Silver nanoplate compositions and methods

Description of the invention

PARTIES OF THE CONTRACT ON JOINT WORK

RESEARCH

[0001] The invention described herein was developed pursuant to a collaborative research agreement between Sienna Labs, Inc. and nanoComposix, Inc.

BACKGROUND OF THE INVENTION

Field of the Invention

The invention relates to a method for the preparation of high optical density solutions of silver nanoparticles (e.g. nanoparticles) as well as solutions and substrates prepared by said method.

Description of the state of the art

[0003] Nanoparticles, including nanospheres, nanorods, nanowires, nanowires, nanoplates, and particles of other shapes, can be synthesized from a variety of materials. In one embodiment, the lamellar nanoparticle is a nanoplate. Nanoparticles made of metals such as gold and silver have unique optical properties that can be tuned to interact with light across the electromagnetic spectrum based on surface plasmon resonance assisted by these nanomaterials. Technologies that take advantage of the unique optical properties of silver nanoparticles include, but are not limited to, diagnostic technologies, photonics, medical technologies, and masking. High optical density nanoparticle solutions may be used in a subset of these technologies, including but not limited to photothermal ablation of tumors, hair removal, acne treatment, wound healing, and antibacterial applications. Silver nanoparticles, also known as silver lamellar nanoparticles or nanoprisms, are of particular interest to technologies that use the optical properties of nanoparticles due to their tunable spectral peaks and very high optical yields. Although methods for producing silver nanoplatelets by photoconversion technique have been developed (Jin et al. 2001; Jin et al.

and

EP 2 906 286 Β1

2003), photoconversion under pH control (Xue 2007), thermal growth (Hao et al. 2004; Hao 2002; He 2008; Metraux 2005), growth on a template (Hao et al. 2004; Hao 2002) and seed-mediated growth ( Aherne 2008; Chen; Carroll 2003; Chen; Carroll 2002, 2004; Chen et al. 2002; He 2008; Le Guevel 2009; Xiong et al. 2007), these methods provide relatively dilute solutions with a suitably low optical density in the range visible and near-infrared light.

SUMMARY

[0004] For many applications of silver nanoplatelets, more concentrated solutions of silver nanoplatelets are needed and especially preferred. In some cases, where the prepared silver platelet solutions are concentrated to obtain a higher optical density by previously developed methods, the shape of the nanoparticles may change, thereby changing optical properties such as optical density. In many cases, these changes result in an undesirable degradation of the optical properties of the nanoparticles. Accordingly, several embodiments of the present invention provide methods for preparing silver nanoplate solutions with higher concentrations and increased optical density while reducing the degradation of the optical properties of the silver nanoplatelets. In various embodiments, the methods of the present invention enable the preparation of dilute silver nanoplatelet solutions, high optical density silver nanoplate solutions and partially, substantially or fully retaining the shape and optical properties of the prepared silver nanoplatelets upon increasing particle concentration.

[0005] Various embodiments of the invention provide methods for the preparation of high optical density silver nanoparticle solutions, and nanoparticles and solutions prepared by these methods. In one embodiment, the process comprises replacing one or more original ingredients (e.g., chemical or biological agents) bound or otherwise associated with the surface of the nanoparticles with a stabilizer. In another embodiment, the stabilizer not so much replaces the original component as complements or modifies the original component.

EP 2 906 286 Β1

The stabilizer can be a biological or chemical substance that stabilizes the nanoplates before, during and / or after concentration, and thus allows for obtaining a stable solution of silver nanoplates with high optical density. The process also involves increasing the concentration of silver nanoparticles in the solution, thereby increasing the optical density of the solution. In several embodiments, the high optical density stability of the solution (i.e. the properties of the particles in solution such as shape, size, optical properties, response maximum, plasmonic properties, etc., remain unchanged or substantially unchanged during the process described. Several embodiments of the present invention contain a solution of high optical density silver nanoplates stabilized with stabilizers (i.e. particles, chemicals and / or biological agents bound to the surface of the nanoparticles). In one embodiment, the invention comprises a solution of silver nanoplatelets surface functionalized with chemical or biological agents deposited on the surface by physical adsorption, molecularly bound to the surface based on specific interactions, or surrounding each of the nanoparticles.

[0006] In one embodiment, a high optical density silver nanoplate solution is bonded to a substrate. In one embodiment, a portion of the nanoparticles in the solution binds to the substrate to form a nanoplate-substrate composite. Silver nanoplatelet solutions with high optical density can be applied to substrates to form nanoplatelet composites in which a significant portion of the substrate surface area is coated with nanoplates. In the present invention, the substrate comprises fibers.

[0007] In some embodiments, the process of increasing the optical density of a stable solution of silver nanoplatelets comprises (i) preparing a solution comprising a plurality of plate-shaped nanoplates; (ii) adding a stabilizer to the solution, wherein the stabilizer comprises a polyvinyl-based polymer and borate; and (iii) concentrating the solution to obtain a concentrated solution, wherein the concentrated solution comprises a plurality of plate-shaped nanoplates and wherein said concentrated solution has a maximum optical density of

ΕΡ 2 906 286 Β1 over 10 cm '¹.

[0008] There is also described a method of making a stable, high optical density silver nanoplatelet solution comprising: (i) adding a stabilizer to the silver nanoplate solution; (ii) adding a buffer (e.g. a water-soluble salt buffer) for the silver nanoplatelet solution; (iii) mixing the stabilizer, the buffer and the silver nanoplatelet for a time sufficient for the stabilizer to react with the water-soluble salt in the buffer on the surface of the silver nanoplate; and (iv) concentrating the solution to a maximum optical density greater than 10 cm^-1 (e.g. 50-1500 cm^-1).

[0009] The stabilizers include a polyvinyl-based polymer (e.g., polyvinyl alcohol (PVA) and / or poly (vinylpyrrolidone (PVP)) and borate, and may further include one or more of the following components: sodium citrate, water soluble polymer (e.g. sodium polystyrene sulfonate and / or sulfone derivative of hydrocarbon polymer), polyethylene glycol, poly (acrylic acid), dextran, water soluble salt including one or more salts from the group consisting of sulfates, carbonates, chromates , phosphates and sulphites, acetates and nitrates. In various embodiments, the addition or combination of a stabilizer stabilizes the nanoplate formulation, and one of the salt components may interact with the stabilizer to result in stabilizer cross-linking and increasing the durability of the silver nanoplate coating. In one embodiment, the starting solution of silver nanoplatelets may be obtained from a solution comprising one or more stabilizers and a source of silver (e.g. silver salt or elemental silver seeds) using chemicals, biologicals, agitation, electromagnetic radiation and / or heat to reduce the silver source (e.g. photoconversion, pH controlled photoconversion, thermal growth, stencil growth and / or seed-mediated methods) growth).

[0010] In various embodiments, the process of concentrating a silver nanoplate solution comprises the steps of preparing a solution comprising a plurality of silver nanoplates having a maximum optical density less than 10 cm.^-1 (e.g. 0.1 - 9.9 cm^-1, 1-9 cm^-1, 3-7 cm^-1, 1-5 cm^-1 and / or 5-10 cm^-1), adding to

ΕΡ 2 906 286 Β1 stabilizer solution and concentrating the solution to a maximum optical density above 10 cm^-1 (e.g. 80-150 cm^-1, 900-1100 cm^-1, 100 cm^-1, 1000 cm^-1 or more). In various embodiments, the maximum optical density is increased by 10%, 50%, 100%, 200%, 500%, 1000%, 10,000% or more and / or increased by a ratio of 1: 1.5, 1: 2, 1. : 5, 1:10 or greater and / or an increase with a multiplicity factor of 1, 1.5, 2, 5, 10, 25, 50, 100, 1000 or more.

[0011] In various embodiments, the silver nanoplates have a size ratio of between 1.5 and 50 (e.g., 1.5-10, 25-50). In one embodiment, the silver nanoplates have an edge length between 10 nm to 300 nm (e.g., 50-250, 65-100 nm). In various embodiments, the stabilizer is further sodium citrate or at least one water-soluble polymer selected from the group consisting of sodium polystyrene sulfonate and a sulfone derivative of a hydrocarbon polymer. In some embodiments , the water-soluble salt further comprises one or more salts from the group consisting of sulfates, carbonates, chromates, phosphates, and sulfites, acetates, and nitrates. In one embodiment, the stabilizer further comprises at least one compound from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, polyacrylic acid, and dextran. In one embodiment, the stabilizer further comprises a thiol-containing molecule. The thiol-containing molecule can be dihydrolipoic acid or a derivative thereof. The process optionally includes the steps of isolating the concentrated nanoparticles and encasing the isolated concentrated nanoparticles with a coating (e.g., silica or other material). The described process includes the step of concentrating the sheathed nanoplates to an optical density above 10 cm^-1 (e.g. 100 cm^-1, 1000 cm^-1 or higher). The stabilizer is added prior to the preparation of the silver nanoplatelets. In one embodiment, the nanoplates are concentrated by tangential filtration. In one embodiment, the concentration of silver is greater than 1.0 mg / ml (e.g. 1-1000, 10-300 mg / ml).

[0012] In various embodiments, a process for making metal oxide coated silver nanoplatelets is provided. Such a process may include

ΕΡ 2 906 286 Β1 stages of providing a solution of silver nanoplatelets with the maximum absorption in the range from 500 to 1500 nm (e.g. 600-1400, 800-1200 nm) and optical density above 10 cm^-1 (e.g. 100 cm^-1, 1000 cm^-1 or more) and combining this solution with a solution of a metal oxide or metal oxide precursor in an amount sufficient to form a metal oxide coating on the outer surface of the silver nanoplates. In some embodiments, silver nanoplates are bonded to a stabilizing polymer (e.g. poly (vinylpyrrolidone, polyvinyl alcohol) or a combination thereof, for example by applying a stabilizing polymer to the outer surface of the silver nanoplatelets. In various embodiments, the metal oxide is silica or the metal oxide comprises silica.

