary embodiments or aspects, is given by way of example only.BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 shows butter pads after exposure to laser with either rods, shells, or vehicle (water) only.

[0034] Figure 2 shows porcine tissue after treatment. Treatment with rods at 5 OD is on the left, and shells at 10 OD is on the right. Laser only was performed on the bottom middle region.

[0035] Figure 3 shows the injection angle into the porcine tissue.DETAILED DESCRIPTIONNanoparticles

[0036] In certain embodiments of the disclosure the nanoparticles of the methods and compositions described herein are nanoshells. Nanoshell nanoparticles used in some embodiments of this disclosure may include a metallic shell and a non-conducting, or dielectric core. These particles can be designed and constructed to absorb or scatter light at desired wavelengths. This “tunability” can be achieved by altering the ratio of the thickness of the metal shell to the non-conducting core.

[0037] The non-conducting core can be silica, but can be comprised of any dielectric material. Suitable dielectric materials include but are not limited to silicon dioxide, titanium dioxide, polymethyl methacrylate (PMMA), polystyrene, gold sulfide and macromolecules such as dendrimers. In some embodiments, core materials may be made of CdSe, CdS or GaAs.8ELUX-001-PCT

[0038] In various embodiment the nonconducting core is surrounded by a layer that is made of a conducting material. Generally, the conducting layer is metallic but it may also be an organic conducting material such as polyacetylene, doped polyanaline and the like. Suitable metals include the noble and coinage metals but any metal that can conduct electricity is suitable. Metals that are particularly well suited for use in shells include but are not limited to gold, silver, copper, platinum, palladium, lead, iron or the like. Gold and silver are preferred in some embodiments. Alloys or non-homogenous mixtures of such metals may also be used. In some embodiments, the exterior shell of the nanoshell can be comprised of gold.

[0039] In various aspects and embodiments of the present disclosure photo-absorbing nanoparticles and methods of using such are provided. In certain embodiments, the compositions and methods of the present disclosure combine near infrared (NIR) light exposure and a solution of photo-absorbing nanoparticles that may be injected into the treatment target in order to selectively heat fat in the target area.

[0040] As used herein, the term “photo-absorbing” with regard to nanoparticles refers to the ability of a nanoparticle to absorb light and, for example, release heat responsive to the absorbed light (such as by SPR as described below). The low power NIR light in certain embodiments harmlessly penetrates the skin and overlying tissue to be absorbed only by the photo-absorbing nanoparticles; and the excited nanoparticles generate heat, melting the fat and tightening the skin. The liquefied melted fat can be removed with a syringe or fine cannula, or in some embodiments the liquified fat is not removed and is left to be naturally broken down and removed by the subject’s body.

[0041] In many embodiments it is desirable that only regions into which the solution of gold nanorods has been injected are able to absorb the NIR wavelengths, which otherwise passes through the body virtually unnoticed. The amount of heating can be finely tuned by the nanorod dimensions, duration of exposure to the laser light and light intensity. Gold nanoparticles absorb light efficiently in the visible region due to coherent oscillations of metal conduction band electrons in strong resonance with visible frequencies of light, a phenomenon known as “surface plasmon resonance” or “SPR”. Photoexcitation of metal nanostructures results in the formation of a heated electron gas that cools rapidly, e.g., within 1 ps, by exchanging energy with the nanoparticle lattice. The nanoparticle lattice, in turn, rapidly exchanges energy with the surrounding medium9ELUX-001-PCTon the timescale of 100 ps, causing localized heating. This rapid energy conversion and dissipation can be achieved by using light radiation with a frequency that strongly overlaps the nanoparticle absorption band. Nanorods exhibit cylindrical symmetry, and simple changes in particle symmetry can significantly alter SPR characteristics.

[0042] The NIR absorption maximum of metal nanostructures can be modulated by changing their size, shape and aggregation. The effectiveness of photo-absorbing nanoparticles (such as nanoshells as described herein) as photothermal therapeutic agents is strongly dependent on their scattering and absorption cross-sections—large absorption cross sections with small scattering losses allow for photothermal therapy with a minimal laser dosage. In addition, the longitudinal surface plasmon wavelengths of nanoparticles may be preferably within the spectral range of 650-900 nm. Light irradiation in this region can penetrate more deeply into tissues and cause less photodamage than UV-visible irradiation. Therefore, the ability to tailor both scattering and absorption of GNRs with different longitudinal surface plasmon wavelengths is important for therapeutic applications.

[0043] As discussed in Huang and El-Sayed, Journal of Advanced Research (2010) 1, 13–28, doi: 10.1016 / j.jare.2010.02.002, the ratio of the scattering to absorption increases dramatically for larger size of particles. This fact can guide the choice of gold nanoparticles for biomedical applications. For imaging, lager nanoparticles are preferred because of higher scattering efficiency, whereas for photothermal therapy, smaller nanoparticles are preferred as light is mainly adsorbed by the particles and thus efficiently converted to heat for cell and tissue destruction. Compared to nanoshells, the use of gold nanorods enables effective treatment at three times lower laser intensity. This is because nanorods exhibit higher absorption efficiency than nanoshells with the SPR at the same wavelength.

[0044] For many of the embodiments of this disclosure, nanoshell particles may be designed to absorb infrared light at wavelengths where light is not significantly absorbed by human tissue. Human tissue is minimally absorptive in the ranges from 750 nm to 1100 nm, often referred to as the “water window” or “tissue optical window”. While solid gold nanoparticles and microparticles absorb light at wavelengths also absorbed by tissue, gold- coated nanoshell particles can be designed to absorb or scatter light within this “tissue optical window”, enabling new in vivo applications. More specifically, the10ELUX-001-PCTnanoshell particles used in the compositions and methods of the disclosure may include a thin gold shell, 10 to 30 nm thick, deposited on a solid silica (silicon dioxide) core.

[0045] Nanoparticles (e.g., nanoshells, gold nanoshells, and non-conducting core gold nanoshells) of the disclosure can be added to polymers during their preparation by methods well known in the art. Suitable polymers include polyethylene, polyvinyl alcohol (PVA), latex, nylon, teflon, acrylic, kevlar, epoxy, glasses and the like. Solubility of nanoparticles into polymers can be facilitated by functionalization of the nanoparticle surfaces with suitable molecules known to those of skill in the art. To prevent aggregation of the particles in a saline environment and to provide steric hindrance in vivo, a 5,000 molecular weight (MW) methoxy-polyethylene glycol (PEG) chain can be attached through a thiol moiety. The PEG coating in certain embodiments improves the stability of the nanoshell particles in an isotonic aqueous solution, and may also improve circulating half-life on administration.

[0046] Lasers and radiofrequency ablation devices may be used to thermally destroy tissue (such as adipose tissue) by delivery of energy at a rate in excess of the tissue’s ability to dissipate the energy through blood perfusion thermal diffusion. In addition, some lasers provide energy at wavelengths naturally absorbed by chromaphores within tissue or blood, using the properties of tissue or blood as a natural absorber to convert the light to thermal energy. The result is either thermal coagulation of cells or tissue thermal fixation and the disruption of the vasculature. In many aspects and embodiments, nanoparticles (such as nanoshells) are designed to absorb near-infrared energy, transducing it into heat via surface plasmon resonance.

[0047] In various embodiments, the nanoparticles of the disclosure are nanoshells (e.g., gold or silver nanoshells). In certain embodiments embodiments, the nanoparticles of the disclosure are core nanoshells (for example gold or silver nanoshells) such as described in, and or made by methods described in, for example, one or more of U.S. Patent Nos.6,344,272 and 6,685,986; and PCT Patent Application Nos.WO2012 / 027728, WO2013 / 169955, WO2015054493, and WO / 2018 / 112261 and in certain embodiments the nanoshells comprise a non-conducting core.

[0048] Certain nanoparticles, such as, for example, gold nanorods require use of cetyltrimethylammonium bromide (CTAB) to manufacture. There are concerns about the11ELUX-001-PCTtoxicity of CTAB (see for example the Santa Cruz Biotechnology Inc., MSDS for CTAB at https: / / datasheets.scbt.com / sc-278833.pdf). Thus, there may be risk that the use of CTAB could cause issues with the FDA and / or increased costs and efforts to remove CTAB and demonstrate the removal from each batch used. Moreover, CTAB is expensive and could result in an increase in the final cost of nanoparticles that require CTAB for manufacturing. Certain nanoshells (such as, e.g., certain gold nanoshells) as described herein can be manufactured without the use of CTAB. As such, in some embodiments, it may be useful to use nanoparticles that do not require CTAB for manufacturing.Delivery of Near Infrared Light

[0049] In various embodiments, the target area where the nanoparticles were administered is exposed to pulses of near infrared light; for example using a laser. The administration of light to activate the photo-absorbing nanoparticles is sometimes referred to herein as “light administration,” “light treatment,” “photo-therapy,” “laser treatment,” “laser therapy,” or the like. Generally the light / laser is applied topically to the skin above the target area where the nanoparticles had been administered. In various embodiments, the laser may be any one of many commercially available that are used for various dermatological and / or cosmetic purposes. One exemplary laser is the Palomar Vectus Laser. In some embodiments, the laser may be custom designed for a method of the disclosure. In certain embodiments, the target area is irradiated at a fluence of 1-60 J / cm2; or 1-20 J / cm2; or 5-15 J / cm2; or 10-15 J / cm2; or about 8 J / cm2; or about 9 J / cm2; or about 10 J / cm2; or about 11 J / cm2; or about 12 J / cm2; or about 13 J / cm2; or about 14 J / cm2; or about 15 J / cm2. In some embodiments, the near infrared light is administered with the laser wavelength between 750 nm to 1100 nm. In some embodiments the near infrared light is administered with the laser wavelength of about, e.g., 750 nm, 800 nm, 810 nm, or 1064 nm. Various repetition rates are may be used in different embodiments from continuous to pulsed, e.g., at 1-1000 Hz; 1-10 Hz, 10-100 Hz, 100-1000 Hz; or about 1 Hz; or about 2 Hz; or about 3 Hz; or about 4 Hz; or about 5 Hz; or about 6 Hz; or about 7 Hz; or about 8 Hz; or about 9 Hz; or about 10 Hz; or about 20 Hz; or about 25 Hz; or about 50 Hz; or about 100 Hz. While some energy is reflected, it is an advantage of the subject matter described herein is that a substantial amount of energy is absorbed by particles, with a lesser amount absorbed by skin.12ELUX-001-PCT

[0050]

[0095] To enable tunable destruction and / or melting / liquification of target tissues, light-absorbing nanoparticles may be utilized in conjunction with a laser or other excitation source of the appropriate wavelength. The laser light may be applied continuously or in pulses with a single or multiple pulses of light. The intensity of heating and distance over which photothermal damage will occur are controlled by the intensity and duration of light exposure. In some embodiments, pulsed lasers are utilized in order to provide localized thermal destruction. In some such embodiments, pulses of varying durations are provided to localize thermal damage regions to within 0.05, 0.1, 0.5, 1, 2, 5, 10, 20, 30, 50, 75, 100, 200, 300, 500, 1000 microns of the particles. Pulses may in some embodiments be femtoseconds, picoseconds, microseconds, or milliseconds in duration. In some embodiments, the peak temperature realized in tissue from nanoparticle heating is at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, or 500 degrees Celsius. Examples of non-invasive, real-time techniques to map surface and subsurface temperatures include, but are not limited to, infrared cameras to detect thermal radiation emitted from the skin surface, producing 2D / 3D thermograms of temperature distribution; thin-film thermocouples or flexible resistance temperature detector arrays affixed to the skin; photoacoustic thermometry, and optical nanothermometry.

[0051] The following are exemplary temperatures that may be considered for some various aspects and embodiments of the present disclosure:Adipocyte Thermal Melting / Destruction Treatment Temperatures:42-50°C: Fat cell membrane disruption and melting begins 70-80°C : Complete adipocyte destructionSkin Tightening Treatment Temperatures:55-65°C: Immediate collagen contraction begins65-75°C: Collagen denaturation rangeTemperature Comparison: Fat vs. Skin TighteningFat Reduction: 40-60°CLower threshold than skin tightening13ELUX-001-PCTLonger exposure times tolerated (10-30 seconds)Fat cells are more thermally sensitive than collagenSkin Tightening: 50-70°CHigher temperatures requiredShorter exposure times (0.5-6 seconds)Collagen requires more energy to denature

[0052] “Local temperature” or “internal temperature” refers to the temperature at or around the location of the administered photo-absorbing nanoparticles. “Surface temperature” or “skin surface temperature” refers to the temperature at the surface of the skin above the location where the photo-absorbing nanoparticles are administered.

