US-20260124324-A1 - PHOTOCLICK CHEMISTRY OF SILK FOR TEMPORARY UV TATTOOS

US20260124324A1US 20260124324 A1US20260124324 A1US 20260124324A1US-20260124324-A1

Abstract

Silk photoclick tattoo inks include modified silk nanoparticles including modified silk fibroin functionalized with a plurality of first photoclick chemistry pair moieties, wherein the modified silk nanoparticles are biocompatible and bioresorbable; and photoclick chromophores including a second photoclick chemistry pair moiety, wherein the first photoclick chemistry pair moiety and the second photoclick chemistry pair moiety undergo a known photoreaction when illuminated with light having a predetermined wavelength for a predetermined exposure length and a predetermined exposure intensity, thereby covalently bonding at least a portion of the photoclick chromophores to at least a portion of the modified silk nanoparticles, wherein the silk photoclick tattoo ink is safe for human use as a tattoo ink.

Inventors

Fiorenzo G. Omenetto
Nicholas Ostrovsky-Snider

Assignees

TRUSTEES OF TUFTS COLLEGE

Dates

Publication Date: 20260507
Application Date: 20250908

Claims (20)

1 . A silk photoclick tattoo ink comprising: modified silk nanoparticles comprising modified silk fibroin functionalized with a plurality of first photoclick chemistry pair moieties, wherein the modified silk nanoparticles are biocompatible and bioresorbable; and photoclick chromophores comprising a second photoclick chemistry pair moiety, wherein the first photoclick chemistry pair moiety and the second photoclick chemistry pair moiety undergo a known photoreaction when illuminated with light having a predetermined wavelength for a predetermined exposure length and a predetermined exposure intensity, thereby covalently bonding at least a portion of the photoclick chromophores to at least a portion of the modified silk nanoparticles, wherein the silk photoclick tattoo ink is safe for human use as a tattoo ink.
2 . (canceled)
3 . (canceled)
4 . A method of generating a silk photoclick tattoo in a subject's skin, the method comprising the following steps: a) administering a silk photoclick tattoo ink to an area of the subject's skin, the silk photoclick tattoo ink comprising modified silk nanoparticles and photoclick chromophores, the modified silk nanoparticles comprising modified silk fibroin functionalized with a plurality of first photoclick chemistry pair moieties, wherein the modified silk nanoparticles are biocompatible and bioresorbable, the photoclick chromophores comprising a second photoclick chemistry pair moiety; b) exposing the silk photoclick tattoo ink within the area to light having a predetermined wavelength for a predetermined exposure length and a predetermined exposure intensity, thereby initiating a known photoreaction and covalently bonding at least a portion of the photoclick chromophores to at least a portion of the modified silk nanoparticles, the administering and exposing of steps a) and b) thereby generating the silk photoclick tattoo in the area of the subject's skin.
5 . The method of claim 4 , the method further comprising the following steps: c) administering the silk photoclick tattoo ink to a delimited area of the subject's skin; d) preventing the silk photoclick tattoo ink within the delimited area from undergoing the known photoreaction; and e) optionally waiting a bioresorption length of time, the administering, preventing, and optionally waiting of steps c), d), and e) generating an absence of the silk photoclick tattoo in the delimited area.
6 . The method of claim 5 , wherein the preventing of step d) includes applying a photomask to the delimited area, wearing a protective sheath covering the delimited area, selectively illuminating, or a combination thereof.
7 . The method of claim 5 , the method comprising the following step: e) waiting the bioresorption length of time.
8 . The method of claim 7 , wherein the bioresorption length of time is between 1 month and 1 year.
9 . The method of claim 4 , the method further comprising administering a selective degradation agent to at least a portion of the area, thereby dissolving at least a portion of the silk photoclick tattoo ink within the at least a portion of the area, thereby reducing a visibility of the silk photoclick tattoo within the at least a portion of the area.
10 . The method of claim 9 , wherein the selective degradation agent is an enzymatic agent.
11 . The method of the claim 10 , wherein the enzymatic agent is protease XIV, trypsin, bromelain, papain, or a combination thereof.
12 . The method of claim 4 , wherein the administering of step a) comprises administering via a dissolvable microneedle.
13 . The method of claim 4 , wherein the method comprises administering two different inks to two different areas, wherein the two different inks have different optical properties.
14 . The method of claim 4 , wherein the method comprises selectively administering inks with different optical properties to different areas, thereby generating images with varying optical properties across the different areas.
15 .- 22 . (canceled)
23 . A method of generating a silk photoclick volumetric image within a volume of an article, the method comprising the following steps: a) administering a silk photoclick article ink to a volume, the silk photoclick article ink comprising modified silk nanoparticles and photoclick chromophores, the modified silk nanoparticles comprising modified silk fibroin functionalized with a plurality of first photoclick chemistry pair moieties, wherein the modified silk nanoparticles are biocompatible and bioresorbable, the photoclick chromophores comprising a second photoclick chemistry pair moiety; b) exposing the silk photoclick article ink within the volume to light having a predetermined wavelength for a predetermined exposure length and a predetermined exposure intensity, thereby initiating a known photoreaction and covalently bonding at least a portion of the photoclick chromophores to at least a portion of the modified silk nanoparticles, the administering and exposing of steps a) and b) thereby generating the silk photoclick volumetric image within the volume of the article.
24 .- 30 . (canceled)
31 . The method of claim 4 , wherein the modified silk nanoparticles have an average particle diameter of between 0.1 and 50 micrometers.
32 . The method of claim 4 , wherein the modified silk nanoparticles have an average volumetric density of the plurality of first photoclick chemistry pair moieties of 10-15%.
33 . The method of claim 4 , wherein the plurality of first photoclick chemistry pair moieties comprises, consists essentially of, or consists of methacrylate moieties and the second photoclick chemistry pair moiety is a diaryl-tetrazole moiety.