[0013] In various embodiments, the process of making a silver nanoplatelet solution comprises the steps of providing a solution containing a reducer, a stabilizer, a water-soluble polymer, and a silver salt, producing a plurality of silver nuclei from the solution, causing the plurality of nuclei to grow, leading to the formation of multiple nanoplates in the solution, silver nanoplatelet solution, adding a stabilizer to the silver nanoplatelet solution, adding a buffer containing water-soluble salt to the silver nanoplatelet solution and concentrating the silver nanoplate solution to a maximum optical density above 10 cm^-1 (e.g. 100 cm^-1, 1000 cm^-1 or more).

[0014] In various embodiments, the composition comprises or consists essentially of a solution of silver nanoplatelets, which silver nanoplates include a polyvinyl polymer. In some embodiments, the polyvinyl polymer is poly (vinylpyrrolidone) or poly (vinyl alcohol). The composition (e.g., solution) comprises borates and optionally one or more salts (e.g., sulfates, carbonates, chromates, phosphates, and sulfites, acetates, and nitrites).

[0015] In various embodiments, the polyvinyl polymer is bonded to the salt, the polyvinyl polymer coats at least a portion of the surface of the silver nanoplatelet, and / or the polyvinyl polymer is applied to the outer surface of the silver nanoplate. In one embodiment, the solution comprises

EP 2 906 286 Β1 silver nanoslabs in a concentration that allows the non-metallic coating material present in the solution to adhere to them. The solution can be made up as concentrated. In some embodiments, the optical density of the silver solution or nanoplates is greater than 10 cm^-1 (e.g. 100 cm^-1, 1000 cm^-1 or more). The solution may contain borate and, optionally, another salt (sulfates, carbonates, chromates, phosphates, and sulfites, acetates, and nitrites) at a concentration greater than 0.1 mM (e.g., from 0.1 mM to 10 mM). In one embodiment, the solution has a pH greater than 7 (e.g., in the range 8-13). In some embodiments, the absorption spectrum of the silver nanoplatelet comprises a maximum at a wavelength between 500 and 1500 nm (e.g., 6001400, 550-1100, 810-830, 1000-1100 nm). In one embodiment, the solution additionally comprises bicarbonate. The silver nanoplates can be coated with silica. Silver nanoplates can have edges between 10 nm and 500 nm (e.g. 50-300, 100-150 nm).

[0016] In various embodiments, the composition comprises or consists essentially of a solution of silver nanoplatelets bonded to a coating material comprising a polyvinyl polymer. In one embodiment, the silver nanoplates are substantially coated with a polyvinyl polymer. In various embodiments, the composition comprises a metal oxide, the metal oxide comprises silicon, the polyvinyl polymer comprises polyvinyl alcohol or polyvinylpyrrolidone, silver nanoplates are bonded to polyvinyl alcohol and silica, and / or silver nanoplates are bonded to poly (vinyl) alcohol. vinylpyrrolidone and silica or any combination thereof In one embodiment, the composition comprises a moiety selected from the group consisting of an amino group and a mercaptyl group. In one embodiment, the remainder is related to silica. In one embodiment, the optical density of the solution is greater than 10 cm^-1 (e.g. 1-1100 cm^-1 or more). In one embodiment, the density of the silver nanoplates is greater than 10 cm^-1 (e.g. 100 cm^-1, 1000 cm^-1, 11-5000 cm^-1 or more). In some embodiments, the solution comprises borate and optionally another water-soluble salt (e.g., sulfates, carbonates, chromates, phosphates, and sulfites, acetates, and nitrites) at a concentration greater than 0.1 mM (e.g., 0.5 mM to

In one embodiment, the pH is greater than 7 (eg, 8, 9, 10, 11, 12, 13). In one embodiment, the silver nanoplates are characterized by a maximum optical density wavelength of between 500 and 1500 nm (e.g., 700-1300, 810-830, 1000-1100 nm).

[0017] In various embodiments, the composition comprises silver nanoplates at least partially coated with a shell material comprising a polyvinyl polymer, wherein the average thickness of the shell material ranges from 1 nm to 50 nm (e.g., 5, 15, 40 nm). In one embodiment, the silver nanoplates have at least one edge between 10 nm to 500 nm in length (e.g., 25, 100, 250, 300 nm). [0018] Also disclosed is a kit comprising or consisting essentially of one or more containers containing nanoplates with an optical density greater than 10 cm.^-1 (e.g. 100 cm^-1, 1000 cm^-1 or more), a solution suitable for coating nanoplates with a metal oxide coating, and instructions for their use.

[0019] In various embodiments, the solution comprises silver nanoslabs at least partially coated with a silica coating, wherein the silver nanoplates have a maximum optical density greater than 10 cm.^-1 (e.g. 11-5000 cm^-1, 901 100 cm^-1 or more). In one embodiment, the silica coating has a coating thickness of between 2 to 100 nm (e.g., 10-70, 3090, 40-60 nm). In one embodiment, the solution comprises borate and optionally another water-soluble salt (e.g., sulfates, carbonates, chromates, phosphates, and sulfites, acetates, and nitrites) at a concentration greater than 0.1 mM (e.g., 0.1 mM to 10). mM) In one embodiment, the solution has a pH of greater than 7 (e.g., 9, 12, 13). In one embodiment, the silver nanoplates have a maximum of an absorption spectrum including a wavelength maximum of 500 nm to 1500 nm (e.g., 800-1400 nm). In one embodiment, a silica coating is applied to the outer surface of the silver nanoplatelets. In one embodiment, the shell contains an amino group or a mercaptyl group. Coatings additionally containing aluminum are also disclosed. Coatings containing

EP 2 906 286 Β1 bicarbonate. In one embodiment, the coating comprises poly (vinylpyrrolidone). Silver nanoplates with a thickness between 1 nm to 50 nm (e.g., 10-40, 15-25, 5-30) are also disclosed. Silver nanoplates are also disclosed having at least one edge with a length between 10 nm and

500 nm (e.g. 20-400, 50-250, 300-450 nm).

[0020] In some embodiments, the process for producing a super high optical density silver nanoplate solution comprises the steps of (i) adding a solution stabilizing chemical to the silver nanoplate or precursor reagent solution and (ii) increasing the concentration of the silver nanoplate to increase the optical density of the solution using centrifugation. , evaporation, filtering, dialysis or tangential filtration.

[0021] As used herein, the aspect ratio of the nanoplates ranges from 1.5 to 25 (e.g. 1.5-10, 1.5-5, 10-30, 25-50); and / or the nanoplates have an edge length between 10 nm to 250 nm (e.g. 25-180, 50-150 nm); and / or the nanoplates are triangular in cross section; and / or the nanoplates have a circular cross section. Within the scope of the present disclosure, the perimeter of the cross section of the nanoplate is 4 to 8 sides (e.g. 5, 6, 7). The solution of silver nanoplatelets is created using the seedmediated growth method. Also disclosed are one or more photoconversion methods, pH controlled photoconversion methods, thermal growth methods, and / or a solution comprising the shape stabilizing agent or agents and a silver source. This document uses chemical or biological agents and / or electromagnetic radiation and / or thermal energy or a combination of them to reduce the silver source. Herein, a solution of silver nanoplates is obtained by combining a reducer, shape stabilizer, light source, heat source and silver source.

[0022] Herein, an acid, base, or buffer (otherwise known as buffering agent) is added to the solution to change the pH of the solution. Within the scope of the present invention, a concentration stabilizing chemical is added to the solution before, during and / or after the preparation of the silver nanoplatelets. In this document, the concentration stabilizing chemical acts as a shape stabilizer. A stabilizing chemical in this document

EP 2 906 286 Β1 concentration acts as a reducing agent. As used herein, the concentration stabilizing chemical acts as an agent to alter the pH of the solution.

[0023] In one embodiment, the concentration stabilizing chemical consists of a water-soluble polymer and borate. The polymer is one or more derivatives of polyvinyl polymer and polyvinyl alcohol (PVA). In various embodiments, the PVA has a molecular weight of less than about 80,000 Daltons, from 80,000 Daltons to 120,000 Daltons, and / or greater than about 120,000 Daltons. In one embodiment, the polymer is poly (vinylpyrrolidone) (PVP). In various embodiments, the PVP has a molecular weight of less than about 20,000 Daltons, greater than about 20,000 Daltons, from about 20,000 Daltons to 60,000 Daltons, and / or greater than about 60,000 Daltons. In one embodiment, the polymer is derived from ethylene oxide.

[0024] In one embodiment, the polymer is polyethylene glycol (PEG). In various embodiments, the PEG has a molecular weight of less than about 5,000 Daltons, from 5,000 Daltons to 10,000 Daltons, and / or greater than about 10,000 Daltons. In one embodiment, the PEG contains a single functional group. In one embodiment, the PEG contains two functional groups. In some embodiments, the functional group or groups may be one or more groups including amine, thiol, acrylate, alkyne, maleimide, silane, azide, hydroxyl, lipid, disulfide, fluorescent and / or biotin molecules, or combinations thereof. In one embodiment, the functional group or groups may be one or more groups consisting of amino, thiol, acrylate, alkyne, maleimide, silane, azide, hydroxyl, lipid, disulfide, fluorescent molecules and / or biotin groups. In one embodiment, the concentration stabilizer is a carbohydrate derivative. In various embodiments, the polymer is a monosaccharide, disaccharide, oligosaccharide, polysaccharide, and / or dextran. In various embodiments, the dextran has a molecular weight of less than about 2,000 daltons (e.g., 500, 1,000, 1,500 daltons), from about 2,000 daltons to 5,000 daltons (e.g., 3,000,

ΕΡ 2 906 286 Β1

4000 Daltons), and / or greater than about 5,000 Daltons (e.g., 6,000, 8,000, 10,000 Daltons, or greater).

Also disclosed is a concentration stabilizing chemical that is one or more of the group consisting of phenol, monomeric phenol, dimeric phenol, trimeric phenol, polyphenol, and tannic acid, gum arabic coating, biological molecule, proteins, bovine serum albumin, streptavidins. , biotin, peptide, oligonucleotide, natural oligonucleotide, synthetic oligonucleotide, metal oxide or metalloid and / or silicon dioxide, wherein the silicon dioxide shell may have a thickness of between less than 1 to about 100 nm (e.g., 2-90, 5-25, 30-70). Within the scope of the present disclosure, a combination of stabilizers is used.