[0053] As used herein “sustained temperature” is a local or surface temperature achieved in embodiments of the methods that are sustained (within about 15%; or about 10%; or about 5%) in a particular treatment area for a 0.1-90 second; or 0.5-60 second; or 0.5-30 second; or 0.5-20 second; or 0.5-10 second; or 0.5-9 second; or 0.5-8 second; or 0.5-7 second; or 0.5-6 second; 0.5-5 second; or 0.5-4 second; or 0.5-3 second; or 1-10 second; or 2-10 second; or 3-10 second; or 5-10 second; or 3-6 second; or 5-60 second; or 10-60 second; or 1-30 second; or 2-30 second; or 3-30 second; or 4-30 second; or 5-30 second; or 10-30 second; or 15-30 second; or 20-30 second; or about 0.5 second; or about 0.75 second; or about 1 second; or about 2 second; or about 3 second; or about 4 second; or about 5 second; or about 7.5 second; or about 10 second; or about 12.5 second; or about 15 second; or about 20 second; or about 25 second; or about 30 second; or about 40 second; or about 45 second; or about 60 second; or about 90 second period of time.Maximum sustained temperature means the highest sustained temperature achieved in a particular procedure.

[0054] In some aspects and embodiments of the disclosure, the methods involve achieving a sustained temperature (or maximum sustained temperature) in the internal (local) treatment tissue / area of 40-75 °C; or 40-70 °C; or 40-65 °C; or 40-66 °C; or 40-55 °C; or 40-50 °C; or 40-45 °C; or 42-75 °C; 42-70 °C; or 42-65 °C; or 42-60 °C; or 42-55 °C; or 42-50 °C; or 45-75 °C; 45-70 °C; or 45-65 °C; or 45-60 °C; or 45-55 °C; or 45-50 °C; or 50-75 °C; 50-70 °C; or 50-65 °C; or 50-60 °C; or 50-55 °C; or 55-7514ELUX-001-PCT°C; 55-70 °C; or 55-65 °C; or 55-60 °C; or about 40 °C; or about 42 °C; or about 45 °C; or about 50 °C; or about 55 °C; or about 60 °C; or about 65 °C; or about 70 °C; or about 75 °C.

[0055] Regardless of indication, use and administration route in various embodiments localized internal temperatures above about 70-90°C and / or surface skin temperatures above about 40-48°C may result in a risk of burns, tissue necrosis and / or permanent damage. In order to reduce risk of adverse side effects or damage or to achieve a desired cosmetic effect , in some embodiments the sustained temperatures may be even less than 70-90°C internally and / or 40-48 °C on the skin surface. In some embodiments the sustained internal temperature may be below 70 or 65 °C to avoid direct complete fat ablation. Accordingly, in some embodiments the methods are performed such that the sustained local temperature (or maximum sustained local temperature) is below 85 °C; or below 80 °C; or below 75 °C; or below 70 °C; or below 69 °C; or below 68 °C; or below 65 °C; or below 64 °C; or below 63 °C; or below 62 °C; or below 61 °C; or below 60 °C; or below 59 °C; or below 58 °C; or below 57 °C; or below 56 °C; or below 55 °C; or below 54 °C; or 53 below °C; or below 52 °C; or below 51 °C; or below 50 °C throughout the procedure. In some situations skin surface temperatures at around 42-45 °C can cause skin burning. Accordingly in certain embodiments the surface skin temperature is below 48 °C; or below 47 °C; or below 46 °C; or below 45 °C; or below 44 °C; or below 43 °C; or below 42 °C; or below 41 °C; or below 40 °C throughout the procedure. In some embodiments, the skin surface may be cooled with a cooling device, a wet cloth, water, ice or the like to ensure the skin surface remains below the maximum temperature.Indications / Target Fat Tissues and Areas.

[0056] In various aspects and embodiments, the methods and compositions of the disclosure can be used in any procedure designed to reduce and or remove fat in a subject.

[0057] In certain embodiments of the disclosure, the target fat is abdominal fat; for example, fat in the flanks and periumbilical region. In some embodiments, the target fat is abdominal fat, and the methods / compositions are used in a liposuction procedure. In some embodiments, the target fat is abdominal fat, and the methods / compositions are used in a liposuction procedure; in which the photo-absorbing nanoparticles are15ELUX-001-PCTadministered to abdominal fat in the subject, pulses of near infrared light are administered to the surface of the skin above the abdominal fat; and the melted / liquified fat is removed by suction or aspiration. In some embodiments, the target fat is abdominal fat; for example fat in the flanks and periumbilical region, and the methods involve administering photo-absorbing nanoparticles as described herein followed by administration of pulses of near infrared light, but the melted / liquified fat is not removed, and instead is left to be re-absorbed and removed by the body naturally. In some embodiments, the fat is abdominal fat and the methods / compositions are used in an abdominoplasty procedure (e.g., abdominoplasty with liposuction-assisted contouring). In some embodiments of these procedures, relatively large volumes of nanoparticle-containing solution may be used, for example volumes greater than 500 ml.

[0058] In some embodiments, the target fat is submental fat. In related embodiments, the compositions / methods of the disclosure can be useful for a subject desiring a reduction in submental fat, and / or the reduction of what is often referred to as double chin. In some embodiments, the compositions and methods of the disclosure are used to improve the appearance of convexity or fullness associated with submental fat. In some embodiments, the compositions and methods of the disclosure are used to improve the appearance of moderate to severe convexity or fullness associated with submental fat in an adult. In some embodiments relating to targeting submental fat, the solution with photo-absorbing nanoparticles is administered subcutaneously by injection, for example injections on a injection grid (such as a standard 1 cm grid). In some embodiments, the injection pattern evenly covers the central convex submental area, with slightly greater density of injections in the midline and tapering laterally. In some embodiments, a needle that is about 30-guage and about ½ inch is used. In some embodiments, about 0.2 mL of the photo-absorbing nanoparticles containing solution is delivered in each injection; or in related embodiments 0.1-0.5 mL; or 0.15-0.25 mL; or about 0.15 mL; or about 0.175 mL; or about 0.19 mL; or about 0.21 mL; or about 0.22 mL; or about 0.23 mL; or about 0.24 mL; or about 0.25 mL; or about 0.3 mL; or about 0.5 mL of the photo-absorbing nanoparticles containing solution is delivered in each injection. In some embodiments, a treatment session involves about 20 total injections; or about 10-50 injections; or about 10-40 injections; or about 10-30 injections; or about 15-25 injections; or about 10 injections; or about 12 injections; or about 15 injections; or about 17 injections; or about 18 injections; or about 19 injections; or about 21 injections; or about 22 injections; or16ELUX-001-PCTabout 23 injections; or about 24 injections; or about 25 injections; or about 26 injections; or about 27 injections; or about 30 injections of the photo-absorbing nanoparticles containing solution. In some embodiments a treatment session involves injecting a total volume of photo-absorbing nanoparticles containing solution (for example in multiple injections such as described herein) of 0.5- 20 mL; or 0.5-10 mL; or 0.5-5 mL; or 1-25 mL; or 1-20 mL; or 1-10 mL; or 1-5 mL; or 2-6 mL; or 2-10 mL; or 3-10 mL; or 5-10 mL; or 6-10 mL; or 7-10 mL; or 8-10 mL; or 2-8 mL; or 2-6 mL; or 3-5 mL; or about 1 mL; or about 2mL; or about 3 mL; or about 4 mL; or about 5 mL; or about 6 mL; or about 7 mL; or about 8 mL; or about 9 mL; or about 10 mL. In some embodiments only one treatment session is used; in some embodiments two treatment sessions are used; in some embodiments three treatment sessions are used; in some embodiments four treatment sessions are used; in some embodiments five treatment sessions are used; in some embodiments six treatment sessions are used; in some embodiments seven treatment sessions are used; in some embodiments eight treatment sessions are used; in some embodiments nine treatment sessions are used; in some embodiments 10 treatment sessions are used; in some embodiments the maximum number if treatment sessions is 10 or less; or 9 or less; or 10 or less; or 8 or less; or 7 or less; or 6 or less; or 5 or less; or 4 or less; or 3 or less. In certain related embodiments that may use similar administration amounts and routes as submental fat treatment; the target fat is one or more selected from the group consisting of “brassiere-line” fat (i.e. localized fat in the upper chest / under-arm area), foot fat (small fat deposits in the foot), gluteotrochanteric region (outer thigh / buttock-hip junction) fat, lipomatous tumors (benign lipomas), HIV / HAART-associated buccal fat pad lipodystrophy fat, and paradoxical adipose hyperplasia fat.

[0059] As used herein, the term “treatment session” means a treatment session that involves a round of administration of photo-absorbing nanoparticles and light / laser therapy to activate the nanoparticles in a subject.

[0060] In some embodiments, the methods and compositions of the disclosure cause skin tightening in a subject. In certain embodiments, when skin tissues are heated to specific temperatures (for example using photo-absorbing nanoparticles and light treatment / laser therapy such as described herein), hydrogen bonds and cross-links within the collagen helix break causing the collagen fibers to shrink and contract immediately, pulling the surrounding extracellular matrix tighter. In certain embodiments, this can17ELUX-001-PCTcause a visible effect of an acute tightening of the skin. Longer term, a wound-healing cascade and neocollagenesis may occur which is caused by fibroblasts in and / or aroundthe dermis being activated, releasing growth factors such as TGF- growthfactor beta). Over weeks to months, fibroblasts synthesize new collagen (types I and III) and elastin. This process is called neocollagenesis and leads to thicker, more organized dermal matrix. The gradual remodeling phase contributes to the more sustained tightening effect seen months after treatment. Accordingly, in some embodiments the skin tightening effect occurs in two phases: immediate contraction (visible right after treatment) and progressive tightening over 3-6 months as new collagen forms and matures (i.e, acutely shrink skin tissue already present and also stimulate the skin to rebuild itself with stronger, more elastic connective tissue). In some embodiments, skin tightening is achieved using procedures described herein for fat melting / liquification and may involve subcutaneous administration of photo-absorbing nanoparticles. In other embodiments, instead of, or in addition to, subcutaneous administration skin tightening applications may involve administering the photo-absorbing nanoparticles more shallowly into the dermis (intradermal or subdermal) above the subcutaneous tissue, for example, into the superficial dermis (or Papillary dermis, 1-2mm), deep dermis (or reticular dermis; 2-4mm; in certain embodiments a primary target for skin tightening), dermal-subcutaneous junction (4-6mm), and / or subcutaneous fibrous septae (6-15mm). In certain embodiments, skin tightening applications may be performed at higher temperatures and / or shorter temperature intervals than certain fat melting embodiments, for example, as described elsewhere herein.Adipose Tissue Melting and / or Ablation and / or Removal

[0061] Liposuction evolved from work in the late 1960s from surgeons in Europe using primitive curettage techniques which were largely ignored, as they achieved irregular results with significant morbidity and bleeding. Modern liposuction first burst on the scene in a presentation by the French surgeon, Dr Yves-Gerard Illouz, in 1982. The "Illouz Method" featured a technique of suction-assisted lipolysis after tumesing or infusing fluid into tissues using blunt cannulas and high-vacuum suction and demonstrated both reproducible good results and low morbidity. During the 1980s, many United States surgeons experimented with liposuction, developing variations, and achieving mixed results. Most commonly, liposuction is performed on the abdomen and18ELUX-001-PCTthighs in women, and the abdomen and flanks in men. According to the American Society for Aesthetic Plastic Surgery, liposuction was the most common plastic surgery procedure performed in 2006 with 403,684 patients.

[0062] Traditional liposuction relies on two techniques. The first technique employs a sharp, relatively large diameter (3mm-5mm) cannula that is manually manipulated to mechanically break fat down and while applying suction to remove the separated fat. A variation of this vacuum assisted technique is a mechanically powered cannula that reduces the surgeon's fatigue during large surface area liposuction procedures.

[0063] The second technique utilizes ultrasonic waves via a vibrating cannula. This technique is mechanical in its nature and significantly reduces the surgeon's fatigue factor. This technique induces the same or worse mechanical trauma to the tissues. Both techniques require significant amounts of fluid, known as a "tumescent solution," to be injected into the body to emulsify the fat, facilitating the removal of large volumes of fat while reducing blood loss and delivering a local anesthetic (lidocaine) to provide post-operative pain relief. While generally safe, lidocaine can be toxic, leading to serious complications, and even death.

[0064] A problem with the probes used in existing liposuction procedures is the generation of significant amounts of heat at the distal tip of the probe, which can exceed the temperature required for melting the fatty tissue. This excess heat can result in burning of tissue, damaging muscles or blood vessels, and even penetrating membranes such as the skin or the peritoneum that covers most of the intra-abdominal organs.