Description

CLAIM TO PRIORITY This application claims benefit of and is a continuation of International Patent Application No. PCT/US2024/019428 (Attorney Docket. No. 2095.0596), filed Mar. 11, 2024, and entitled “PHOTOCLICK CHEMISTRY OF SILK FOR TEMPORARY UV TATTOOS,” International Pub. No. WO 2024/187194, which is hereby incorporated by reference in its entirety for all purposes. International Patent Application No. PCT/US2024/019428 relates to, incorporates by reference for all purposes, and claims priority to U.S. Application Ser. No. 63/489,366, filed Mar. 9, 2023. STATEMENT REGARDING FEDERALLY FUNDED RESEARCH Not applicable. SEQUENCE LISTING Not applicable. BACKGROUND In the medical field there is a need for a transient, selectively visible tattoo, such as for use as a fiducial marker in teletherapy treatments. Teletherapy treatments are highly localized treatments of radiation that are often used for treatment of certain forms of cancer. Because of the localized nature of the treatment, the radiation beam needs to be precisely aligned with the tumor in order for the treatment to be effective and to minimize side effects. This is often done by performing detailed medical imaging such as CAT, PET or MRI scans of the patient, and placing one or more small tattoos on the skin in the ideal place to align the beam. This must be done as the imaging and treatment often cannot be performed simultaneously. Currently, small permanent marks must be made in the patient's skin. These may be embarrassing to the patient, especially if they are on highly visible portions of the body. Additionally, tattoos can often be painful to apply using traditional methods, and require substantial training and practice to apply reliably. Some fluorescent tattoo inks already exist, but these have at least two principal failings that this invention addresses. First, they are “permanent” tattoos in that they do not have programmable functional lifetimes. These particles degrade stochastically and slowly, so while the tattoo will lose its definition and luster, it will always be somewhat visible for the wearer's lifetime. Secondly, they do not have the ability to switch on their fluorescence post-injection, meaning they are not compatible with the ‘painless’ tattooing process described later in this disclosure. Thus, there is a need for a transient, selectively visible tattoo that can alleviate both problems. When high-value items need to maintain authenticity after exchange through non-secure chains of custody it is common to include anticounterfeiting marks to prevent the items from being replaced by inferior duplicates. Historically anticounterfeiting marks have been created by processes that are very difficult or expensive to replicate (holographic images, fluorescent markings, watermarks, micro printing, etc.) however advances in technology have made these easier to reproduce and thus less secure. Physically unclonable functions (PUFs) are a relatively new form of anti-counterfeiting mark that utilize inherent degrees of randomness to make a mark that is both easy to initially produce and very difficult to replicate. This marking is then stored in a database and the marking on the item can be checked against this registry by individuals throughout the chain of custody to ensure that it has not been replaced by a counterfeit item. A need exists for compositions and methods that overcome one or more of the aforementioned shortcomings. SUMMARY In some aspects, the disclosure herein relates to a silk photoclick tattoo ink including: modified silk nanoparticles including modified silk fibroin functionalized with a plurality of first photoclick chemistry pair moieties, wherein the modified silk nanoparticles are biocompatible and bioresorbable; and photoclick chromophores including a second photoclick chemistry pair moiety, wherein the first photoclick chemistry pair moiety and the second photoclick chemistry pair moiety undergo a known photoreaction when illuminated with light having a predetermined wavelength for a predetermined exposure length and a predetermined exposure intensity, thereby covalently bonding at least a portion of the photoclick chromophores to at least a portion of the modified silk nanoparticles, wherein the silk photoclick tattoo ink is safe for human use as a tattoo ink. In some aspects, the disclosure herein relates to a silk photoclick article ink including: modified silk nanoparticles including modified silk fibroin functionalized with a plurality of first photoclick chemistry pair moieties, wherein the modified silk nanoparticles are biocompatible and bioresorbable; and photoclick chromophores including a second photoclick chemistry pair moiety, wherein the first photoclick chemistry pair moiety and the second photoclick chemistry pair moiety undergo a known photoreaction when illuminated with light having a predetermined wavelength for a predetermined exposure length and a predetermined exposure intensity, thereby cov