[0026] As used herein, the solvent may be one or more substances including water, alcohol, ethanol, isopropanol, t-butanol, a mixture of water and alcohol.

[0027] In one embodiment, the concentration of silver nanoplatelets is increased by a tangential filtration technique. In one embodiment, tangential filtration is performed on a tangential filtration membrane. In one embodiment, the tangential filtration membrane is made of cellulose ester or a blend of cellulose esters.

[0028] In various embodiments, the tangential filtration membrane is made of one or more compounds from the group consisting of polyethersulfone and / or polysulfone. In various embodiments, the tangential filtration membrane has a molecular weight cutoff of less than 10 kD (e.g., 1.5, 8 kD), ranging from 10 kD to 500 kD (e.g., 50, 250, 400 kD), greater than or equal to. about 500 kD (e.g., 750, 1000, 5000 kD or greater), or a pore size less than 0.05 µm (e.g. 0.01, 0.03 pm), ranging from 0.05 pm to 0.5 pm (e.g. 0.1, 0.25, 0.4 pm), and / or greater than about 0.5 pm (e.g. 1.0, 2, 5, 10, 100 pm).

[0029] In various embodiments, the silver nanoplate solution is concentrated to a final solution having an optical density greater than about 10 cm.^-1, greater than about 50 cm^-1, greater than about 75 cm^-1, greater than about 100 cm^-1 and / or greater than about 500 cm^-1(e.g. 100-1000, 100-2000 cm^-1).

at

EP 2 906 286 Β1

[0030] In one embodiment, the solvent of the concentrated solution is replaced by a tangential filtration technique. In one embodiment, the concentrated solution is treated with a tangential filtration technique to remove residual chemicals.

[0031] In various embodiments, a nanoparticle solution containing silver nanoparticles is coated with a polymer having an optical density greater than 100 cm.^-1 (e.g. 200, 500, 700, 1500 cm^-1, or more). In one embodiment, the silver nanoplate solution is incubated with the substrate. In one embodiment, the substrate is removed from the silver nanoplate solution and dried.

[0032] One embodiment of the present invention provides processes for preparing plasmonic nanoparticle solutions, for example silver nanoparticles, that are suitable for thermomodulating a target tissue area. Target tissue thermomodulation can be achieved by administering to a patient a composition comprising a plurality of plasmon nanoparticles such that an effective amount of plasmon nanoparticles is localized in the target tissue area domain followed by exposure of the target tissue area to the energy supplied from the excited source of surface plasmon resonance in the amount needed to inducing thermomodulation of the target tissue region domain. In various embodiments, the materials described herein are useful for performing targeted ablative or non-ablative tissue warming treatments. For example, described herein is a method of performing targeted ablative or non-ablative tissue warming treatments for treating a mammalian patient in need thereof, comprising (i) topically administering a plasmonic nanoparticle composition comprising silver nanoplates to the skin surface of a patient; (ii) providing a means of penetration that enables the plasmonic particles to pass from the surface of the skin to the component of the skin tissue; and (iii) light irradiation of the skin surface.

[0033] In several embodiments, the invention encompasses compositions that, when used with suitable modes of administration and induction,

EP 2 906 286 Β1 by using a light energy source make it possible to achieve a non-invasive or minimally invasive treatment of the skin and underlying tissues or other accessible tissue areas using nanoparticles. The use of plasmonic nanoparticle solutions with high optical density, e.g. silver nanoparticles, combined with their excitation with short laser pulses (e.g. Pulse widths from 0.1 ms to 1 s) can lead to steep heat gradients selectively delivering ablative or non-ablative thermal energy to the structures inside several cell layers in the vicinity of particle placement, e.g. to the sebaceous apparatus for acne treatment and pore size reduction targeted at the epidermis and skin layers for reconstruction treatments and low-profile remodeling of scars and hair follicles for permanent hair removal. Treatment may include, but is not limited to, hair removal, hair growth and regrowth, skin rejuvenation or restoration, acne removal or reduction, wrinkle removal, skin pores shrinkage, ablation of cellulite and other skin lipid build-up, wart and mycosis removal, thinning or removal of scars, including hypertrophic scars, atrophic scars and keloids), removal of pigmentation disorders (for example, salmon spots), removal of tattoos and / or skin inconsistencies (e.g., inconsistencies in texture, color, firmness, elasticity, hydration). Other therapeutic or prophylactic methods include, but are not limited to, treatment of excessive sweating, lack of sweating, Frey syndrome (gustatory sweating), Homer syndrome, Ross syndrome, actinic keratosis, follicular keratosis, dermatitis, vitiligo, dandruff, psoriasis, lichen. flat, eczema, alopecia, psoriasis, malignant or benign skin tumors.

BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Further objects, features and advantages of the invention (s) will become apparent from the following detailed description in conjunction with the accompanying figures representing illustrative embodiments of the invention in which a description of the drawings is provided below. The drawings are exemplary and are not intended to limit possible embodiments.

ΕΡ 2 906 286 Β1

Moreover, the listing of the embodiments with the given features does not exclude the embodiments having additional features, or other embodiments having other combinations of the features provided. In addition, features of one embodiment (e.g., shown in one of the figures) may be combined with the descriptions (and figures) of other embodiments.

Fig. 1 shows the optical spectrum of a solution of silver nanoplatelets produced by the photoconversion method. In one embodiment, these silver nanoplates after fabrication have a maximum optical density of less than 1 cm^-1 (e.g. about 0.8 cm^-1)

Fig. 2 shows the optical spectrum of a silver nanoplatelet solution produced by the seed-mediated growth method according to the present invention. Silver nanoplates after fabrication have a maximum optical density of less than 3 cm^-1.

Fig. 3A is an image of a silver nanoplatelet solution prepared by a photoconversion method obtained under a transmission electron microscope.

Fig. 3B is an image of a seed-mediated growth method of silver nanoplatelet solutions of the present invention obtained under a transmission electron microscope.

Fig. 4 is an optical spectrum of silver nanoplatelets without the addition of stabilizer and water-soluble salt before concentration and after concentration by tangential filtration.

Fig. 5 is a normalized optical spectrum of silver nanoplatelets without the addition of a stabilizer and water-soluble salt before concentration and after concentration by tangential filtration.

Fig. 6 is the optical spectra of the silver nanoplates of the present invention combined with polyvinyl alcohol and a water soluble salt before concentration and after concentration.

Fig. 7 is the normalized optical spectrum of the silver nanoplates of the present invention combined with polyvinyl alcohol and a water soluble salt before concentration and after concentration.

Fig. 8 shows the optical extinction spectra for the nanoplate solutions

ΕΡ 2 906 286 Β 1 silver ο high optical density processed by the methods described in the present invention.

Fig. 9 shows the steps of preparing silver nanoplates including fabricating silver nanoplatelets, adding stabilizers, concentrating the nanoplates, and optionally coating the nanoplates with silica.

DETAILED DESCRIPTION OF THE PREFERRED EXAMPLE

[0035] The present invention encompasses processes for preparing nanoparticle plasmon solutions containing silver nanoplates suitable for thermomodulating a target tissue area. For example, target tissue thermomodulation may be achieved by administering a plurality of plasmon nanoparticles to a patient in a manner that locates an effective amount of plasmon nanoparticles in the domain of the target tissue region. The target area of ​​tissue is exposed to energy supplied from an excited source of surface plasmon resonance. This energy is provided in an amount sufficient to induce thermomodulation of the target tissue area domain.

[0036] As used herein, the term "optical density" (OD) is synonymous with absorbance and is defined as the logarithmic ratio of radiation incident on a material to radiation transmitted through the material (OD = logs).₀(li / l₀) where h is the intensity of the transmitted light and l₀ is the intensity of the incident light). For solutions, the optical density is a function of the path length through the liquid sample and is expressed in cm^-1. In some cases, the optical density is expressed without the cm unit^-1 - for example in cases where the standard track length of 1 cm is used. In some of the traditional methods of producing silver nanoplatelets, the maximum optical density of silver nanoplates in post-synthetic solutions without additional treatment is typically less than 10 cm.^-1(e.g. 0.1-9.9 cm^-1, 1-9 cm^-1, 3-7 cm^-1, 1-5 cm^-1, and. or 5-10 cm^-1). However, according to the present invention, it is possible to produce silver nanoplatelets with increased optical density. As a rule, the optical density of solutions containing plasmonic particles, including silver nanoplates, is characterized by

ΕΡ 2 906 286 Β1 with the highest efficiency when their optical density is more than 10 cm^-1(e.g. 11-5000 cm '¹, 15-2000 cm '¹, 20-1000 cm '¹, 80-150 cm '¹, 90-110 cm '¹, 900 1100 cm^-1, 100 cm^-14, 1000 cm^-1 or more), are formulated with a pharmaceutical or cosmetic carrier and are stable for days, months, weeks or years without changes in the shape and / or properties of the particles, in one embodiment the optical densities of solutions containing plasmon particles, including silver nanoplates are larger than 10 cm^-1 (e.g. 115000 cm '¹, 15-2000 cm '¹, 20-1000 cm '¹, 80-150 cm '¹, 90-110 cm '¹, 900 - 1100 cm '¹, 100 cm '¹, 1000 cm '¹ or more), are formulated with a pharmaceutical or cosmetic carrier and are stable for days, months, weeks or years without changing the shape and / or properties of the particles. Described herein are carriers and compositions suitable for topical application to the skin of a mammalian patient such that the plasmon nanoparticles are present in an amount effective to selectively thermomodulate the selected skin component.