[0065] Alternative methods have been disclosed which exploit laser energy to remove unwanted fat. U.S. Pat. Nos.6,605,080 and 7,060,061 issued to Altshuler, et al. represent an alternative approach in which laser energy is externally applied to the skin to heat and melt fat tissues in epidermis and subcutaneous layers below. These patents disclose the use of near infrared radiation to heat-liquefy fat cells, after which the lipid pool is removed from the subcutaneous area by aspiration. Because of the considerable heat generation that results from the techniques, e.g., up to 70 °C, at or in the fat tissue, a special cooling mechanism must be in place to prevent potential temporary skin damage or permanent scarring, with permanent scarring occurring primarily in the dermis. These19ELUX-001-PCTmethods present other limitations and potential adverse thermal effects on tissue above the lipid-rich tissue under treatment, including blistering, peeling, and depigmentation.

[0066] U.S. Patent No.8,430,919 of Bornstein discloses a lipolysis method in which the skin over the target site is optically irradiated with two different wavelengths of light, one in the near infrared (MR) region, the other in the infrared range, to modulate biochemical processes of adipocytes in the target site. In order to achieve the desired degree of fat removal, the duration of the treatment must be fairly long, from one to two hours, during which the patient must remain virtually motionless. Unless a sedative or general anesthesia has been administered to calm the patient, physical and psychological discomfort can ensue. NIR (700-950 nm) is preferable to other types of light for therapeutic use in biological systems because NIR light can pass through blood and tissue to depths of several inches. However, very few organic chromophores absorb in this region, and even fewer are capable of converting the absorbed energy into a chemical or thermal response that can be used to trigger drug release. A few years ago, gold nanostructures (shells, particles, rods, and cages) emerged as useful agents for photothermal therapy after they were shown to have strong absorption in the NIR region (four to five times higher than conventional photo-absorbing dyes) as well as tunable optical resonances. The strong absorption enables effective laser therapy at relatively low laser energies, rendering such therapy methods minimally invasive.

[0067] The present disclosure provides new methods (for example using non-conducting core gold nanoshells) for fat melting or ablation and skin tightening that in certain embodiments may have advantages over previously used methods, such as advantages in safety and expense.

[0068] In various aspects and embodiments of the methods of the disclosure, it is desirable that the combination of nanoparticles and light (laser) are administered such as to remove, or assist in the removal of, fat and / or to cause skin tightening in a subject. In many embodiments the methods are conducted such as to cause ablation and / or melting / liquification of fat in the treated area. “Ablation” as used herein in the context of photothermal therapy refers to the controlled removal or alteration of tissue through energy application, typically via laser or heat. In its broadest sense, ablation encompasses outcomes that provide the complete destruction of tissue, where the targeted tissue is vaporized, carbonized, or otherwise fully eradicated (e.g., in tattoo removal or lesion20ELUX-001-PCTablation, achieving temperatures >100°C for vaporization); and also structural destruction, where the tissue's integrity or architecture is disrupted without complete removal, such as by melting, coagulation, or denaturation (e.g., collagen melting at 60– 70°C in skin rejuvenation or fat liquefaction in laser lipolysis). The specific outcome depends on the energy parameters, tissue type, and therapeutic goal, with precise temperature control (monitored via methods like IR thermography or invasive probes) ensuring safety and efficacy. “Direct complete ablation” refers to treatments having an intensity and duration such that the tissue becomes completely eradicated. In certain embodiments, the compositions and methods of the disclosure involve using a more gentle intensity and duration such that results in target fat melting / liquifying rather than complete eradication. In fat melting / liquifying the fat tissue is converted from a solid to liquid state, but still exists in the subject immediately after the treatment. In certain embodiments, melting / liquifying may be advantageous over complete ablation in that it is less likely to cause injury to immediately surrounding tissues and may result in a shorter and / or easier recovery process. In cases where melting / liquifying is used, the melted fat can be removed by aspiration and / or liposuction from the subject; and the removal may be easier, more complete, and / or less invasive than removing the fat without the melting / liquifying pre-treatment. Alternatively, when melting / liquifying is used the melted fat can be left in the subject (i.e., not removed by aspiration, etc) and the subject’s body will subsequently reabsorb and remove the liquid fat.Administration

[0069] As used herein, the term “administer” an agent as described herein can include any route of introducing or delivering. Administration can be carried out by any suitable route, including oral, topical, intravenous, subcutaneous, transcutaneous, transdermal, intramuscular, intra-joint, parenteral, intra-arteriole, intradermal, intraventricular, intracranial, intraperitoneal, intralesional, intranasal, rectal, vaginal, by inhalation, via an implanted reservoir, parenteral (e.g., subcutaneous, intravenous, intramuscular, intra-articular, intra-synovial, intrasternal, intrathecal, intraperitoneal, intrahepatic, intralesional, and intracranial injections or infusion techniques), and the like.

[0070] The term “subcutaneous tissue” as used herein refers to the layer of tissue located immediately beneath the dermis in the skin's anatomical structure. In this context, it specifically denotes the hypodermis (also called the subcutaneous layer or superficial21ELUX-001-PCTfascia), which is the deepest layer of the skin, situated directly below the dermis and above deeper structures like muscle or bone. The hypodermis is the primary site of fat storage in the body, and its adipocyte-rich composition makes it a suitable target for procedures aiming to disrupt or reduce fat deposits.

[0071] The term “subcutaneous administration” as used herein refers to delivery of an agent (such as nanoshells, for example, a solution comprising nanoshells) directly into the subcutaneous tissue. Often, or generally, subcutaneous administration is performed by subcutaneous injection. The term “subcutaneous infiltration” as used herein is an example of subcutaneous administration and / or subcutaneous injection that involves relatively large volumes (e.g., more than 10 mL; or more than 20 mL; or more than 25 mL; or more than 50 mL, or more than 75 mL) of fluid being administered.Subcutaneous infiltration in various aspects and embodiments may be carried out using a needle, canula, or the like. In many embodiments, it is desired that subcutaneous administration and / or subcutaneous infiltration is strictly subcutaneous as intradermal administration / infiltration may in some circumstances cause skin injury, and intramuscular administration / infiltration can in certain circumstances increase the risk of systemic toxicity, bleeding, or trauma to deeper structures. Subcutaneous administration (including subcutaneous injection and subcutaneous infiltration) as contemplated herein does not include topical or intravenous administration.

[0072] The term “subdermal administration” as used herein means administration of an agent (such as nanoshells, for example, a solution comprising nanoshells) directly into the layer of tissue immediately beneath the dermis, but not extending into the subcutaneous tissue. The injected material is placed in the fibrous connective tissue that anchors the skin to the underlying fat and muscle. The term "subdermal" is sometimes used interchangeably with "intradermal" in cosmetics, though strictly, subdermal implies just below the dermis, at or above the dermis-hypodermis junction.

[0073] In some embodiments, nanoparticles (such as gold nanoshells) may be administered in a tumescent fluid. Tumescent fluid is a formulated solution that is injected (and / or infiltrated) into the subcutaneous fat layer to facilitate, for example, liposuction and / or related procedures. The term tumescent comes from the Latin tumescere, meaning “to swell,” reflecting the swelling and firming of tissues that occurs when the solution is infused. This technique was pioneered by Dr. Jeffrey Klein in the22ELUX-001-PCT1980s and remains a cornerstone of current liposuction. Tumescent fluid may include one or more of (1) a carrier solution (diluent), (2) a local anesthetic, (3) a vasoconstrictor, and (4) other additives (such as for example, nanoparticles). The carrier solution (diluent) may in many embodiments be normal saline or lactated Ringer’s solution and in various embodiments may provide bulk volume for hydrodissection and tissue expansion. In some embodiments, for example embodiments that involve relatively low volumes (e.g., less than 10 mL; or less than 5 mL, etc) of tumescent fluid, it may be that the tumescent fluid is not intended to provide bulk volume for hydrodissection and tissue expansion, but rather, to provide a vehicle for the other ingredients of the fluid. The local anesthetic is most commonly lidocaine but can be any suitable local anesthetic. In various embodiments, the local anesthetic ensures analgesia of the subcutaneous tissue, and may allow liposuction or other procedures to be performed under local, rather than general, anesthesia. The vasoconstrictor is often epinephrine and may act to induce localized vasoconstriction, minimizes bleeding and / or reduces systemic absorption of lidocaine or other ingredients in the tumescent fluid (such as nanoparticles if included). In some embodiments, some, but not all, of the tumescent fluid used in a procedure includes nanoparticles such as disclosed herein, and the remaining tumescent fluid used does not include nanoparticles. For example, in some embodiments, a first amount of tumescent fluid may include nanoparticles, and subsequent amounts of tumescent fluid may not include nanoparticles. In some embodiments, tumescent fluid that includes nanoparticles may be administered, followed by laser / near infrared (NIR) light treatment such as described herein; and after the laser treatment tumescent fluid that does not include nanoparticles may be used, for example to assist in aspiration of fat.

[0074] In some embodiments (for example, embodiments where target fat is abdominal fat), the photo-absorbing nanoparticles are administered in a tumescent solution wherein the volume of the tumescent solution is 100 – 5,000 mL; or 500 -3,000 mL; or 500-2,000 mL; or 500-1,500 mL; or 500-1,000 mL; or 1,000 – 2,000 mL; or 1,000 – 3,000 mL; or 1,000 – 5,000 mL; or about 500 mL; or about 1,000 mL; or about 1,500 mL; or about 2,000 mL; or about 2,500 mL; or about 3,000 mL; or about 4,000 mL; or about 5,000 mL.

[0075] In some embodiments (for example, embodiments where target fat is abdominal fat), the photo-absorbing nanoparticles are administered in 1000mL of23ELUX-001-PCTtumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1000mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1000mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1000mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 100mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 100mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 100mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 100mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 200mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 200mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 200mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 200mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 300mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 300mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 300mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 300mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 400mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 400mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 400mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 400mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 500mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 500mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 500mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 500mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 600mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 600mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 600mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 600mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 700mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 700mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 700mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD;24ELUX-001-PCTor 700mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 800mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 800mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 800mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 800mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 900mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 900mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 900mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 900mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1100mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1100mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1100mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1100mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1200mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1200mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1200mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1200mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1300mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1300mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1300mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1300mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1400mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1400mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1400mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1400mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1500mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1500mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1500mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1500mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1600mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1600mL of tumescent solution,25ELUX-001-PCTwherein said nanoparticles are at a concentration of 2.5 OD; or 1600mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1600mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1700mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1700mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1700mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1700mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1800mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1800mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1800mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1800mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 1900mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 1900mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 1900mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 1900mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2000mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2000mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2000mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2000mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2100mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2100mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2100mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2100mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2200mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2200mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2200mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2200mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2300mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2300mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2300mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2300mL of tumescent solution, wherein said nanoparticles are26ELUX-001-PCTat a concentration of 10 OD; or 2400mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2400mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2400mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2400mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2500mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2500mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2500mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2500mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2600mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2600mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2600mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2600mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2700mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2700mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2700mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2700mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2800mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2800mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2800mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2800mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 2900mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 2900mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 2900mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 2900mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3000mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3000mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3000mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3000mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3100mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3100mL of tumescent solution, wherein said nanoparticles are at a concentration27ELUX-001-PCTof 2.5 OD; or 3100mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3100mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3200mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3200mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3200mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3200mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3300mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3300mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3300mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3300mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3400mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3400mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3400mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3400mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3500mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3500mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3500mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3500mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3600mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3600mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3600mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3600mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3700mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3700mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3700mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3700mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 3800mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3800mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3800mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3800mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or28ELUX-001-PCT3900mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 3900mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 3900mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 3900mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4000mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4000mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4000mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4000mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4100mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4100mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4100mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4100mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4200mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4200mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4200mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4200mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4300mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4300mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4300mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4300mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4400mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4400mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4400mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4400mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4500mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4500mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4500mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4500mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4600mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4600mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4600mL of tumescent29ELUX-001-PCTsolution, wherein said nanoparticles are at a concentration of 5 OD; or 4600mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4700mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4700mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4700mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4700mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4800mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4800mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4800mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4800mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD; or 4900mL of tumescent solution, wherein said nanoparticles are at a concentration of 1.25 OD; or 4900mL of tumescent solution, wherein said nanoparticles are at a concentration of 2.5 OD; or 4900mL of tumescent solution, wherein said nanoparticles are at a concentration of 5 OD; or 4900mL of tumescent solution, wherein said nanoparticles are at a concentration of 10 OD.

