Cross-Linked Fluorescent Supramolecular Nanoparticles as Finite Tattoo Pigments with Controllable Intradermal Retention Times

Abstract

Tattooing has been utilized by the medical community for precisely demarcating anatomic landmarks. This practice is especially important for identifying biopsy sites of nonmelanoma skin cancer (NMSC) due to the long interval (i.e., up to 3 months) between the initial diagnostic biopsy and surgical treatment. Commercially available tattoo pigments possess several issues, which include causing poor cosmesis, being mistaken for a melanocytic lesion, requiring additional removal procedures when no longer desired, and potentially inducing inflammatory responses. The ideal tattoo pigment for labeling of skin biopsy sites for NMSC requires (i) invisibility under ambient light, (ii) fluorescence under a selective light source, (iii) a finite intradermal retention time (ca. 3 months), and (iv) biocompatibility. Herein, we introduce cross-linked fluorescent supra-molecular nanoparticles (c-FSNPs) as a “finite tattoo” pigment, with optimized photophysical properties and intradermal retention time to achieve successful in vivo finite tattooing. Fluorescent supramolecular nanoparticles encapsulate a fluorescent conjugated polymer, poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene] (MPS-PPV), into a core via a supramolecular synthetic approach. FSNPs which possess fluorescent properties superior to those of the free MPS-PPV are obtained through a combinatorial screening process. Covalent cross-linking of FSNPs results in micrometer-sized c-FSNPs, which exhibit a size-dependent intradermal retention. The 1456 nm sized c-FSNPs display an ideal intradermal retention time (ca. 3 months) for NMSC lesion labeling, as observed in an in vivo tattoo study. In addition, the c-FSNPs induce undetectable inflammatory responses after tattooing. We believe that the c-FSNPs can serve as a “finite tattoo” pigment to label potential malignant NMSC lesions.

Dual Supramolecular Nanoparticle Vectors Enable CRISPR/Cas9‐Mediated Knockin of Retinoschisin 1 Gene—A Potential Nonviral Therapeutic Solution for X‐Linked Juvenile Retinoschisis

“…The multivalent Ad/CD molecular recognition allows modular control over the sizes, surface chemistry, and payloads of SMNP vectors, promising a diversity of imaging [ 18,19 ] and therapeutic applications. [ 20 ] We have shown that this self‐assembly strategy can be utilized for combinatorial formulation and screening of SMNPs to optimize formulations with significantly improved delivery performance. [ 21 ]…”

“…Our self‐assembly strategy [ 18 ] enables precise control over two synthetic variables—(i) Ad‐PAMAM/CD‐PEI ratios, and (ii) the coverage of a membrane penetration ligand, TAT. [ 20c ] Through small‐scale combinatorial screenings, optimal performances were identified for the formulations of Cas9/sgRNA‐plasmid⊂SMNPs and Donor‐RS1/GFP‐plasmid⊂SMNPs according to their performances for inducing CRISPR/Cas9‐mediated insertion and deletion events (indels) and GFP transfection, respectively. The two optimized SMNP vectors were then employed to achieve CRISPR/Cas9‐mediated knockin of RS1/GFP gene in growth‐synchronized B16 cells.…”

Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications

“…Tseng and co‐workers constructed a micrometer‐sized fluorescent supramolecular material as finite tattoo pigments, encapsulating a fluorescent conjugated polymer using the supramolecular approach and displaying the size‐dependent intradermal time. [ 104 ] Typically, Liu and co‐workers developed novel fluorescent supramolecular nanoparticles, consisting of β‐CD‐modified hyaluronic acid and TPE‐modified adamantane. [ 105 ] This supramolecular assembly exhibited enhanced fluorescent emission owing to the TPE cores condensed by host–guest interaction, which could be used for targeted‐imaging of cancer cells.…”

Supramolecular Nanosubstrate‐Mediated Delivery for CRISPR/Cas9 Gene Disruption and Deletion

“…Previously, we reported a flexible self‐assembled approach for preparing supramolecular nanoparticle (SMNP) vectors [ 22 ] via mixing three common molecular building blocks, that is, adamantane‐grafted polyamidoamine dendrimer (Ad‐PAMAM), adamantane‐grafted poly(ethylene glycol) (Ad‐PEG), and β‐cyclodextrin‐grafted polyethyleneimine (CD‐PEI). By leveraging multivalent molecular interactions between β‐cyclodextrin (CD) and adamantane (Ad) motifs, modular control over the surface chemistry, sizes, and payloads of the nanoparticles can be easily achieved, offering a versatile playground for various diagnostic imaging [ 23 ] and therapeutic applications. [ 24 ] Inspired by existing substrate‐mediated delivery approaches, [ 25 ] we developed a supramolecular nanosubstrate‐mediated delivery (SNMD) strategy [ 26 ] to improve the delivery efficiency of SMNP vectors, where Ad‐grafted silicon nanowire substrates (Ad‐SiNWS) were designed for dynamic assembly and local enrichment of SMNPs.…”

“…By leveraging multivalent molecular interactions between β‐cyclodextrin (CD) and adamantane (Ad) motifs, modular control over the surface chemistry, sizes, and payloads of the nanoparticles can be easily achieved, offering a versatile playground for various diagnostic imaging [ 23 ] and therapeutic applications. [ 24 ] Inspired by existing substrate‐mediated delivery approaches, [ 25 ] we developed a supramolecular nanosubstrate‐mediated delivery (SNMD) strategy [ 26 ] to improve the delivery efficiency of SMNP vectors, where Ad‐grafted silicon nanowire substrates (Ad‐SiNWS) were designed for dynamic assembly and local enrichment of SMNPs. As cells settle onto the substrates, their membranes form intimate contacts with the nanowires and generate transient defects that facilitate intracellular uptake of SMNPs.…”