[0037] Described herein is a nanoparticle formulation made for application using a sponge applicator, cloth applicator, direct application by hand or gloved hand, spray, aerosol, vacuum suction, high pressure air flow or high pressure fluid flow using a roller, brush , flat surface, semi-flat surface, wax, ultrasound and other sonic forces, mechanical vibration, manipulation of the hair rollers (including by pulling or massaging), physical force, thermal manipulation, and / or other procedures. Such treatments using nanoparticle formulations are performed separately, in combination, sequentially, or in repeats of 1-24 times or more. Described herein is plasmonic nanoparticles selectively localized to a first skin component, where physical massage or pressure, ultrasound or heat increases the selective localization of the nanoparticles in said first skin component. Moreover, the described nanoparticles are selectively removable from skin components other than the said first component; such removal can be done with acetone, alcohol, water, air, peeling

ΕΡ 2 906 286 Β1 skin, chemical peeling, waxing or plasmonic compound reduction. Furthermore, nanoparticles are described with a coating layer intended to increase the solubility of the nanoparticles in the carrier and / or reduce their "stickiness" and accumulation in non-target areas. It is permitted herein to modify at least a portion of the outer surface of the nanoparticle to include a layer of a polymer, a polar monomer, a non-polar monomer, a biological compound, a metal (e.g. a metal thin foil, a metal composite, a metal oxide, or a metal salt), a dielectric, or a semiconductor. . In one embodiment, the external surface modification is polar, non-polar, electrically charged, ionic, basic, acidic, reactive, hydrophobic, hydrophobic, agonistic, and / or antagonistic in nature. Further, within the scope of the present disclosure, at least one dimension of the at least one nanoparticle in the plasmonic nanoparticle solution may be less than 50-100 nm (e.g. 1, 5, 10, 25, 40, 60, 75, 90 nm), and the surface of the nanoparticle can be coated with a matrix (e.g. silica) with a thickness of 10-100 nm or greater (e.g. 20, 50, 75, 150, 200 , 500 nm) to increase the size or the particles to 50-100 nm or more (e.g. 75, 80, 110, 140, 200, 800 nm). Increasing the size can increase the delivery of all nanoparticles to the target area (e.g. hair follicle, pores, skin, etc.) while limiting their delivery to the non-target area (e.g. leather).

[0038] The materials described herein are useful for performing targeted ablative or non-ablative tissue warming procedures, such as a method of performing targeted ablative or non-ablative tissue warming procedures for treating a mammalian patient in need of such surgery, comprising the steps of (i) topically administering a plasmon nanoparticle composition comprising silver nanoparticles to a patient's skin surface; (ii) providing a penetration means that enables the plasmon particles to pass from the surface of the skin to the component of the skin tissue; and (iii) light irradiation of the skin surface. In addition, it describes how

ΕΡ 2 906 286 Β1 wherein the light source is the excitation of mercury, xenon, deuterium or metal halide, phosphorescence, incidence, luminescence, light emitting diode or sunlight. Furthermore, a method is described wherein the penetration means comprises high frequency ultrasound, low frequency ultrasound, massage, iontophoresis, high pressure air flow, high pressure liquid flow, negative pressure, pretreatment by fractional photothermolysis or dermabrasion, or combinations thereof. Also described is a method wherein the irradiation includes light with a wavelength of light between about 200 nm to about 10,000 nm (e.g. 300-9000, 700-1300, 800-1200, 800-1300, 900-1100, 550-1100, 810-830, 1000-1100 nm), energy densities from about 1 to about 100 J / cm² (e.g. 5-20, 4070, 10-90), pulses ranging from about 1 femtosecond to about 1 second, and repetition rates from about 1 Hz to about 1 THz (e.g. 1-10, IOWO, 100-1000, 1000 -10000, 10000-100000 Hz or more).

[0039] Described herein are compositions which, when used in conjunction with appropriate modes of administration and excitation using a light source, achieve non-invasive or minimally invasive treatment of the skin and underlying tissues or other accessible tissue areas with nanoparticles. The use of plasmonic nanoparticle solutions with high optical density, e.g. silver nanoparticles, in combination with their excitation with short laser pulses (e.g. Pulse widths from 0.1 ms to 1 s) may lead to the formation of steep heat gradients selectively supplying ablative or non-ablative thermal energy to structures located in several layers of cells in the vicinity of particle placement, for example to the sebaceous apparatus. For the treatment of acne and reducing the size of pores, layers of the epidermis and skin. Regarding rejuvenation and low-profile remodeling of scars and hair follicles for permanent hair removal. Treatment may include, but is not limited to, hair removal, hair growth and regrowth, skin rejuvenation or renewal, acne removal or reduction, wrinkle removal, skin pores reduction, cellulite ablation and other lipid accumulations

EP 2 906 286 Β1 in the skin, removing warts and mycosis, reducing the thickness or removing scars, including hypertrophic scars, atrophic scars and keloids), removing pigmentation disorders (e.g. salmon spots), removing tattoos and / or skin inconsistencies (e.g. inconsistencies in texture, color, firmness, elasticity, hydration). Other therapeutic or prophylactic treatments include the treatment of excessive sweating, lack of sweating, Frey syndrome (gustatory sweating), Homer syndrome, Ross syndrome, actinic keratosis, follicular keratosis, dermatitis, vitiligo, dandruff, psoriasis, lichen planus, and eczema, among others. , alopecia, psoriasis, malignant or non-malignant skin tumors.

Silver nanoplates - physical description

[0040] This document describes nanoslabs, e.g. silver nanoplates, having the following dimensions along three principal axes: the axial length of two major axes is at least twice that of the shortest major axis, and the shortest major axis length is less than 500 nm (e.g. 450, 400, 350, 300, 250, 100, 150, 50, 30, 20, 10 nm). The "edge length" of a nanoplate is defined as the mean of the lengths along the two major major axes. The "thickness" of a nanoplate is defined as its length along its shortest major axis.

[0041] The ratio of the length of the plate edge to its thickness is referred to as the "aspect ratio". As used herein, the average aspect ratio of the silver nanoplates may be greater than 1.5, 2, 3, 4, 5, 7, 10, 20, 30, or 50, or any of these ranges. As used herein, the average aspect ratio of silver nanoplatelets may be from 1.5 to 25, from 2 to 25, from 1.5 to 50, from 2 to 50, from 3 to 25, and / or from 3 to 50.

[0042] Herein, the nanoplate may have an edge length of less than 500 nm, 250 nm, 200 nm, 150 nm, 100 nm, 80 nm, 60 nm, or 50 nm. As used herein, the nanoplate may have an edge length greater than 5 nm, 10 nm, 20 nm, 30 nm, 50 nm, or 100 nm. In various embodiments, the edge length ranges from 30 nm to 100 nm, from 20 nm to 150 nm, from 10 nm to 200 nm, from 10 nm to 300 nm. As used herein, the nanoplate may have a thickness of less than 500

ΕΡ 2 906 286 Β1 nm, 300 nm, 200 nm, 100 nm, 80 nm, 60 nm, 50 nm, 40 nm, 30 nm, 20 nm and / or nm and any of these ranges. As used herein, the nanoplate may have a thickness between 5 nm to 20 nm, 5 nm to 30 nm, 10 nm to 30 nm, 10 nm to 50 nm, 10 nm to 100 nm.

[0043] The silver nanoplates described herein can have a variety of cross-sectional shapes, including (but not limited to) circular, triangular, or a shape with any number of distinct edges. For example, nanoslabs can have the shape of circles, ovals, squares, rectangles, bars, stars, tubes, pyramids, prisms, triangles, branches, or flat surfaces. For example, nanoplates can have fewer than 20, 15, 10, 8, 6, 5, or 4 edges and / or any number of edges between 20 to 1. The nanoplates described herein can have 1 to 20, 15, 10, 8, 6, 5, 4, or 3 edges. For example, nanoplates can have more than 2, 3, 4, or 5 edges. For example, the silver nanoplates may have sharp corners or the corners may be rounded. For some of the silver nanoplatelets described herein, a number of different cross-sectional shapes of the sample may be present in the same sample. Within the scope of the invention, in solutions of silver nanoplates, more than 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90% of the particles in the solution are silver nanoparticles, while the remaining particles have other shapes including, but not limited to, cubic or irregular. In various embodiments, the silver nanoplate solution contains a percentage of the silver nanoplate, and the remaining particles in the solution have other shapes, including but not limited to spherical, cubic, or irregular. In various embodiments of the invention, the silver nanoplatelet solution comprises 5% to 100%, 10% to 50%, 50% to 100%, 30% to 60%, 60% to 100%, 40% to 70% , 70% to 100%, 50% to 80%, 80% to 100%, 60% to 90%, and / or 90% to 100% of the number of particles in solution that are silver nanoparticles, and the rest the particles have other shapes including, but not limited to, spherical, cubic, or irregular shapes. The claimed methods can increase the durability of silver nanoplatelets by allowing an increase in optical density while maintaining at least 50%, 60%, 70%, 80%, 90%, 95%, 98% or more of the percentage of silver nanoplatelets that do not change during the process.

EP 2 906 286 Β1 concentration. Methods are also described that can increase the durability of silver nanoplates to facilitate the increase in optical density while changing the shape of the nanoplate to a different shape (e.g. spherical, cubic and / or irregular) during the concentration process performed in less than 50%, 40%, 30 %, 25%, 20%, 10%, 5%, 3,%, 2%, 1% silver nanoplatelet. Described herein are nanoplates that can have one, two, or more planar sides. Pyramid-shaped nanoplates are also described.