[0076] “Systemic administration” refers to the introducing or delivering to a subject an agent via a route which introduces or delivers the agent to extensive areas of the subject's body (e.g., greater than 50% of the body), for example through entrance into the circulatory or lymph systems, and affecting multiple organs or systems. By contrast, “local administration” refers to the introducing or delivery to a subject an agent via a route which introduces or delivers the agent to the area or area immediately adjacent to the point of administration and does not introduce the agent systemically in a therapeutically significant amount. For example, locally administered agents are easily detectable in the local vicinity of the point of administration but are undetectable or detectable at negligible amounts in distal parts of the subject's body. In many aspects and embodiments of the disclosure subcutaneous administration (including subcutaneous injection and subcutaneous infiltration) is an example of local administration.Administration includes self-administration and the administration by another.

[0077] In various aspects and embodiments, the nanoparticles (e.g., gold nanoshells) are administered by injection. In certain embodiments the nanoparticles (e.g., gold30ELUX-001-PCTnanoshells) are administered by injection into target areas having adipose tissue. In some the nanoparticles (e.g., gold nanoshells) are administered by subcutaneous injection.

[0078] “Pharmaceutically acceptable carrier” (sometimes referred to as a “carrier”) refers to a carrier or excipient that is useful in preparing a pharmaceutical or therapeutic composition that is generally safe and non-toxic and includes a carrier that is acceptable for veterinary and / or human pharmaceutical or therapeutic use. The terms “carrier” or “pharmaceutically acceptable carrier” can include, but are not limited to, phosphate buffered saline solution, water, emulsions (such as an oil / water or water / oil emulsion) and / or various types of wetting agents. As used herein, the term “carrier” encompasses, but is not limited to, any excipient, diluent, filler, salt, buffer, stabilizer, solubilizer, lipid, stabilizer, or other material well known in the art for use in pharmaceutical formulations and as described further herein.

[0079] The term “modulate,” “modulates,” or “modulation” as used herein refers to enhancement (e.g., an increase) or inhibition (e.g., a decrease) in the specified level or activity.

[0080] The term “enhance” or “increase” refers to an increase in the specified parameter of at least about 1.25-fold, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 8-fold, 10-fold, twelve-fold, or even fifteen-fold and / or can be expressed in the enhancement and / or increase of a specified level and / or activity of at least about 1%, 5%, 10%, 15%, 25%, 35%, 40%, 50%, 60%, 75%, 80%, 90%, 95% or more.

[0081] The use of the terms “a” and “an” and “the” are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0082] Unless specifically stated or obvious from context, as used herein the term “or” is understood to be inclusive and covers both “or” and “and”.

[0083] The term “and / or” where used herein is to be taken as specific disclosure of each of the specified features or components with or without the other.31ELUX-001-PCT

[0084] The terms “comprising”, “having”, “including”, and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to”) unless otherwise noted. The term “consisting of” is to be construed as close-ended.

[0085] The term “between” as used herein with regard to a range of values contemplates and includes the value at each of the ends of the recited range; for example, “between 1 and 10” contemplates and includes 1 as well as 10 in addition to each value that is between 1 and 10.

[0086] As used herein, the term “dosage period” refers to the period of time between dosage administration of a drug to a subject.

[0087] As used herein, the transitional phrase “consisting essentially of” (and grammatical variants) is to be interpreted as encompassing the recited materials or steps and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. Thus, the term “consisting essentially of” as used herein should not be interpreted as equivalent to “comprising.”

[0088] The term “therapeutically effective amount” or “effective amount,” as used herein, refers to that amount of a composition, compound, or agent of this invention that imparts a modulating effect, which, for example, can be a beneficial effect, to a subject afflicted with a disorder, disease or illness, including improvement in the condition of the subject (e.g., in one or more symptoms), delay or reduction in the progression of the condition, prevention or delay of the onset of the disorder, and / or change in clinical parameters, disease or illness, etc., as would be well known in the art. For example, a therapeutically effective amount or effective amount can refer to the amount of a composition, compound, or agent that improves a condition in a subject by at least 5%, e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100%.

[0089] In the context of photothermal therapy using NPs, a therapeutically effective amount refers to the specific quantity of NPs (e.g., gold nanoshells administered via subcutaneous injection into the hypodermis) that, when combined with controlled laser irradiation at a specified intensity, produces sufficient localized heating to achieve the desired cosmetic outcome without causing adverse effects such as burns, scarring, or32ELUX-001-PCTexcessive tissue damage. This amount is tailored to impart a modulating effect such as a beneficial alteration in the targeted tissue (e.g., fat reduction, skin rejuvenation, or tattoo removal).

[0090] “Inhibit” or “reduce” or grammatical variations thereof as used herein refers to a decrease or diminishment in the specified level or activity of at least about 1, 5, 10, 15%, 25%, 35%, 40%, 50%, 60%, 75%, 80%, 90%, 95% or more. In particular embodiments, the inhibition or reduction results in little or essentially no detectible activity (at most, an insignificant amount, e.g., less than about 10% or even 5%).

[0091] “Treat,” “treating” and similar terms as used herein in the context of treating a subject refer to providing medical and / or surgical management of a subject. Treatment may include, but is not limited to, administering an agent or composition (e.g., a pharmaceutical composition) to a subject. Treatment is typically undertaken in an effort to alter the course of a disease (which term is used to indicate any disease, disorder, syndrome, or undesirable condition warranting or potentially warranting therapy) in a manner beneficial to the subject. The effect of treatment may include reversing, alleviating, reducing severity of, delaying the onset of, curing, inhibiting the progression of, and / or reducing the likelihood of occurrence or recurrence of the disease or one or more symptoms or manifestations of the disease. A therapeutic agent may be administered to a subject who has a disease or is at increased risk of developing a disease relative to a member of the general population. In some embodiments a therapeutic agent may be administered to a subject who has had a disease but no longer shows evidence of the disease. The agent may be administered e.g., to reduce the likelihood of recurrence of evident disease. A therapeutic agent may be administered prophylactically, i.e., before development of any symptom or manifestation of a disease. “Prophylactic treatment” refers to providing medical and / or surgical management to a subject who has not developed a disease or does not show evidence of a disease in order, e.g., to reduce the likelihood that the disease will occur, delay the onset of the disease, or to reduce the severity of the disease should it occur. The subject may have been identified as being at risk of developing the disease (e.g., at increased risk relative to the general population or as having a risk factor that increases the likelihood of developing the disease.33ELUX-001-PCTSELECTED SPECIFIC EMBODIMENTS

[0092] In addition to the aspects and embodiments disclosed elsewhere herein, the following particular embodiments are specifically contemplated.1. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area.2. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise at least one non-conducting core layer and at least one conducting shell layer.3. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have at least one axial dimension (diameter / length) longer that 100 nm.4. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have an aspect ratio in the range of 1:1 to 1:2.5. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles are substantially spherical.6. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles34ELUX-001-PCTinto adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise a core and a shell encapsulating the core, wherein said shell comprises at least one atomic element not included in the core.7. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area.8. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise at least one non-conducting core layer and at least one conducting shell layer.9. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have at least one axial dimension (diameter / length) longer that 100 nm.10. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have an aspect ratio in the range of 1:1 to 1:2.11. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles are substantially spherical.12. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area35ELUX-001-PCTof skin overlying the target area; wherein said nanoparticles comprise a core and a shell encapsulating the core, wherein said shell comprises at least one atomic element not included in the core.13. The method of any one of the previous embodiments, wherein the nanoparticles have an aspect ratio of about 1:1.14. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells.15. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a non-conducting core that comprises dielectric materials and / or semiconductor materials.16. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a non-conducting core that comprises one or more dielectric materials selected from the group consisting of silicon dioxide (silica), titanium dioxide, polymethyl methacrylate (PMMA), polystyrene, gold sulfide and macromolecules such as dendrimers.17. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a non-conducting core that comprises silicon dioxide (silica).18. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a conducting shell layer comprising one or more metals selected from the group consisting of gold, silver, copper, platinum, palladium, lead, and iron. 19. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a conducting shell layer comprising one or more metals selected from the group consisting of gold and silver.20. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a conducting shell layer comprising gold.21. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a conducting shell layer comprising silver.36ELUX-001-PCT22. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a non-conducting core that comprises one or more dielectric materials selected from the group consisting of silicon dioxide (silica), titanium dioxide, polymethyl methacrylate (PMMA), polystyrene, gold sulfide and macromolecules such as dendrimers; and having a conducting shell layer having23. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a non-conducting core that comprises one or more dielectric materials selected from the group consisting of silicon dioxide (silica), titanium dioxide, polymethyl methacrylate (PMMA), polystyrene, gold sulfide and macromolecules such as dendrimers; and having a conducting shell layer comprising one or more metals selected from the group consisting of gold, silver, copper, platinum, palladium, lead, and iron. 24. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a non-conducting core that comprises silicon dioxide (silica) and having a conducting shell layer comprising one or more metals selected from the group consisting of gold and silver.25. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a non-conducting core that comprises silicon dioxide (silica) and having a conducting shell layer comprising gold.26. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a non-conducting core that comprises silicon dioxide (silica) and having a conducting shell layer comprising silver.27. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter between 80-500 nm.28. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter between 100-200 nm.29. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter between 125-175 nm.30. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter between 150-170 nm.37ELUX-001-PCT31. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter between 80-500 nm; or between 100-200 nm; or between 125-175 nm; or between 150-170 nm; or about 125 nm; or about 150 nm; or about 160 nm; or about 170 nm; or about 175 nm; or about 200 nm.32. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter of about 125 nm.33. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter of about 150 nm.34. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter of about 160 nm.35. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter of about 170 nm.36. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter of about 175 nm.37. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a diameter of about 200 nm.38. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a conducting shell layer that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.39. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a conducting shell layer comprising gold that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.40. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells having a conducting shell layer comprising silver that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.38ELUX-001-PCT41. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 0.5 and 50 OD; the method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 1 and 25 OD; the method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 2.5 and 15 OD; the method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 2 and 10 OD; the method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 5 and 15 OD.42. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 0.5 and 50 OD; or between 0.25 and 50 OD; or about 0.5 and 25 OD; or between 1 and 10 OD; or between 1 and 3OD; or between 1 and 5 OD; or between 1 and 7.5 OD; or between 1 and 25 OD; or between 2.5 and 15 OD; or between 2 and 10 OD; or between 5 and 15 OD; or between 10 and 25 OD; or about 0.25 OD; or about 0.5 OD; or about 0.75 OD; or less than 2.5 OD; or less than 5 OD; or less than 7.5 OD; or less than 9 OD; or less than 10 OD.43. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 1 and 5 OD.44. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between between 1 and 7.5 OD45. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 1 and 3OD46. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 2 and 10 OD47. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 5 and 15 OD.48. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration between 10 and 25 OD.39ELUX-001-PCT49. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 0.5 OD.50. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 0.75 OD.51. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 1 OD.52. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 2 OD.53. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 2.5 OD.54. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 5 OD.55. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 7 OD.56. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 7.5 OD.57. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 8 OD.58. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 9 OD.59. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 10 OD.60. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 11 OD.61. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 12 OD.40ELUX-001-PCT62. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 12.5 OD.63. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 13 OD.64. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 14 OD.65. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 15 OD.66. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 16 OD.67. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 17 OD.68. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 18 OD.69. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 19 OD.70. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration of about 20 OD.71. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration less than between about 1x109particles per mL and 1x1012particles per mL.72. The method of any one of the previous embodiments, wherein said solution comprises said nanoparticles at a concentration less than 1.0 x1011particles per mL; or less than 7.5 x1010particles per mL; or less than 5 x1010particles per mL; or less than 1.0 x1010particles per mL; or less than 9.0 x109particles per mL; or less than 8.0 x109particles per mL; or between 1.0 x109and 1.0 x1011particles per mL; or between 2.0 x109and 5.0 x1010particles per mL; or between 2.0 x109and 1.0 x1010particles per mL; or between 3.0 x109and 8 x109particles per mL; or between 2.0 x109and 5 x109particles41ELUX-001-PCTper mL; or between 5 x109and 8 x109particles per mL; or about 3.0 x109particles per mL; or about 3.5 x109particles per mL; or about 5.0 x109particles per mL; or about 5.5 x109particles per mL; or about 6.0 x109particles per mL; or about 6.5 x109particles per mL; or about 7.0 x109particles per mL; or about 7.5 x109particles per mL; or about 8.0 x109particles per mL; or about 8.5 x109particles per mL; or about 9.0 x109particles per mL; or about 9.5 x109particles per mL; or about 1.0 x1010particles per mL; or about 1.5 x1010particles per mL; or about 2.0 x1010particles per mL; or about 2.5 x1010particles per mL; or about 5.0 x1010particles per mL; or about 7.5 x1010particles per mL.73. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 0.5 and 50 OD; or between 0.25 and 50 OD; or about 0.5 and 25 OD; or between 1 and 10 OD; or between 1 and 3OD; or between 1 and 5 OD; or between 1 and 7.5 OD; or between 1 and 25 OD; or between 2.5 and 15 OD; or between 2 and 10 OD; or between 5 and 15 OD; or between 10 and 25 OD; or about 0.25 OD; or about 0.5 OD; or about 0.75 OD; or less than 2.5 OD; or less than 5 OD; or less than 7.5 OD; or less than 9 OD; or less than 10 OD.74. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 1 and 5 OD.75. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between between 1 and 7.5 OD76. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 1 and 3OD77. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 2 and 10 OD42ELUX-001-PCT78. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 5 and 15 OD.79. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 0.5 and 50 OD.80. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 1 and 25 OD.81. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 2.5 and 15 OD.82. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 2 and 10 OD.83. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 5 and 15 OD.84. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 10 and 25 OD.85. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 1 OD.86. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 2 OD.43ELUX-001-PCT87. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 2.5 OD.88. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 5 OD.89. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 7 OD.90. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 7.5 OD.91. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 8 OD.92. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 9 OD.93. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 10 OD.94. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 11 OD.95. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 12 OD.44ELUX-001-PCT96. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 12.5 OD.97. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 13 OD.98. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 14 OD.99. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 15 OD.100. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 16 OD.101. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 17 OD.102. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 18 OD.103. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 19 OD.104. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 20 OD.45ELUX-001-PCT105. The method of any one of the previous embodiments, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration less than 1.0 E 11 particles per mL; or less than 7.5 E 10 particles per mL; or less than 5 E10 particles per mL.106. The method of any one of the previous embodiments, wherein said nanoparticles are gold nanoshells at a concentration less than between about 1x109particles per mL and 1x1012particles per mL.107. The method of any one of the previous embodiments, wherein said nanoparticles are gold nanoshells at a concentration less than 1.0 x1011particles per mL; or less than 7.5 x1010particles per mL; or less than 5 x1010particles per mL; or less than 1.0 x1010particles per mL; or less than 9.0 x109particles per mL; or less than 8.0 x109particles per mL; or between 1.0 x109and 1.0 x1011particles per mL; or between 2.0 x109and 5.0 x1010particles per mL; or between 2.0 x109and 1.0 x1010particles per mL; or between 3.0 x109and 8 x109particles per mL; or between 2.0 x109and 5 x109particles per mL; or between 5 x109and 8 x109particles per mL; or about 3.0 x109particles per mL; or about 3.5 x109particles per mL; or about 5.0 x109particles per mL; or about 5.5 x109particles per mL; or about 6.0 x109particles per mL; or about 6.5 x109particles per mL; or about 7.0 x109particles per mL; or about 7.5 x109particles per mL; or about 8.0 x109particles per mL; or about 8.5 x109particles per mL; or about 9.0 x109particles per mL; or about 9.5 x109particles per mL; or about 1.0 x1010particles per mL; or about 1.5 x1010particles per mL; or about 2.0 x1010particles per mL; or about 2.5 x1010particles per mL; or about 5.0 x1010particles per mL; or about 7.5 x1010particles per mL.108. The method of any one of the previous embodiments, wherein the photo-absorbing nanoparticles are administered in a tumescent solution wherein the volume of the tumescent solution is 100 – 5,000 mL; or 500 -3,000 mL; or 500-2,000 mL; or 500-1,500 mL; or 500-1,000 mL; or 1,000 – 2,000 mL; or 1,000 – 3,000 mL; or 1,000 – 5,000 mL; or about 500 mL; or about 1,000 mL; or about 1,500 mL; or about 2,000 mL; or about 2,500 mL; or about 3,000 mL; or about 4,000 mL; or about 5,000 mL.109. The method of any one of the preceding embodiments wherein the target fat is submental fat.46ELUX-001-PCT110. The method of any one of the previous embodiments, wherein wherein the photo-absorbing nanoparticles are administered in multiple injections and wherein about 0.2 mL; or 0.1-0.5 mL; or 0.15-0.25 mL; or about 0.15 mL; or about 0.175 mL; or about 0.19 mL; or about 0.21 mL; or about 0.22 mL; or about 0.23 mL; or about 0.24 mL; or about 0.25 mL; or about 0.3 mL; or about 0.5 mL of the photo-absorbing nanoparticles containing solution is delivered in each injection.111. The method of any one of the previous embodiments, wherein wherein the photo-absorbing nanoparticles are administered in multiple injections and wherein the method comprises administering about 20 total injections; or about 10-50 injections; or about 10-40 injections; or about 10-30 injections; or about 15-25 injections; or about 10 injections; or about 12 injections; or about 15 injections; or about 17 injections; or about 18 injections; or about 19 injections; or about 21 injections; or about 22 injections; or about 23 injections; or about 24 injections; or about 25 injections; or about 26 injections; or about 27 injections; or about 30 injections of the photo-absorbing nanoparticles containing solution.112. The method of any one of the previous embodiments, wherein wherein the photo-absorbing nanoparticles are administered in multiple injections and wherein each injection has a volume of 0.5- 20 mL; or 0.5-10 mL; or 0.5-5 mL; or 1-25 mL; or 1-20 mL; or 1-10 mL; or 1-5 mL; or 2-6 mL; or 2-10 mL; or 3-10 mL; or 5-10 mL; or 6-10 mL; or 7-10 mL; or 8-10 mL; or 2-8 mL; or 2-6 mL; or 3-5 mL; or about 1 mL; or about 2mL; or about 3 mL; or about 4 mL; or about 5 mL; or about 6 mL; or about 7 mL; or about 8 mL; or about 9 mL; or about 10 mL.113. The method of any one of the previous embodiments, wherein the nanoparticles are approximately spherical non-conducting core nanoshells.114. The method of any one of the previous embodiments, wherein the nanoparticles are approximately spherical non-conducting core nanoshells.115. The method of any one of the previous embodiments, wherein said nanoparticles are manufactured without the use of CTAB.116. The method of any one of the previous embodiments, wherein said nanoparticles are coated with PEG.47ELUX-001-PCT117. The method of any one of the previous embodiments, wherein the nanoparticles are nanoshells at a concentration between 1.0 x 109and 1.0 x 1011particles per mL, wherein the nanoshells comprise an overall diameter of between 150-170 nm, a gold outer shell of between 15 and 25 nm thickness that converts absorbed NIR light into heat via surface plasmon resonance, and a silicon dielectric core, and wherein cetyltrimethylammonium bromide (CTAB) is not used in the manufacture of the nanoshells.118. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at 1-60 J / cm2; or 1-20 J / cm2; or 5-15 J / cm2; or 5-10 J / cm2, or 10-15 J / cm2; or about 8 J / cm2; or about 9 J / cm2; or about 10 J / cm2; or about 11 J / cm2; or about 12 J / cm2; or about 13 J / cm2; or about 14 J / cm2; or about 15 J / cm2.119. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at 1-60 J / cm2.120. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at 1-20 J / cm2.121. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at 5-15 J / cm2.122. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at 5-10 J / cm2.123. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at 10-15 J / cm2.124. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at about 1 J / cm2; or about 2 J / cm2; or about 3 J / cm2; or about 4 J / cm2; or about 5 J / cm2; or about 6 J / cm2; or about 7 J / cm2; or about 8 J / cm2; or about 9 J / cm2; or about 10 J / cm2; or about 11 J / cm2; or about 12 J / cm2; or about 13 J / cm2; or about 14 J / cm2; or about 15 J / cm2.125. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at about 6 J / cm2.48ELUX-001-PCT126. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at about 12 J / cm2.127. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at a wavelength between 750 nm to 1100 nm.128. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at a wavelength of about 750 nm.129. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at a wavelength of about 800 nm.130. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at a wavelength of about 810 nm.131. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at a wavelength of about 1064 nm.132. The method of any one of the previous embodiments, wherein said pulses of near infrared light are administered at a frequency of 1-1000 Hz; 1-10 Hz, 10-100 Hz, 100-1000 Hz; or about 1 Hz; or about 2 Hz; or about 3 Hz; or about 4 Hz; or about 5 Hz; or about 6 Hz; or about 7 Hz; or about 8 Hz; or about 9 Hz; or about 10 Hz; or about 20 Hz; or about 25 Hz; or about 50 Hz; or about 100 Hz.133. The method of any one of the previous embodiments, wherein the method involves achieving a sustained temperature (or maximum sustained temperature) in the internal (local) treatment tissue / area of 40-75 °C; or 40-70 °C; or 40-65 °C; or 40-66 °C; or 40-55 °C; or 40-50 °C; or 40-45 °C; or 42-75 °C; 42-70 °C; or 42-65 °C; or 42-60 °C; or 42-55 °C; or 42-50 °C; or 45-75 °C; 45-70 °C; or 45-65 °C; or 45-60 °C; or 45-55 °C; or 45-50 °C; or 50-75 °C; 50-70 °C; or 50-65 °C; or 50-60 °C; or 50-55 °C; or 55-75 °C; 55-70 °C; or 55-65 °C; or 55-60 °C; or about 40 °C; or about 42 °C; or about 45 °C; or about 50 °C; or about 55 °C; or about 60 °C; or about 65 °C; or about 70 °C; or about 75 °C.134. The method of any one of the previous embodiments, wherein the method is performed such that the sustained local temperature (or maximum sustained local temperature) is below 85 °C; or below 80 °C; or below 75 °C; or below 70 °C; or below49ELUX-001-PCT69 °C; or below 68 °C; or below 65 °C; or below 64 °C; or below 63 °C; or below 62 °C; or below 61 °C; or below 60 °C; or below 59 °C; or below 58 °C; or below 57 °C; or below 56 °C; or below 55 °C; or below 54 °C; or 53 below °C; or below 52 °C; or below 51 °C; or below 50 °C throughout the procedure.135. The method of any one of the previous embodiments, wherein the method is performed such that the surface skin temperature is below 48 °C; or below 47 °C; or below 46 °C; or below 45 °C; or below 44 °C; or below 43 °C; or below 42 °C; or below 41 °C; or below 40 °C throughout the procedure.136. The method of any one of the previous embodiments, wherein said method further comprises aspirating a liquid from the target area, wherein the liquid comprises subcutaneous tissue and / or liquefied fat.137. The method of any one of the previous embodiments, wherein said method does not comprise aspirating liquid having subcutaneous tissue and / or liquefied fat from the target area after said injecting nanoparticles and said delivering near infrared light.138. A system for fat removal and / or skin tightening in accordance with any of the methods of the preceding embodiments, wherein the system comprises a solution of photo-absorbing nanoparticles as provided herein; a means for injecting the solution into the target area; and a near infrared light source for delivering a beam of light to the target area near infrared light source for delivering a beam of light to the target area.139. A system for fat removal and / or skin tightening in accordance with any of the methods of the preceding embodiments, wherein the system comprises a solution of photo-absorbing nanoparticles as provided herein; a means for injecting the solution into the target area; a near infrared light source for delivering a beam of light to the target area near infrared light source for delivering a beam of light to the target area; and a means for extracting melted fat from the target area.

[0068] The following examples are provided to further illustrate aspects and embodiments of the disclosure. These examples are non-limiting and should not be construed as limiting any aspects and embodiments of the disclosure.EXAMPLES50ELUX-001-PCT

[0069] Example 1: Comparison of Nanorods and Nanoshells

[0070] This experiment was designed to determine if 160nm spherical gold nanoshells could perform comparably to the 45nm x 15nm gold nanorods in fat reduction technology. Both materials were developed to resonate at a similar wavelength of 800nm. Properties of nanorods and nanoshells are shown on Table 1. The 160nm spherical gold nanoshells were acquired from NanoComposix, Product Number: GSGH800 (Gold Nanoshells, Peak Absorbance @800 nm, PEG, NanoXactTM). The nanoshells, but not the nanorods, used in these experiments were made without the use of CTAB. For these experiments, butter pads were sectioned and placed in petri dishes with a divot in the center of each pad to retain the devices full volume. The devices were distributed to their respectively labeled dishes, and exposed to the 800nm laser for an equivalent number of pulses. Based off the melting results of the butter, operators selected nanorods at 5 OD and nanoshells at 10 OD to be tested in porcine belly tissue due to the substantial fat release observed, however fat release was observed at all concentrations tested in the butter. After injecting the two devices in marked areas of the tissue in a grid pattern, dispensing approximately equal volumes in each area, the areas were exposed to the 800nm laser for an equivalent number of pulses. Overall, the new nanoshells were found to produce a similar, if not better effect in melting butter and comparable results with regard to porcine tissue softening.