[0044] Silver nanoparticles have distinct advantages over other shapes and plasmonic nanoparticle compositions. For example, the advantages of silver nanoplates over other plasmon nanoparticle shapes and compositions, including gold nano-envelope and gold nanorods, are associated with lower production costs (less reaction waste and lower material costs). In addition, silver nanoplates are characterized by a higher optical density to metal mass ratio than gold nanorods with random particle orientation in the solution and irradiation with non-polarized light, because the flat surface of the nanoplate resonates with both polarizations of the incident light. Moreover, the absorbance of silver nanoparticles is greater than the absorbance of gold nano-envelope with the same mass of metal, since a greater fraction of light is absorbed compared to the light scattered by the nanoparticle architecture relative to the nano-coating. For many applications, the described benefits in terms of cost and absorbance can only be realized in cases where silver nanoplates are stabilized at high concentrations for extended periods.

Fabrication of silver nanoplates

[0045] Modern techniques for the synthesis of nanoparticles have enabled the development of materials with unique optical properties for a wide range of applications including diagnostic, unclear and therapeutic applications. Silver nanoplates produced by traditional methods known in the art including photoconversion, pH controlled photoconversion, thermal growth and / or seed-mediated growth typically have optical densities ranging from 0.1 to 10 cm.^-1 (e.g. 0.1-9.9 cm^-1, 1-9 cm^-1, 3-7 cm^-1, 1-5 cm^-1, and / or 5-10 cm^-1). Many technologies require nanoplate solutions

ΕΡ 2 906 286 Β1 silver ο higher optical density. The present invention describes a new and non-obvious method to concentrate silver nanoplatelets and obtain silver nanoplate solutions with higher optical density. For example, such methods can increase the optical density of silver nanoplatelet solutions to values ​​above 10 cm^-1, 20 cm^-1, 30 cm^-1, 50 cm^-1, 80 cm^-1, 100 cm^-1, 150 cm^-1, 200 cm ' ¹, 300 cm^-1, 400 cm^-1, 500 cm^-1, 600 cm^-1, 700 cm^-1, 800 cm^-1, 900 cm^-1, and / or 1000 cm^-1, or larger.

[0046] Silver nanoplates can be produced by photoconversion (Jin et al. 2001; Jin et al. 2003), photoconversion under pH control (Xue 2007), thermal growth (Hao et al. 2004; Hao 2002; He 2008; Metraux 2005 ), growth on a template (Hao et al. 2004; Hao 2002), seed-mediated growth (Aherne 2008; Chen; Carroll 2003; Chen; Carroll 2002, 2004; Chen et al. 2002; He 2008; Le Guevel 2009; Xiong et al. 2007) or other methods. Other methods include methods in which silver nanoslabs are prepared from a solution containing a silver source together with one or more stabilizers, and chemicals, biologicals, mixing techniques, electromagnetic radiation, and / or heat are used to reduce the silver source.

[0047] Figure 1 shows the optical spectrum of silver nanoplatelets produced using a photoconversion method. The wavelength corresponding to the maximum of the optical spectrum (100) is 775 nm and corresponds to an optical density of 0.74 cm^-1. Figure 2 shows the optical spectrum of silver nanoplatelets produced by the seed-mediated growth method. The wavelength corresponding to the maximum of the optical spectrum (200) is 930 nm and corresponds to an optical density of 2.58 cm^-1. Figure 3A shows a transmission electron microscopy image of silver nanoplatelets produced using a photoconversion method. Figure 3A shows the transmission electron microscope image for silver nanoplatelets produced using the seed-mediated growth method.

[0048] In one embodiment in which the obtained nanoplates are concentrated by tangential filtration, the shape of the plurality of nanoplates may be deformed into nanospheres, which reduces the formulation efficiency and as evidenced by

The EP 2 906 286 Β1 is the increase in peak height at approx. 400 nm, which is the optical resonance peak of silver spherical nanoparticles. Figure 4 shows the optical density of the nanoplate solution in the absence of a concentration stabilizer before concentration (400) and after concentration (410). The optical resonance peak corresponding to the nanoplate plasmon resonance shifts from the value of 815 nm (420) to the value of 745 nm (430), which indicates a reduction in the mean edge length of the nanoplates.

[0049] Figure 5 shows the normalized diagram of the nanoplate in Figure 4. For this nanoplate solution, the peak intensity in the 700-850nm range correlates with the number of nanoplates in the solution. The intensity of the peak in the range of 400 nm is correlated with the number of spherical particles in the solution. Prior to concentration, the ratio of peak (520) height at longer wavelength to peak (540) height at shorter wavelength was 3. After concentration, the ratio of peak (530) height at longer wavelength to peak (550) height at shorter wavelength was 0.8. The change in ratio indicates changes in the shape of the nanoplates in the solution and a reduction in the number of nanoplates.

[0050] In one embodiment, the nanoplate solution may be stabilized. Fig. 6 shows the optical density of one embodiment of a solution of polyvinyl alcohol stabilized nanoplate in a borate solution (e.g. sodium borate, potassium tetraborate etc.). The wavelength peak corresponding to the peak of the nanoplates is the same for the unconcentrated (620) and concentrated (630) solutions, indicating that the edge length of the nanoplates remains the same before concentrating (600) and after concentrating (610)). Fig. 7 is a normalized spectrum indicating no change in the spectral shape of the peak before concentration (700) and after concentration (710), thus indicating that in one embodiment the surface coating is sufficient to prevent shape changes of the nanoparticles. Without surface protection, more than 10%, more than 20%, more than 30% or more than 50% of silver nanoplatelets can change the shape of the silver nanoplates. In other embodiments, when the nanoslabs are coated with a protective coating, the shape of the nanoplates changes in less than 20% or less than

EP 2 906 286 Β1

10% or less than 5% of silver nanoplates. In one embodiment, the spectrum of the nanoplate solution concentrated to a maximum optical density of -900 cm^-1 corresponds to that shown in Fig. 8.

[0051] In one embodiment, the silver nanoplates are made in a multistage process. In one embodiment, the steps to concentrate the nanoplates are shown in Fig. 9 and include preparing silver nanoplates (900), adding stabilizing agents (910), concentrating the nanoplates (920), and optionally coating the nanoplates with silica (930). In various embodiments, the steps may be performed in any order. In one embodiment, in a first step, silver nuclei are formed from an aqueous solution containing a reducing agent, stabilizer, water-soluble polymer, and silver salt. The reducer, stabilizer, and water-soluble polymer may be mixed prior to adding to the silver source. In the invention, the reducing agent used in the silver nucleation stage is sodium borohydride. In various embodiments, the reducing agent may be present at a concentration of at least 0.1mM, 1mM, or 3mM. In various embodiments of the invention, the reductant may be present at a concentration between 0.1 mM to 1 mM, 0.3 mM to 3 mM, 0.5 mM to 2 mM, 0.1 mM to 2 mM, 0, 1 mm to 10 mm.

[0052] The stabilizer can be a salt, polymer or biomolecule. In the present invention, the stabilizer is sodium citrate or other citrate derivative.

[0053] The water-soluble polymer may be a polyanionic polymer, including, but not limited to, a polymer derivatized with sulfonate groups, a polystyrene sulfonate derivative such as, for example, an inorganic polystyrene sulfonate salt or a monovalent polystyrene sulfonate salt. In the present invention, the water-soluble polymer is poly (sodium styrene sulfonate) (PSSS). In one embodiment, the PSSS has a molecular weight of between about 3 kDa to about 1000 kDa. In various embodiments, the PSSS has a molecular weight of between 3 kDa to 10 kDa, 5 kDa to 50 kDa, 10 kDa to 100k Da, 30 kDa to 300 kDa, 50 kDa, to 500 kDa, 100 kDa to 1000 kDa, from 300 kDa to 100 kDa, from 500 kDa to 1000 kDa.

EP 2 906 286 Β1

[0054] The silver salt may be any water-soluble silver salt, including, but not limited to, silver acetate, silver perchlorate, silver nitrate, silver trifluoroacetate, or silver trifluoromethanesulfonate. In the present invention, the salt of silver is silver nitrate.

[0055] In one embodiment, the silver nanoplatelet formulation step comprises growing silver nanoplatelet nuclei in an aqueous solution containing silver nuclei, an acid reducing agent, and a silver salt. In the present invention, the acid reducing agent is ascorbic acid. The silver salt used in the seed growth step for the silver nanoplatelet can be any water-soluble silver salt, including silver acetate, silver perchlorate, silver nitrate, silver trifluoroacetate, or silver trifluoromethanesulfonate, or combinations thereof. In the present invention, the silver salt is silver nitrate.

[0056] Within the scope of the present disclosure, the silver nanoplates can be blended at shear rates between 1 sec.^-1 up to 100,000 s^-1 (e.g. at least 10, 50, 100, 200, 300, 400, 500, 1000, 2000, 5000, 10,000, 20,000, 50,000, 75,000, 90,000 s'¹). Moreover, within the scope of the present disclosure, the silver nanoplates can be blended at shear rates between 10 sec^-1 up to 100 s^-1, from 50 p¹ up to 500 s'¹, from 100 s'¹ up to 300 s'¹, from 200 s'¹ up to 500 s'¹, from 100 s'¹ up to 400 s'¹, from 500 s'¹ up to 1000 s'¹, from 1000 s'¹ up to 10,000 s'¹, from 2000 s'¹ up to 5000 s'¹, from 1000 s' ¹ up to 2000 s'¹ and / or from 5000 s'¹ up to 10,000 s'¹.

Coating of silver nanoplatelets

[0057] In one embodiment, the silver nanoplates have particles absorbed or otherwise bound to the surface of the particles. The particles on the surface are the reagents or by-products of the reagents used in the synthesis. The object of the present invention is a partial or complete replacement of the particles attached to the surface of the silver nanoplates with other particles, which more fully protects the particles from changing shape during concentration. Another object of the invention is the use of a stabilizer that generates a lamellar shape and fixes the platelets during subsequent concentration in the manufacture.