[0071] MaterialsButter and Porcine Tissue (Pork Belly)Gold Nanoshells (32.3 OD, 1.04 mgAu / mL, 4.5 E 10 particles / mL); stored in 4CGold Nanorods (46.5 OD, 0.79 mgAu / mL, 7.8 E 12 particles / mL); stored in 4CSterile Water (Vehicle)15mL Eppendorf tubesP1000 and P200 Pipettes and tips3mL syringe with 23g injection needle51ELUX-001-PCT800nm Lasero Palomar Vectus Laser with 8.7cm2spot size was used for this test Vortex mixer

[0072] Table 1: Comparison of Exemplary Gold Nanorods and Gold Nanoshells.

[0073] ProceduresButter Test:Dilute the two different particles to the dilutions in Table 1 and 2 using sterile water.Power on the laser.o Laser used was the Palomar Vectus Laser52ELUX-001-PCTo Settings: Blonde (Hair color), High (Hair Density), Type I (Skin Type), Coarse (Hair diameter), 45ms pulse at 12 J / cm2Prepare and label petri dishes with pads of butter, making a small divot in the center of the butter deep enough to hold at least 200uL of test solution.Dispense 200uL of each test solution into the appropriately labeled divots in the butter.Deliver 40 consecutive pulses to each sample and record results.Porcine Tissue Test (Pig Belly):Select one concentration that showed good melting results in the butter for injection into the porcine tissue.Label a 2”x2” area with equally spaced injection sites to form a 7 x 7 grid. Mark an area of treatment with just the laser.Palpate the treatment regions to note the relative firmness before treatment.Using an injection needle and syringe, insert the needle in the marked grid, holding the syringe at such an angle that the test solutions are injected into the fat layer of the tissue.Depress the plunger slowly as the syringe is withdrawn to allow the space to fill with the test solutions, dispensing roughly 3mL between all injections (some volume leaked out).Repeat the previous two steps for the remaining marked injection sites.Wipe off the skin to remove any amount of solution that may have leaked out to ensure a clean treatment area.Deliver 40 consecutive pulses to the sample area and record the results.53ELUX-001-PCTo Settings: Blonde (Hair color), High (Hair Density), Type I (Skin Type), Coarse (Hair diameter), 45ms pulse at 12 J / cm2

[0074] Table 2: Nanorods

[0075] Table 3: Nanoshells

[0076] Results

[0077] The nanoshells and nanorods were diluted using sterile water from their stock concentrations of 32.3 OD and 46.5 OD, respectively, to the final concentrations for testing (see Table 1 and 2). Butter pads were placed into individually labeled petri dishes and a small indentation was pressed into the center. Each dilution was vortexed thoroughly to mix before 200uL of the test solutions were deposited on the respective butter pads, in the divots. The solution was dispensed slowly in order to ensure the full volume was retained in the divots. The laser was prepared at the following settings:Blonde (Hair color), High (Hair Density), Type I (Skin Type), Coarse (Hair diameter), 45ms pulse at 12 J / cm2. The butter with the various test solutions was exposed to 40 consecutive pulses while observed for melting. The laser head was held approximately ¾” from the sample and maintained in the same position during the laser treatment. The effective area of the laser was more than sufficient to cover the size of the treatment area. Melting was observed at all tested concentrations to varying degrees, with the vehicle only sample producing no visible melting (Figure 1).54ELUX-001-PCT

[0078] Based off the results of the butter melting, one concentration from each test device was selected for testing in the porcine tissue. The tissue was roughly 1” thick, with about a ¼” fat pad under the skin. The tissue was marked on the skin with a grid, and palpated to feel for firmness in the tissue. The operators elected to inject the rods at 5 OD, and the shells at 10 OD to ensure a robust response from both devices. Fourteen (14) injections were made in a 2”x2” region in a 7x7 grid on the porcine tissue (Figures 2 and 3), dispensing roughly 3mL of device in each region between the injections, with the operators wiping the area clean after all injections were performed. The two areas, as well as an untreated area were exposed to 40 pulses of the laser at the same settings as the butter. The 3 treated areas were then palpated after treatment and observations about tissue temperature and firmness were made. Both regions treated with the nanoparticles presented noticeable changes in the firmness of the tissue, with the changes not observed outside of the area injected. No palpable change was noted in the laser only treated region. Overall, there appeared to be a similar result in the porcine tissue between the 5 OD nanorods and the 10 OD nanoshells in the change of local firmness in the treated regions.

[0079] In these studies, the nanoshell device provided similar, if not better, results for the release of fat as the previously used nanorods. Based on various factors, it was expected to get equivalent fat melting with the nanoshells at 10 OD, compared to the rods at 2.5OD. We observed that, at 5 OD, significant melting was observed, and the shells appeared to work well at 2.5 OD. Further, we expected to get equivalent fat melting with the nanoshells at 1.40 x1010particles / mL, compared to the rods at 4.20x1011particles / mL. Instead, significant melting was observed at 6.98 x109nanoshells / mL, and the shells appeared to work well as low as at 3.48 x109Particles / mL. By providing an equivalent melting response to nanorods at less than 1% of the particle number and without a need to increase laser intensity, the present invention can provide better therapeutic control due to fewer heat-generating zones, which can result in less unnecessary temperature rise and more efficient temperature regulation within the tissue.

[0080] Example 2: Use of Nanoshells in a Human Liposuction

[0081] Patient Presentation:55ELUX-001-PCT

[0082] The patient presents with localized adiposity in the flanks and periumbilical region. The patient seeks aesthetic improvement in abdominal contour and reduction of redundant adipose tissue.

[0083] Procedure Performed:

[0084] Gold nanoshell and laser enhanced liposuction

[0085] Anesthesia:

[0086] General anesthesia with endotracheal intubation.

[0087] Position:

[0088] The patient is placed supine, with arms abducted at 90 degrees. The abdomen is prepped and draped in sterile fashion.

[0089] Tumescent Infiltration:

[0090] A total of 1,200 mL of tumescent solution is infiltrated into the subcutaneous tissue of the flanks, epigastric region, and lateral abdominal wall. The solution consists of lactated Ringer’s with lidocaine (0.05%), epinephrine (1:1,000,000), and gold nanoshells at a concentration of 2.5 OD, consistent with Example 1. Infiltration is performed using a blunt-tip 16-gauge multiport infiltration cannula, with even distribution and avoidance of intramuscular injection.

[0091] The outer skin of the treatment region is then exposed to 800 nm laser treatment (as in Example 1) for 2–8 passes to achieve controlled warming and fat melting. The laser is set to deliver 6 J / cm² in 30 ms pulses.

[0092] Liposuction Technique and Cannulas Used:

[0093] After adequate tumescence, vasoconstriction, and laser pretreatment, liposuction is performed with the following:

[0094] 3 mm Mercedes-tip cannula: used in the superficial and intermediate planes of the flanks, in a cross-tunneling pattern to achieve uniform contour.56ELUX-001-PCT

[0095] 4 mm basket cannula: used in the periumbilical and lower abdomen for bulk reduction, angled obliquely to prevent surface irregularities.

[0096] 2.5 mm microcannula: used in the epigastric transition zone for feathering and smooth contour blending.

[0097] The total aspirate volume is 1,450 mL, of which approximately 1,200 mL is adipose. The aspirate demonstrates a more liquefied consistency than typically observed without nanoshell and laser treatment. Blood loss is minimal.

[0098] Hemostasis and Closure:

[0099] Hemostasis is achieved with bipolar cautery as needed at cannula entry sites. Small access incisions are closed with interrupted 5-0 Monocryl.

[0100] Dressing and Postoperative Condition:

[0101] The incision sites are dressed with Steri-Strips and occlusive dressing. An abdominal binder is applied. The patient emerges from anesthesia without complication and is transferred to PACU in stable condition.

[0102] Example 3: Use of Nanoshells in a Human Fat Melting Without Liposuction

[0103] Patient Presentation:

[0104] The patient presents with localized adiposity in the flanks and periumbilical region. The patient seeks aesthetic improvement in abdominal contour and reduction of redundant adipose tissue.

[0105] Procedure Performed:

[0106] Gold nanoshell and laser enhanced liposuction

[0107] Anesthesia:

[0108] General anesthesia with endotracheal intubation.

[0109] Position:57ELUX-001-PCT

[0110] The patient is placed supine, with arms abducted at 90 degrees. The abdomen is prepped and draped in sterile fashion.

[0111] Tumescent Infiltration:

[0112] A total of 1,200 mL of tumescent solution is infiltrated into the subcutaneous tissue of the flanks, epigastric region, and lateral abdominal wall. The solution consists of lactated Ringer’s with lidocaine (0.05%), epinephrine (1:1,000,000), and gold nanoshells at a concentration of 2.5 OD, consistent with Example 1. Infiltration is performed using a blunt-tip 16-gauge multiport infiltration cannula, with even distribution and avoidance of intramuscular injection.

[0113] The outer skin of the treatment region is then exposed to 800 nm laser treatment (as in Example 1) for 2–8 passes to achieve controlled warming and fat melting. The laser is set to deliver 6 J / cm² in 30 ms pulses.

[0114] The procedure is completed without any liposuction or aspiration of adipose tissue. Over the next few days or weeks the fat in the treated area is reabsorbed naturally by the patient’s body.

[0115] Example 4: Use of Nanoshells in a Human Abdominoplasty with liposuction-assisted contouring

[0116] Patient Presentation:

[0117] A patient presents with significant lower abdominal skin laxity, rectus diastasis, and localized adiposity in the flanks and periumbilical region. seeks aesthetic improvement in contour and reduction of redundant tissue.

[0118] Procedure Performed:

[0119] Abdominoplasty with liposuction-assisted contouring enhanced by gold nanoshell and laser treatment.

[0120] Anesthesia:

[0121] General anesthesia with endotracheal intubation.

[0122] Position:58ELUX-001-PCT

[0123] The patient is placed supine, with arms abducted at 90 degrees. The abdomen is prepped and draped in sterile fashion.

[0124] Tumescent Infiltration:

[0125] A total of 1,200 mL of tumescent solution is infiltrated into the subcutaneous tissue of the flanks, epigastric region, and lateral abdominal wall. The solution consists of lactated Ringer’s with lidocaine (0.05%), epinephrine (1:1,000,000) and includes gold nanoshells at a concentration of 2.5 OD. The nanoshells are the same as used in Example 1. Infiltration is performed using a blunt-tip 16-gauge multiport infiltration cannula, with even distribution and avoidance of intramuscular injection.

[0126] The outer skin of the treatment region is then exposed to a 800nm laser treatment (as in Example 1) for 2-8 passes to achieve proper warming and fat melting. The laser is set to deliver 6 J / cm2in 30ms pulses.

[0127] Liposuction Technique and Cannulas Used:

[0128] After adequate tumescence and vasoconstriction, liposuction is performed with the following:

[0129] 3 mm Mercedes-tip cannula: used in the superficial and intermediate planes of the flanks, in a cross-tunneling pattern to achieve uniform contour.

[0130] 4 mm basket cannula: used in the periumbilical and lower abdomen for bulk reduction, angled obliquely to prevent surface irregularities.

[0131] 2.5 mm microcannula: used in the epigastric transition zone for feathering and smooth contour blending.

[0132] The total aspirate volume is 1,450 mL, of which approximately 1,200 mL is adipose, with minimal blood loss observed. Adipose tissue is in a more liquified status than usually experienced without nanoshell and laser treatment steps.

[0133] Excision and Rectus Plication:

[0134] A low transverse suprapubic incision is made and carried laterally to the anterior superior iliac spines. Dissection proceeds in the avascular plane to the level of the59ELUX-001-PCTumbilicus, which is circumscribed and preserved. Superior dissection continues to the costal margins. Rectus fascia is exposed, and a 4 cm diastasis is identified. A two-layer plication is performed with #1 looped PDS in a running fashion, reinforced with interrupted figure-of-eight sutures at sites of maximal tension.

[0135] Skin Resection and Umbilical Repositioning:

[0136] With advancement of the upper flap, excess infraumbilical tissue is resected, totaling 720 g. The umbilicus is delivered through a newly created aperture at the appropriate anatomical location and secured with interrupted 3-0 Monocryl sutures.

[0137] Hemostasis and Closure:

[0138] Hemostasis is achieved with bipolar cautery. Two 15-French Blake drains are placed through lateral stab incisions and secured. Closure is performed in three layers:

[0139] Scarpa’s fascia with interrupted 2-0 Vicryl.

[0140] Deep dermis with interrupted 3-0 Monocryl.

[0141] Subcuticular closure with running 4-0 Monocryl.

[0142] Dressing and Postoperative Condition:

[0143] The incision is dressed with Steri-Strips and occlusive dressing. An abdominal binder is applied. The patient emerges from anesthesia without complication and is transferred to PACU in stable condition.

[0144] Example 5: Use of Nanoshells in a Human Treatment for Improving the Appearance of Moderate to Severe Convexity or Fullness Associated with Submental Fat.

[0145] Patient Presentation:

[0146] The patient presents with moderate convexity and fullness of the submental region consistent with localized subcutaneous adiposity. The patient reports dissatisfaction with submental contour and seeks non-surgical improvement.

[0147] Procedure Performed:60ELUX-001-PCT

[0148] Subcutaneous injection of 160nm spherical gold nanoshells into the pre-platysmal submental fat.

[0149] Anesthesia:

[0150] Topical anesthetic cream (lidocaine / prilocaine 2.5% / 2.5%) is applied to the submental region for 30 minutes pre-procedure. An ice pack is applied immediately before injection for comfort and post-injection vasoconstriction.

[0151] Position:

[0152] The patient is placed in the supine position with the head slightly extended. The submental area is prepped with chlorhexidine solution and draped in sterile fashion.

[0153] Marking:

[0154] With the patient in upright position prior to prep, the borders of the treatment area are marked. The inferior border is delineated at the level of the thyroid cartilage, the superior border just inferior to the mandibular border, and lateral borders approximately 1.5–2 cm medial to the anterior border of the sternocleidomastoid muscles. The central submental convexity is identified for injection. A standard 1-cm injection grid is drawn using a sterile surgical marking pen.

[0155] Medication Preparation:

[0156] 160nm spherical gold nanoshells of Example 1 at a concentration of 2.5 OD in an appropriate saline solution are used. A total of 4 mL (20 mg / mL × 40 mg) is drawn for this session.

[0157] Instruments and Injection Technique:

[0158] Syringes: 1 mL Luer-Lock insulin syringes are prepared with 30-gauge, ½-inch needles.

[0159] Each injection site delivers 0.2 mL of solution.

[0160] Needles are introduced perpendicular to the skin at a depth of approximately 6 mm, ensuring deposition into the subcutaneous pre-platysmal fat layer. Care is taken to avoid intradermal, intramuscular, or peri-mandibular injection.61ELUX-001-PCT

[0161] Injections are distributed across a 1-cm grid, avoiding areas within 1–1.5 cm of the mandibular border to minimize risk to the marginal mandibular nerve.

[0162] Administration Pattern:

[0163] A total of 20 injections are administered in this session, corresponding to 4 mL total volume.

[0164] Each injection site is confirmed for absence of intravascular placement via negative aspiration.

[0165] The injection pattern evenly covers the central convex submental area, with slightly greater density of injections in the midline and tapering laterally.

[0166] Lazer Treatment

[0167] The outer skin of the treatment region is then exposed to 800 nm laser treatment (as in Example 1) for 2–8 passes to achieve controlled warming and fat melting. The laser is set to deliver 6 J / cm² in 30 ms pulses..

[0168] Immediate Post-Treatment Care:

[0169] Mild to moderate swelling is observed within minutes of injection, consistent with expected inflammatory response. No immediate complications are noted. The patient applies cold compresses intermittently for 15 minutes. The patient is advised regarding anticipated swelling, tenderness, numbness, and induration over the next 7–10 days.

[0170] Planned Subsequent Treatments:

[0171] The patient is scheduled for follow-up evaluation at 4 weeks. Depending on clinical response, subsequent sessions are planned at intervals of no less than 1 month, with a maximum of 6 total treatment sessions. Dose and grid coverage will be adjusted at each session based on reduction in submental convexity and distribution of residual fat.

[0172] Disposition:

[0173] The patient tolerates the procedure well and is discharged in stable condition with written aftercare instructions, including avoidance of strenuous activity and manipulation of the treated area for 24 hours. The patient is instructed to monitor for62ELUX-001-PCTsigns of difficulty swallowing, marginal mandibular nerve dysfunction, or severe pain and to report immediately if such occur.

[0001] It is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of embodiments in addition to those described and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein, as well as the abstract, are for the purpose of description and should not be regarded as limiting.

[0002] As such, those skilled in the art will appreciate that the conception upon which this disclosure is based may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.

[0003] While the invention has been described and exemplified in sufficient detail for those skilled in this art to make and use it, various alternatives, modifications, and improvements should be apparent without departing from the spirit and scope of the invention. The examples provided herein are representative of preferred embodiments, are exemplary, and are not intended as limitations on the scope of the invention.Modifications therein and other uses will occur to those skilled in the art. These modifications are encompassed within the spirit of the invention and are defined by the scope of the claims.

[0004] It will be readily apparent to a person skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention.

[0005] All patent applications, patents, publications and other references mentioned in the specification are indicative of the levels of those of ordinary skill in the art to which the invention pertains and are each incorporated herein by reference. The references cited herein are not admitted to be prior art to the claimed invention.63ELUX-001-PCT

[0006] Unless otherwise defined, all 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. In the case of conflict, the present specification, including definitions, will control.

[0007] The use of the articles “a”, “an”, and “the” in both the description and claims are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising”, “having”, “being of” as in “being of a chemical formula”, “including”, and “containing” are to be construed as open terms (i.e., meaning “including but not limited to”) unless otherwise noted.Additionally, whenever “comprising” or another open-ended term is used in an embodiment, it is to be understood that the same embodiment can be more narrowly claimed using the intermediate term “consisting essentially of” or the closed term “consisting of”.

[0008] The term “about”, “approximately”, or “approximate”, when used in connection with a numerical value, means that a collection or range of values is included. For example, “about X” includes a range of values that are ±20%, ±10%, ±5%, ±2%, ±1%, ±0.5%, ±0.2%, or ±0.1% of X, where X is a numerical value. In one embodiment, the term “about” refers to a range of values which are 10% more or less than the specified value. In another embodiment, the term “about” refers to a range of values which are 5% more or less than the specified value. In another embodiment, the term “about” refers to a range of values which are 1% more or less than the specified value. For the avoidance of doubt, the term about or approximately, when used in reference to a particular value contemplates and includes the particular specified value itself, for example the term “about 20” would specifically contemplate and include the value of exactly 20.

[0009] Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. A range used herein, unless otherwise specified, includes the two limits of the range. For example, the terms “between X and Y” and “range from X to Y, are inclusive of X and Y and the integers there between. On the other hand, when a series of individual values are referred to in the disclosure, any range64ELUX-001-PCTincluding any of the two individual values as the two end points is also conceived in this disclosure.

[0010] The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.

[0174] Other embodiments are set forth within the following claims.65

Claims

ELUX-001-PCTWhat is claimed is:

1. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area.

2. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise at least one non-conducting core layer and at least one conducting shell layer.

3. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have at least one axial dimension (diameter / length) longer that 100 nm.

4. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have an aspect ratio in the range of 1:1 to 1:2.

5. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles are substantially spherical.66ELUX-001-PCT6. A method for fat removal and / or skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles into adipose tissue in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise a core and a shell encapsulating the core, wherein said shell comprises at least one atomic element not included in the core.

7. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area.

8. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise at least one non-conducting core layer and at least one conducting shell layer.

9. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have at least one axial dimension (diameter / length) longer that 100 nm.

10. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles have an aspect ratio in the range of 1:1 to 1:2.

11. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles are substantially spherical.67ELUX-001-PCT12. A method for skin tightening in a subject, said method comprising injecting a solution comprising a plurality of photo-absorbing nanoparticles subdermally in a target area of said subject and delivering a series of pulses of near infrared light across an area of skin overlying the target area; wherein said nanoparticles comprise a core and a shell encapsulating the core, wherein said shell comprises at least one atomic element not included in the core.

13. The method of any one of the previous claims, wherein the nanoparticles have an aspect ratio of about 1:1.

14. The method of any one of the previous claims, wherein the nanoparticles are nanoshells.

15. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a non-conducting core that comprises dielectric materials and / or semiconductor materials.

16. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a non-conducting core that comprises one or more dielectric materials selected from the group consisting of silicon dioxide (silica), titanium dioxide, polymethyl methacrylate (PMMA), polystyrene, gold sulfide and macromolecules such as dendrimers.

17. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a non-conducting core that comprises silicon dioxide (silica).

18. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a conducting shell layer comprising one or more metals selected from the group consisting of gold, silver, copper, platinum, palladium, lead, and iron.

19. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a conducting shell layer comprising one or more metals selected from the group consisting of gold and silver.

20. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a conducting shell layer comprising gold.68ELUX-001-PCT21. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a conducting shell layer comprising silver.

22. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a non-conducting core that comprises one or more dielectric materials selected from the group consisting of silicon dioxide (silica), titanium dioxide, polymethyl methacrylate (PMMA), polystyrene, gold sulfide and macromolecules such as dendrimers; and having a conducting shell layer having23. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a non-conducting core that comprises one or more dielectric materials selected from the group consisting of silicon dioxide (silica), titanium dioxide, polymethyl methacrylate (PMMA), polystyrene, gold sulfide and macromolecules such as dendrimers; and having a conducting shell layer comprising one or more metals selected from the group consisting of gold, silver, copper, platinum, palladium, lead, and iron.

24. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a non-conducting core that comprises silicon dioxide (silica) and having a conducting shell layer comprising one or more metals selected from the group consisting of gold and silver.

25. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a non-conducting core that comprises silicon dioxide (silica) and having a conducting shell layer comprising gold.

26. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a non-conducting core that comprises silicon dioxide (silica) and having a conducting shell layer comprising silver.

27. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter between 80-500 nm.

28. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter between 100-200 nm.

29. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter between 125-175 nm.69ELUX-001-PCT30. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter between 150-170 nm.

31. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter between 80-500 nm; or between 100-200 nm; or between 125-175 nm; or between 150-170 nm; or about 125 nm; or about 150 nm; or about 160 nm; or about 170 nm; or about 175 nm; or about 200 nm.

32. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter of about 125 nm.

33. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter of about 150 nm.

34. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter of about 160 nm.

35. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter of about 170 nm.

36. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter of about 175 nm.

37. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a diameter of about 200 nm.

38. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a conducting shell layer that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.

39. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a conducting shell layer comprising gold that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.70ELUX-001-PCT40. The method of any one of the previous claims, wherein the nanoparticles are nanoshells having a conducting shell layer comprising silver that is between 5 and 50 nm thick; or between 10 and 30 nm thick; or between 15 and 25 nm thick; or about 15 nm thick; or about 20 nm thick; or about 25 nm thick.

41. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 0.5 and 50 OD; the method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 1 and 25 OD; the method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 2.5 and 15 OD; the method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 2 and 10 OD; the method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 5 and 15 OD.

42. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 0.5 and 50 OD; or between 0.25 and 50 OD; or about 0.5 and 25 OD; or between 1 and 10 OD; or between 1 and 3OD; or between 1 and 5 OD; or between 1 and 7.5 OD; or between 1 and 25 OD; or between 2.5 and 15 OD; or between 2 and 10 OD; or between 5 and 15 OD; or between 10 and 25 OD; or about 0.25 OD; or about 0.5 OD; or about 0.75 OD; or less than 2.5 OD; or less than 5 OD; or less than 7.5 OD; or less than 9 OD; or less than 10 OD.

43. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 1 and 5 OD.

44. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between between 1 and 7.5 OD45. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 1 and 3OD46. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 2 and 10 OD71ELUX-001-PCT47. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 5 and 15 OD.

48. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration between 10 and 25 OD.

49. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 0.5 OD.

50. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 0.75 OD.

51. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 1 OD.

52. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 2 OD.

53. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 2.5 OD.

54. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 5 OD.

55. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 7 OD.

56. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 7.5 OD.

57. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 8 OD.

58. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 9 OD.

59. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 10 OD.72ELUX-001-PCT60. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 11 OD.

61. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 12 OD.

62. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 12.5 OD.

63. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 13 OD.

64. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 14 OD.

65. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 15 OD.

66. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 16 OD.

67. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 17 OD.

68. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 18 OD.

69. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 19 OD.

70. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration of about 20 OD.

71. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration less than between about 1x109particles per mL and 1x1012particles per mL.73ELUX-001-PCT72. The method of any one of the previous claims, wherein said solution comprises said nanoparticles at a concentration less than 1.0 x1011particles per mL; or less than 7.5 x1010particles per mL; or less than 5 x1010particles per mL; or less than 1.0 x1010particles per mL; or less than 9.0 x109particles per mL; or less than 8.0 x109particles per mL; or between 1.0 x109and 1.0 x1011particles per mL; or between 2.0 x109and 5.0 x1010particles per mL; or between 2.0 x109and 1.0 x1010particles per mL; or between 3.0 x109and 8 x109particles per mL; or between 2.0 x109and 5 x109particles per mL; or between 5 x109and 8 x109particles per mL; or about 3.0 x109particles per mL; or about 3.5 x109particles per mL; or about 5.0 x109particles per mL; or about 5.5 x109particles per mL; or about 6.0 x109particles per mL; or about 6.5 x109particles per mL; or about 7.0 x109particles per mL; or about 7.5 x109particles per mL; or about 8.0 x109particles per mL; or about 8.5 x109particles per mL; or about 9.0 x109particles per mL; or about 9.5 x109particles per mL; or about 1.0 x1010particles per mL; or about 1.5 x1010particles per mL; or about 2.0 x1010particles per mL; or about 2.5 x1010particles per mL; or about 5.0 x1010particles per mL; or about 7.5 x1010particles per mL.

73. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 0.5 and 50 OD; or between 0.25 and 50 OD; or about 0.5 and 25 OD; or between 1 and 10 OD; or between 1 and 3OD; or between 1 and 5 OD; or between 1 and 7.5 OD; or between 1 and 25 OD; or between 2.5 and 15 OD; or between 2 and 10 OD; or between 5 and 15 OD; or between 10 and 25 OD; or about 0.25 OD; or about 0.5 OD; or about 0.75 OD; or less than 2.5 OD; or less than 5 OD; or less than 7.5 OD; or less than 9 OD; or less than 10 OD.

74. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 1 and 5 OD.

75. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between between 1 and 7.5 OD74ELUX-001-PCT76. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 1 and 3OD77. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 2 and 10 OD78. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 5 and 15 OD.

79. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 0.5 and 50 OD.

80. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 1 and 25 OD.

81. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 2.5 and 15 OD.

82. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 2 and 10 OD.

83. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 5 and 15 OD.

84. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration between 10 and 25 OD.75ELUX-001-PCT85. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 1 OD.

86. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 2 OD.

87. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 2.5 OD.

88. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 5 OD.

89. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 7 OD.

90. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 7.5 OD.

91. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 8 OD.

92. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 9 OD.

93. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 10 OD.

94. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 11 OD.

95. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 12 OD.

96. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 12.5 OD.76ELUX-001-PCT97. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 13 OD.

98. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 14 OD.

99. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 15 OD.

100. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 16 OD.

101. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 17 OD.

102. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 18 OD.

103. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 19 OD.

104. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration of about 20 OD.

105. The method of any one of the previous claims, wherein said nanoparticles are nanoshells and said solution comprises said nanoshells at a concentration less than 1.0 E 11 particles per mL; or less than 7.5 E 10 particles per mL; or less than 5 E10 particles per mL.

106. The method of any one of the previous claims, wherein said nanoparticles are gold nanoshells at a concentration less than between about 1x109particles per mL and 1x1012particles per mL.77ELUX-001-PCT107. The method of any one of the previous claims, wherein said nanoparticles are gold nanoshells at a concentration less than 1.0 x1011particles per mL; or less than 7.5 x1010particles per mL; or less than 5 x1010particles per mL; or less than 1.0 x1010particles per mL; or less than 9.0 x109particles per mL; or less than 8.0 x109particles per mL; or between 1.0 x109and 1.0 x1011particles per mL; or between 2.0 x109and 5.0 x1010particles per mL; or between 2.0 x109and 1.0 x1010particles per mL; or between 3.0 x109and 8 x109particles per mL; or between 2.0 x109and 5 x109particles per mL; or between 5 x109and 8 x109particles per mL; or about 3.0 x109particles per mL; or about 3.5 x109particles per mL; or about 5.0 x109particles per mL; or about 5.5 x109particles per mL; or about 6.0 x109particles per mL; or about 6.5 x109particles per mL; or about 7.0 x109particles per mL; or about 7.5 x109particles per mL; or about 8.0 x109particles per mL; or about 8.5 x109particles per mL; or about 9.0 x109particles per mL; or about 9.5 x109particles per mL; or about 1.0 x1010particles per mL; or about 1.5 x1010particles per mL; or about 2.0 x1010particles per mL; or about 2.5 x1010particles per mL; or about 5.0 x1010particles per mL; or about 7.5 x1010particles per mL.

108. The method of any one of the previous claims, wherein the photo-absorbing nanoparticles are administered in a tumescent solution wherein the volume of the tumescent solution is 100 – 5,000 mL; or 500 -3,000 mL; or 500-2,000 mL; or 500-1,500 mL; or 500-1,000 mL; or 1,000 – 2,000 mL; or 1,000 – 3,000 mL; or 1,000 – 5,000 mL; or about 500 mL; or about 1,000 mL; or about 1,500 mL; or about 2,000 mL; or about 2,500 mL; or about 3,000 mL; or about 4,000 mL; or about 5,000 mL.

109. The method of any one of the preceding claims wherein the target fat is submental fat.

110. The method of any one of the previous claims, wherein wherein the photo-absorbing nanoparticles are administered in multiple injections and wherein about 0.2 mL; or 0.1-0.5 mL; or 0.15-0.25 mL; or about 0.15 mL; or about 0.175 mL; or about 0.19 mL; or about 0.21 mL; or about 0.22 mL; or about 0.23 mL; or about 0.24 mL; or about 0.25 mL; or about 0.3 mL; or about 0.5 mL of the photo-absorbing nanoparticles containing solution is delivered in each injection.78ELUX-001-PCT111. The method of any one of the previous claims, wherein wherein the photo-absorbing nanoparticles are administered in multiple injections and wherein the method comprises administering about 20 total injections; or about 10-50 injections; or about 10-40 injections; or about 10-30 injections; or about 15-25 injections; or about 10 injections; or about 12 injections; or about 15 injections; or about 17 injections; or about 18 injections; or about 19 injections; or about 21 injections; or about 22 injections; or about 23 injections; or about 24 injections; or about 25 injections; or about 26 injections; or about 27 injections; or about 30 injections of the photo-absorbing nanoparticles containing solution.

112. The method of any one of the previous claims, wherein wherein the photo-absorbing nanoparticles are administered in multiple injections and wherein each injection has a volume of 0.5- 20 mL; or 0.5-10 mL; or 0.5-5 mL; or 1-25 mL; or 1-20 mL; or 1-10 mL; or 1-5 mL; or 2-6 mL; or 2-10 mL; or 3-10 mL; or 5-10 mL; or 6-10 mL; or 7-10 mL; or 8-10 mL; or 2-8 mL; or 2-6 mL; or 3-5 mL; or about 1 mL; or about 2mL; or about 3 mL; or about 4 mL; or about 5 mL; or about 6 mL; or about 7 mL; or about 8 mL; or about 9 mL; or about 10 mL.

113. The method of any one of the previous claims, wherein the nanoparticles are approximately spherical non-conducting core nanoshells.

114. The method of any one of the previous claims, wherein the nanoparticles are approximately spherical non-conducting core nanoshells.

115. The method of any one of the previous claims, wherein said nanoparticles are manufactured without the use of CTAB.

116. The method of any one of the previous claims, wherein said nanoparticles are coated with PEG.

117. The method of any one of the previous claims, wherein the nanoparticles are nanoshells at a concentration between 1.0 x 109and 1.0 x 1011particles per mL, wherein the nanoshells comprise an overall diameter of between 150-170 nm, a gold outer shell of between 15 and 25 nm thickness that converts absorbed NIR light into heat via surface plasmon resonance, and a silicon dielectric core, and wherein cetyltrimethylammonium bromide (CTAB) is not used in the manufacture of the nanoshells.79ELUX-001-PCT118. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at 1-60 J / cm2; or 1-20 J / cm2; or 5-15 J / cm2; or 5-10 J / cm2, or 10-15 J / cm2; or about 8 J / cm2; or about 9 J / cm2; or about 10 J / cm2; or about 11 J / cm2; or about 12 J / cm2; or about 13 J / cm2; or about 14 J / cm2; or about 15 J / cm2.

119. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at 1-60 J / cm2.

120. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at 1-20 J / cm2.

121. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at 5-15 J / cm2.

122. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at 5-10 J / cm2.

123. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at 10-15 J / cm2.

124. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at about 1 J / cm2; or about 2 J / cm2; or about 3 J / cm2; or about 4 J / cm2; or about 5 J / cm2; or about 6 J / cm2; or about 7 J / cm2; or about 8 J / cm2; or about 9 J / cm2; or about 10 J / cm2; or about 11 J / cm2; or about 12 J / cm2; or about 13 J / cm2; or about 14 J / cm2; or about 15 J / cm2.

125. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at about 6 J / cm2.

126. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at about 12 J / cm2.

127. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at a wavelength between 750 nm to 1100 nm.

128. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at a wavelength of about 750 nm.80ELUX-001-PCT129. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at a wavelength of about 800 nm.

130. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at a wavelength of about 810 nm.

131. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at a wavelength of about 1064 nm.

132. The method of any one of the previous claims, wherein said pulses of near infrared light are administered at a frequency of 1-1000 Hz; 1-10 Hz, 10-100 Hz, 100-1000 Hz; or about 1 Hz; or about 2 Hz; or about 3 Hz; or about 4 Hz; or about 5 Hz; or about 6 Hz; or about 7 Hz; or about 8 Hz; or about 9 Hz; or about 10 Hz; or about 20 Hz; or about 25 Hz; or about 50 Hz; or about 100 Hz.

133. The method of any one of the previous claims, wherein the method involves achieving a sustained temperature (or maximum sustained temperature) in the internal (local) treatment tissue / area of 40-75 °C; or 40-70 °C; or 40-65 °C; or 40-66 °C; or 40-55 °C; or 40-50 °C; or 40-45 °C; or 42-75 °C; 42-70 °C; or 42-65 °C; or 42-60 °C; or 42-55 °C; or 42-50 °C; or 45-75 °C; 45-70 °C; or 45-65 °C; or 45-60 °C; or 45-55 °C; or 45-50 °C; or 50-75 °C; 50-70 °C; or 50-65 °C; or 50-60 °C; or 50-55 °C; or 55-75 °C; 55-70 °C; or 55-65 °C; or 55-60 °C; or about 40 °C; or about 42 °C; or about 45 °C; or about 50 °C; or about 55 °C; or about 60 °C; or about 65 °C; or about 70 °C; or about 75 °C.

134. The method of any one of the previous claims, wherein the method is performed such that the sustained local temperature (or maximum sustained local temperature) is below 85 °C; or below 80 °C; or below 75 °C; or below 70 °C; or below 69 °C; or below 68 °C; or below 65 °C; or below 64 °C; or below 63 °C; or below 62 °C; or below 61 °C; or below 60 °C; or below 59 °C; or below 58 °C; or below 57 °C; or below 56 °C; or below 55 °C; or below 54 °C; or 53 below °C; or below 52 °C; or below 51 °C; or below 50 °C throughout the procedure.81ELUX-001-PCT135. The method of any one of the previous claims, wherein the method is performed such that the surface skin temperature is below 48 °C; or below 47 °C; or below 46 °C; or below 45 °C; or below 44 °C; or below 43 °C; or below 42 °C; or below 41 °C; or below 40 °C throughout the procedure.

136. The method of any one of the previous claims, wherein said method further comprises aspirating a liquid from the target area, wherein the liquid comprises subcutaneous tissue and / or liquefied fat.

137. The method of any one of the previous claims, wherein said method does not comprise aspirating liquid having subcutaneous tissue and / or liquefied fat from the target area after said injecting nanoparticles and said delivering near infrared light.

138. A system for fat removal and / or skin tightening in accordance with any of the methods of the preceding claims, wherein the system comprises a solution of photo-absorbing nanoparticles as provided herein; a means for injecting the solution into the target area; and a near infrared light source for delivering a beam of light to the target area near infrared light source for delivering a beam of light to the target area.

139. A system for fat removal and / or skin tightening in accordance with any of the methods of the preceding claims, wherein the system comprises a solution of photo-absorbing nanoparticles as provided herein; a means for injecting the solution into the target area; a near infrared light source for delivering a beam of light to the target area near infrared light source for delivering a beam of light to the target area; and a means for extracting melted fat from the target area.82

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