ΕΡ 2 906 286 Β1

[0058] The stabilizers described herein include chemical or biological agents that physically adsorb (e.g., adsorb by nonmolecular bonding forces) to a surface, molecularly bind to the surface based on specific interactions (e.g., with a thiol or amine group), or surround the surface. this surface (e.g., metal oxide or metalloid oxide shell). Specific chemicals described herein include polymers such as polysulfonates. The stabilizing polymer described herein may be derivatized with sulfonates, or it is possible to use vinyl polymers, carbohydrates, ethylene oxides, phenols, and carbohydrates. Polymers of the invention include sodium polystyrene sulfonate, polyvinyl alcohol (PVA), poly (vinylpyrrolidone) (PVP), and polyethylene glycol (PEG) including PEG molecules containing one or more chemical (e.g., amine, thiol) groups , acrylate, alkyne, maleimide, silane, azide, hydroxyl, lipid, disulfide, fluorescent molecules or residues of biological molecules). The molecules described herein also include proteins, peptides, oligonucleotides, biotin, alkane thiols, lipoic and dihydrolipoic acid and derivatives of these acids, bovine serum albumin, streptavidin, neutravidin, wheat germ agglutinin, natural and synthetic oligonucleotides and peptides including synthetic peptides, including one or more chemical functional groups (e.g. amine, thiol, dithiol, phosphoracrylamidate, azide, dioxygenin, alkyne or biological moieties). Specific shell-forming chemicals of the invention include metal oxides SiO₂ and TiO₂. The stabilizers can be added before the preparation of the silver nanoplatelet, during the preparation of the silver nanoplate, or after the preparation of the silver nanoplate. An additional chemical agent disclosed herein is gum arabic. Within the scope of the present disclosure, the stabilizer can change the pH of the solution.

Carrier solutions

[0059] The silver nanoplates described herein can be made in aqueous solutions. Alternatively, it is possible to manufacture

ΕΡ 2 906 286 Β1 silver nanoplatelet in other solutions containing ethanol, isopropanol or organic solvents such as heptane, toluene or butanol.

[0060] In the present disclosure, an acid, a base, or a buffer to change the pH of the solution may be added to the solution before, during, or after adding the stabilizer. For example, a buffer, usually containing a water-soluble salt, may be added to the solution. In the present invention, the water-soluble salt is borate. In one embodiment, the water-soluble salt is sodium borate. One embodiment comprises suspending the nanoplates in a buffer containing sodium borate. In the present disclosure, the pH of the solution after the addition of the pH modifying agent may be greater than pH 6, pH 7, pH 8, pH 9 or pH 10. For example, the pH of the solution after addition of the pH modifying agent may be from pH 6 to pH 8, from pH 6 , 0 to pH 9, from pH 7 to pH 10, from pH 7 to pH 11, from pH 8 to pH 10, from pH 8 to pH 11, or from pH 7 to pH 12.

[0061] The combination of the nanoplate coating with the water-soluble salt in the buffer can stabilize the nanoplate formulation. For example, one of the salt components may interact with the nanoplate coating or a stabilizer to effect cross-linking and increase the durability of the coating, said cross-linking may involve the formation of non-covalent bonds (e.g. ionic bonds, hydrophobic interactions, hydrogen bonds or van der Waals forces, including dispersion interactions, dipole-dipole interactions or induced dipole-dipole interactions) and / or covalent bonds between the nanoplate surface, water-soluble salts and / or coating materials / stabilizers. The presence of a water-soluble salt in the buffer may change the binding affinity of the stabilizer or coating material for binding the nanoplate surface, e.g. by modifying the zeta potential and / or charges on the nanoplate surface. Optionally, the presence of a water-soluble salt in the buffer may alter the binding affinity of the stabilizer or coating material for binding its own molecules through covalent or non-covalent interactions. For example, the presence of water-soluble salts alters the bond between the stabilizer and the surface of the particle through physical adsorption to the surface

Particle via stabilizer. In a further example, the presence of the water-soluble salts alters the bonds between the polymer molecules by binding them to the stabilizer or coating material units and lowering the free energy required to align the coating material molecules on or around the nanoplate surface. For example, the coating of the nanoplate can be polymeric and its cross-linking can produce a viscoelastic gel surrounding all or part of the nanoplate. In another example, the stabilizer is mixed with a buffer containing a water-soluble salt, and the stabilizer and soluble salt component bind the surface of the nanoplate. In the present invention, a polyvinyl-based polymer, for example polyvinyl alcohol or polyvinylpyrrolidone, is mixed with a salt of boric acid, for example sodium borate. Poly (vinyl alcohol) and borate can form gels by bonding to each other through hydrogen bonds (Schultz 1969). In one embodiment, Figure 6 and Figure 7 show the stabilizing effect of polyvinyl alcohol and sodium borate on silver nanoplates prior to concentrating the solution to maintain the shape of the nanoparticles.

Surface stabilization

[0062] The stabilizers can be solid or liquid formulations added to the silver nanoplatelet solutions described herein. The stabilizers have an affinity to the surface of silver nanoplatelets and are able to bind to this surface of the plates over a wide range of relative concentrations. For example, it is possible for particles bound to the nanoplatelet surface to be displaced by stabilizer particles. Alternatively, it is possible for the stabilizer molecule, for example a polymer, to covalently bind a carbon atom on the surface of the nanoplate. The polymer coating may extend over the entire outer surface of the silver nanoplate or over a portion of it. For example, one type of polymer or multiple types of polymers can be coated with at least 5%, 10%, 15%, 20%, 25%, 50%, 75%, 80%, 90%, 95%, 99%, 99.9 % or more than 99.9% of the outer surface of the silver nanoplate. In the present invention, the stabilizer is added because the silver nanoplatelet is synthesized. In this way, compositions are formed containing polymer-coated silver nanoplates which enable the preparation of compositions containing these

ΕΡ 2 906 286 Β1 solutions ο optical density greater than 10 cm^-1; these solutions can be obtained by concentration or purification of polymer coated silver nanoparticles present in a more dilute solution. In the present disclosure, the stabilizers may be added to the silver nanoplatelet solution in which they were prepared. Alternatively, it is possible to wash the nanoplate solution or remove residual reagents by other means. For example, the solution in which the nanoplate suspension is formed may be replaced one or more times with one or more solutions, for example to wash the nanoplates or to change the pH of the solution prior to adding the stabilizers. Kits containing nanoplates in solution with an optical density greater than cm in one or more containers are also described^-1 and a solution containing a metal oxide or metal oxide precursor suitable to surround the nanoplate surface with a coating (or envelope) of the metal oxide. Preferably, such containers are provided with instructions for their use. The kit may contain nanoplates with a coating comprising a polyvinyl polymer. The polyvinyl polymer may contain a salt of boric acid. The stabilizer coated nanoplates are characterized as described herein or as otherwise known in the art, for example using particle analyzers or emission detectors, for example in NMR assays, Fourier transform spectroscopy, mass spectroscopy or the like.

[0063] After the stabilizer is added, the mixture of the stabilizer and the silver nanoplatelet can be subjected to a number of different processes such as heating, boiling, refluxing, rotary evaporation, vacuum stripping, mixing, magnetic dipole mixing, mechanical stirring, and mechanical stirring. using homogenizers, shaking, microfluidization, cooling and freezing.

Rinsing and concentration

[0064] After the stabilization step is completed, the silver nanoplates can be washed to remove any remaining reagents or to replace the solution with another solution. Solution replacement can be accomplished by dialysis, centrifugation, filtration, or tangential filtration (or flow filtration). For example, the number of volumes

ΕΡ 2 906 286 Β1 of the rinsing medium listed for a given sample can be zero, 1,2, 3,

4, 5, 1 and 5.5 to 10, 10 to 20 or more than 20 volumes inclusive.

[0065] Nanoparticle solutions with optical densities greater than 10 cm^-1 (e.g. 11-5000 cm '¹, 15-2000 cm '¹, 20-1000 cm '¹, 80-150 cm '¹, 90-110 cm '¹, 900 - 1100 cm^-1, 100 cm^-1, 1000 cm^-1 or more) can be made based on centrifugation, evaporation, filtering, dialysis or tangential filtration. In one embodiment of the present invention, tangential filtration is used as the process for concentrating the silver nanoplatelet solution. The used filter membrane can be made of a wide variety of materials. For example, specific filter membrane materials of interest may include cellulose esters, polysulfone, and polyethersulfone. In various embodiments, the filter membrane used may have pores with a molecular weight cutoff of less than 10 kD, ranging from 10 kD to 500 kD or greater than 500 kD, and / or with pore sizes less than 0.05 µm, ranging from 0.05 pm to 0.5 pm or above 0.5 pm. In various embodiments, the filter membrane may have pores with a molecular weight cutoff ranging from 10 kD to 100 kD, 10 kD to 500 kD, 20 kD to 500 kD, 20 kD to 250 kD, and / or pores ranging from 0.02 to 0.1 pm, from 0.05 to 0.2 pm, from 0.05 to 0.5 pm, from 0.10 to 0.2 pm, from 0.1 to 0, 5 pm. Tangential filtration can also be used to replace the solvent in which the silver nanoplates are suspended. In various embodiments, specific solvents of interest include water and alcohols (e.g., t-butanol, ethanol, and isopropanol), as well as other polar and non-polar solvents. In addition, tangential filtration can be used to remove residual chemicals. Fig. 8 shows an example of an embodiment of a nanoplate solution concentrated to a maximum optical absorbance of 930 cm '¹.

[0066] In various embodiments, the concentration of the silver nanoplatelet solution is increased until a final solution having an optical density greater than about 10 cm is reached.¹, greater than about 50 cm^-1, greater than about 75 cm^-1, greater than about 100 cm^-1, greater than about 500 cm^-1 and / or greater than about

ΕΡ 2 906 286 Β1

1000 cm^-1. In various embodiments of the invention, the concentration of the silver nanoplatelet solution is increased until the final solution is reached with an optical density ranging from 10 cm^-1 up to 100 cm^-1, from 30 cm^-1 up to 300 cm^-1, from 50 cm¹ up to 500 cm^-1, from 100 cm^-1 up to 1000 cm^-1, from 300 cm^-1 up to 3000 cm^-1 or from 500 cm^-1 up to 5000 cm^-1. In one embodiment of the invention, the concentration of the silver nanoplatelet solution is increased to above 10⁶, 10⁷, 10⁸, 10⁹, 10¹⁰, 10¹¹, 10¹² or 10¹³ particles per milliliter. In various embodiments, the concentration of the silver nanoplatelet solution is raised to between 10⁶ up to 10¹³, from 10⁷ up to 10¹³, from 10⁸ up to 10¹³, from 10⁹ up to 10¹³, from 10¹⁰ up to 10¹³, from 10¹¹ up to 10¹³or from 10¹² up to 10¹³ particles per milliliter. In various embodiments, the concentration of silver is greater than 0.1, 1.0, 2, 4, 5, 7, 8, 9 and / or 10 mg / ml. In various embodiments, the silver concentration is 0.1 to 1.0, 0.3 to 3.0, 0.5 to 5.0, 1.0 to 10.0, 3.0 to 30, 0, 5.0 to 50.0, 10.0 to 200.0, 1.0 to 200.0, 1.0 to 500.0, or 10.0 to 500.0 mg / mL.

Silica coatings and shells

[0067] In one embodiment, the concentrated silver nanoplates are covered with silica shells. The coating may extend over the entire outer surface of the silver nanoplate or over a part of it. For example, silica can be coated with at least 5%, 10%, 15%, 20%, 25%, 50%, 75%, 80%, 90%, 95%, 99%, 99.9% or over 99.9 % of the outer surface of the silver nanoplate. The concentrated plates can be mixed with alcohol (e.g., ethanol or isopropanol). In one embodiment, an aminosilane or mercaptosilane is added to the solution to bind the silane particles to the surface of the nanoplates. Binding of silane molecules to the nanoplate surface is specific for a given coating on the nanoplate surface. Some nanoparticle coatings that stabilize nanoplates during processing are not compatible with the formation of silica coatings. In one embodiment, the surface of the nanoplates is coated with a molecule that has an affinity for the silane molecules in solution. In one embodiment, a polyvinyl-based polymer, for example polyvinyl alcohol or polyvinylpyrrolidone, is bonded to the nanoplate surface prior to addition of the silane particles. In other embodiments, the surface

The ΕΡ 2,906,286 Β1 polyvinyl-based polymer is complexed with borane prior to the addition of the silane particles. In other embodiments, mercaptohexadecanoic acid, mercaptoundecanoic acid, or other thiol-containing acids are adhered to the nanoplate surface. After the first silane particles bind the nanoplate surface, a further amount of silane can be added to the solution in the presence of a base to form a silica shell. In one embodiment, silica coated nanoplates can be transferred to water and concentrated by a method such as, for example, tangential filtration.

[0068] The object of the present invention is to prepare a solution which is a concentrated solution of silver nanoplatelets coated with silica coatings. In the present disclosure, the maximum solution optical density when measured using a 1 cm cuvette may be greater than 10, 20, 50, 100, 500, or 1000. For example, the maximum optical density of a solution when measured using a 1 cm cuvette may be in the range 10-100, 20-200, 30-300, 50-500, 100-1000, 200-1000, 300-1000, 500 -1000 and / or 200-2000 or any combination of these ranges. In the present disclosure, the concentration of silver can be greater than 0.1 mg / ml, 1 mg / ml, or greater than 10 mg / ml. For example, the concentration of silver can range from 0.1 to 1.0, 0.3 to 3.0, 0.5 to 5.0, 1.0 to 10.0, 3.0 to 30.0, 5.0 to 50.0, 10.0 to 200.0, 1.0 to 200.0, 1.0 to 500.0, and / or 10.0 to 500.0 mg / ml or any combination of the above ranges. In one embodiment, the thickness of the silica shell is from 1 to 100 nm, such as from 5 to 50 nm. In other examples, the thickness of the silica shell ranges from 3 to 20 nm, 5 to 20 nm, 10 to 20 nm, 10 to 50 nm, 10 to 100 nm, 1 to 10 nm, 3 to 30 nm. nm, 5 to 50 nm and / or 5 to 100 nm, or any combination of these ranges. The silica shell can be formed from a mixture of silanes including, but not limited to, aminopropyltriethoxysilane, mercaptopropyltriethoxysilane, and tetraethyl orthosilicate. The silica shell may contain nitrogen or sulfur atoms. The silica shell may contain amine or mercaptyl residues. The silica shell may contain aluminum or sodium atoms.

[0069] In another embodiment, the solution comprises a buffer containing

EP 2 906 286 Β1 borate and optionally another water-soluble salt (e.g. one or more salts from the group consisting of sulfates, carbonates, chromates, phosphates, and sulfites, acetates, and nitrites) at a concentration greater than 0.1 mM, 0.1 mM, or 10.0 mM) For example, the concentration of a water-soluble salt can be be in the range 0.1 mM to 1 mM, 0.3 mM to 3 mM, 0.5 mM to 5 mM, 1 mM to 10 mM, 1 mM to 30 mM, 1 mM to 50 mM, from 1 mM to 1000 mM, and any combination of these ranges. The solution may have a wavelength corresponding to the maximum absorption ranging from 500 nm to 1500 nm, from 500 nm to 1200 nm, from 500 nm to 1000 nm, from 600 nm to 1200 nm, from 700 nm to 1200 nm, from 700 nm to 1500 nm, 700 nm to 900 nm, and / or 900 to 1100 nm, or any combination of these ranges.

Storage

[0070] Herein, the concentrated particles can be stored at temperatures below -10, 0, 4, 6, 10, or 20 degrees Celsius. For example, the particles can be frozen and dried under vacuum. For example, the particles may be dried by freeze drying or under supercritical conditions. An additional stabilizer or a cryoprotecting agent may be added to the solution prior to heat drying or lyophilizing the particles.

Composites

[0071] In one embodiment of the invention, high optical density silver nanoplatelet solutions are bonded to a substrate, where the substrate comprises fibers. Other types of substrates disclosed include cloth, mesh, bandages, socks, onucas, other garments, sponges, high porosity substrates, particles with edge lengths greater than 1 micron, granules, hair, leather, paper, absorbent polymers, foams, wood, cork, smooth surfaces, rough surfaces, biocompatible media, filters or medical implants. Silver nanoplatelet solutions with concentrations of at least 1 mg / ml, 10 mg / ml and / or 100 mg / ml can be incubated with the medium. For example, the concentration of silver nanoplatelet incubated with the medium can be 0.1 to 1.0, 0.3 to 3.0, 0.5 to 5.0, 1.0 to 10.0, 3.0 up to 30.0, 5.0 to 50.0, 10.0 to 20.0, 5.0 to 50.0, 3.0 to 50.0, 1.0 to 100.0, 10.0 to 100.0, 20.0 to 100.0, 30.0 to 100.0 mg / mL. In another

EP 2 906 286 Β1 for example, solutions of silver nanoplatelet incubated with the medium may contain from 10⁶ up to 10¹³, from 10⁷ up to 10¹³, from 10⁸ up to 10¹³, from 10⁹ up to 10¹³, from 10¹⁰up to 10¹³, from 10¹¹ up to 10¹³, from 10¹² up to 10¹³ or more than 10¹³ particles per milliliter. In another example, the silver nanoplates may be prepared with an optical density of at least 100, 300, 500, 1000, and / or 2000 cm before incubating with the substrate.^-1. For example, silver nanoplates can be prepared with an optical density of 100-200, 100-300, 100-500, 100-1000, 2001000, 300-1000, 500-1000, or 200-2000. In another part of the disclosure, the substrate is treated with chemicals to enhance the bonding of the substrate by nanoplates. For example, the substrate can be functionalized with a molecule that causes a positive or negative surface charge. In another part of the disclosure, the pH of the incubation solution is selected to optimize binding. In another part of the disclosure, the silver nanoplates cover at least 5%, 10%, 20%, 30%, 50%, or 75% of the substrate; for example, nanoplates can cover 5% to 10%, 10% to 100%, 10% to 50%, 50% to 100%, 30% to 100%, 30% to 70%, 40% % to 80%, 50% to 90%, 60% to 100%, 70% to 100%, 80% to 100%, 90% to 100%, 0% to 5%, 0% up to 10%, 0% to 20%, 0% to 30%, or 0% to 50% of the substrate. In another part of the disclosure, other solvents or chemicals are added to the incubation solution. In another part of the disclosure, a biological linker (e.g., antibodies, peptides, DNA) is used to bind high optical density silver nanoplatelets to a substrate surface. Incubation herein may be less than 1 minute, 5 minutes, 20 minutes, 60 minutes, or 120 minutes. . For example, the incubation time can be 0 to 1 minute, 1 minute to 120 minutes, 5 minutes to 120 minutes, 20 minutes to 120 minutes, 60 minutes to 120 minutes, 5 minutes to 60 minutes, 10 minutes up to 60 minutes, 20 minutes to 60 minutes, 0 minutes to 10 minutes, 0 minutes to 20 minutes, 0 minutes to 5 minutes.

[0072] Within the scope of the present disclosure, the medium may be separated from the incubation solution and dried. The substrate may be air-dried, heat-dried, freeze-dried or in a supercritical environment. In another part of the disclosure, the dried substrate may be further processed

ΕΡ 2 906 286 Β1 treatment by impregnating it with another material, painting it with another material or exposing it to another material in the gas phase.

[0073] The specifications and examples set forth herein should be considered as disclosing only some embodiments of the invention, and the scope of the invention is defined by the following claims.

[0074] The subject matter described herein may be made in other specific forms without departing from the scope or essential characteristics of the subject matter of the disclosure. Thus, the embodiments described above are to be considered illustrative in all respects and not intended to limit the scope of the invention. While the embodiments may be subject to various modifications and be in alternative forms, specific examples of such embodiments are shown and described in the drawings below. It should be understood, however, that the scope of the invention should not be limited by the specific forms or methods disclosed, on the contrary: the invention is intended to include all modifications, equivalents, and alternatives within the meaning and scope of the particular embodiments described herein and the appended claims. Any methods described in this document do not need to be performed in the order presented.

[0075] The methods disclosed herein include specific actions by practicing physicians, however, these actions may also include express or implied instructions from third parties. For example, activities such as "identifying a target region of skin tissue" also include activities such as "instructing how to identify a target region of skin tissue."

[0076] The ranges given in the present disclosure also include any common parts, sub-ranges, and combinations of ranges. Words such as "up to", "at least", greater than, "less than" from ... to "etc. mean ranges including the given value. Values ​​prefixed with "about", "approximately" or "substantially" include the given values. For example, "about 3mm" includes "3mm". Deadlines

For the purposes of this disclosure, "about", "approximately" or "substantially" corresponds to an amount or property that is close to the stated value or property and still fulfills the desired function or result. For example, the terms "about", "approximately", or "substantially" can refer to values ​​that range from plus or minus 10%, plus or minus 5%, plus or minus 1%, plus or minus 0.1%, and plus or minus 0. 0.01% of the specified amount or property.

Examples

[0077] The following descriptions of specific examples are illustrative only and are not intended to limit the scope of the invention disclosed herein.

Example 1: Silver nanoplates

[0078] Silver nanoplates were synthetically prepared from silver nuclei prepared by reducing silver nitrate with sodium borohydride in the presence of tribasic sodium citrate and sodium polystyrenesulfonate under aqueous conditions. Preparation of silver seeds: 21.3 ml of an aqueous solution of tribasic sodium citrate with a concentration of 2.5 mM was stirred with a magnetic stirrer. Then, 1 ml of sodium polystyrene sulfonate (PSSS) at a concentration of 2 g / L was prepared in a separate beaker. Then, by dissolving the silver nitrate in water, 21.3 ml of a 0.5 mM solution of this salt was prepared. After the above solutions were prepared, 1.33 ml of a 0.5 mM sodium borohydride solution was prepared in water at 4 ° C. The borohydride and PSSS solutions were then added to the citrate beaker and allowed to mix. The silver nitrate solution was then pumped into the citrate solution at a rate of 100 ml / min using a peristaltic pump. The resulting seed solution was allowed to stand overnight with stirring at room temperature. The silver nanoplates were prepared by mixing 1530 ml of Milli-Q water with 35 ml of a 10 mM ascorbic acid solution. After the solution was properly mixed, the silver seed was added to the reactor. 353 ml of a 2 nM silver nitrate solution was pumped into the reactor at a rate of 100 ml / min. The reaction mixture was stirred for two hours. Analysis under an electron microscope

The ΕΡ 2 906 286 Β1 transmission line showed that 70% of the particles were nanoplates. The optical density of the solution was 2.8 cm.¹.

Example 2: Concentrated silver nanoplates

[0079] 15 L of silver nanoplates with a maximum optical density of about 5 cm^-1 mixed with 3.5 g of polyvinyl alcohol (PVA) and sodium borate, concentrated by tangential filtration on a polysulfone membrane with a cut-off of 500 kD and an area of ​​3100 cm². The solution was concentrated for about 90 minutes and the final volume of the solution was reduced from 15 I to 0.5 L. The optical density of the silver nanoplatelet solution increased to about 150 cm.^-1. Thus, according to one embodiment of the invention, a method of increasing the optical density of a silver nanoplatelet solution from 5 cm^-1 up to 150 cm^-1 (i.e. an approx. 30-fold increase in optical density) includes the steps of adding PVA and sodium borate to the silver nanoplatelets, and then concentrating the solution using the tangential filtration technique.

Example 3: Concentrated silver nanoplates

[0080] In one example of concentrating 1.2 I silver nanoplatelets, silver nanoplates with a maximum optical density of about 4 cm^-1 it was mixed with 4 I of absolute ethanol and about 49 ml of ammonium hydroxide solution. 0.6 ml of dilute aminopropyltriethoxysilane (APTES) was added to the solution. After 15 minutes of incubation, 6.5 ml of tetraethylorthosilicate solution (TEOS) was added. After 24 hours, 1 L of the solution was concentrated on a polysulfone membrane for tangential filtration with a cut-off of 500 kD and a surface area of ​​1050 cm.². The final volume of the solution was reduced to 150 ml, thus increasing the optical density of the silver nanoplatelet solution to about 40 cm^-1. Thus, according to one embodiment of the invention, a method of increasing the optical density of a solution of silver nanoplatelets from 4 cm^-1 up to 40 cm^-1 (i.e. by approx. 10-fold increase in optical density) includes the steps of adding anhydrous ethanol, a solution of ammonium hydroxide, aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) to silver nanoplatelets, and concentration of the solution by tangential filtration.

Example 4: Nanoplates with a silica shell

[0081] A silica shell was formed on the surface of the coated

ΕΡ 2 906 286 Β1 poly (vinylpyrrolidone) (PVP) silver nanoplatelets with plasmon resonance at a wavelength of 800 nm (edge ​​length ~ 75 nm). 400 ml of a solution of plasmon resonance silver nanoplatelets coated with poly (vinylpyrrolidone) at a wavelength of 800 nm at a concentration of 2 mg / ml (optical density 20 cm)^-1) was added while stirring to 2.3 L reagent grade ethanol and 190 mL Milli-Q water. Thereafter, 4.3 ml of dilute aminopropyltriethoxysilane (215 µl APTES in 4.085 ml isopropanol) was added to the solution, followed immediately by 44 ml of 30% ammonium hydroxide. After 15 minutes of incubation, 31 ml of diluted tetraethylorthosilicate (1.55 ml TEOS in 29.45 ml isopropanol) was added to the solution. The solution was allowed to stir overnight. The nanoplates were then centrifuged on an ultracentrifuge at 17,000 RCF for 15 minutes and redissolved in Milli-Q water, and the centrifugation and dissolution procedure was repeated twice. The thickness of the silica shell was 15 nm. The optical density of the concentrated material was 2040 cm^-1.

Example 5:

[0082] 40 ml of a solution of concentrated silver nanoplatelet with an optical density of 40, stabilized with polyvinyl alcohol and sodium borate was centrifuged for 30 minutes at a relative centrifugal force of 3000 RCF. The supernatant was removed and the pellet was resuspended in an ultrasonic bath. The concentrated silver nanoplates had an optical density above 900 as shown in Figure 8.

Example 6: Concentrated nanoplates on a substrate

[0083] 5 ml of a 1000 optical density silver nanoplate solution was added to a 3 "x 3" scrap of absorbent fabric (Absorber Synthetic Drying Chamois, Clean Tools). The substrate was then allowed to air dry. After drying, the silver nanoplates were attached to the surface of the fabric and did not detach from it after the fabric was subsequently wetted and the water was removed under pressure.

References [0084]

Aherne, DL, DM; Gara, M .; Kelly, JM, 2008: Optical Properties and

EP 2 906 286 Β1

Growth Aspects of Silver Nanoprisms Produced by Highly Reproducible and Rapid Synthesis at Room Temperaturo. Advanced Materials, 18, 2005-2016.

Chen, S., and DL Carroll, 2003: Controlling 2-dimensional growth of silver nanoplates. Self-Assembled Nanostructured Materials Symposium (Mater. Res. Soc. Symposium Proceedings Vol. 775), 343-348 | xiii + 394.

Chen, SH, and DL Carroll, 2002: Synthesis and characterization of truncated triangular silver nanoplates. Nano Letters, 2, 1003-1007.

Chen, S., and DL Carroll, 2004: Silver nanoplates: Size control in two dimensions and formation mechanisms. Journal of Physical Chemistry B, 108, 5500-5506.

Chen, SH, ZY Fan, and DL Carroll, 2002: Silver nanodisks: Synthesis, characterization, and self-assembly. Journal of Physical Chemistry B, 106, 10777-10781.

Hao, E., GC Schatz, and JT Hupp, 2004: Synthesis and optical properties of anisotropic metal nanoparticles. Journal of Fluorescence, 14, 331-341.

Hao, EK, KL; Hupp, JT; Schatz, GC, 2002: Synthesis of Silver Nanodisks using Polystyrene Mesospheres as Templates. J Am Chem Soc, 124,15182-15183.

He, XZ, X .; Chen, Y; Feng, J., 2008: The evidence for synthesis of truncated silver nanoplates in the presence of CTAB. Materials Characterization, 59, 380-384.

Jin, R., Y. Cao, CA Mirkin, KL Kelly, GC Schatz, and JG Zheng, 2001: Photoinduced Conversion of Silver Nanospheres to Nanoprisms. Science, 294, 1901-1903.

Jin, R., YC Cao, E. Hao, GS Metraux, GC Schatz, and CA Mirkin, 2003: Controlling anisotropic nanoparticle growth through plasmon excitation. Nature, 425, 487.

EP 2 906 286 Β1

Le Guevel, XW, FY; Stranik, O .; Nooney, R .; Gubała, V .; McDonagh, C .; MacCraith, BD, 2009: Synthesis, Stabilization, and Functionalization of Silver Nanoplates for Biosensor Applications. J Phys Chem C, 113, 16380-16386.

Metraux, GSM, CA; 2005: Rapid Thermal Synthesis of Silver Nanopńsms with Chemically Tailorable Thickness. Advanced Materials, 17, 412-415.

Schultz, RK; Myers, RR; 1969: The Chemorheology of Poly (vinyl alcohol) -Borate Gels. Macromolecules, 2, 281-285.

Xiong, YJ, AR Siekkinen, JG Wang, YD Yin, MJ Kim, and YN Xia, 2007: Synthesis of silver nanoplates at high yields by slowing down the polyol reduction of silver nitrate with polyacrylamide. Journal of Materials Chemistry, 17, 2600-2602.

Xue, CM, CA, 2007: pH-Switchable Silver Nanoprism Growth Pathways. Angew Chem Int Ed, 46, 2036-2038.

ΕΡ 2 906 286 Β1