Epidermal SR-A Complexes Are Lipid Raft Based and Promote Nucleic Acid Nanoparticle Uptake.

Scavenger receptors clear pathogens, transport lipid, and mediate polyanionic ligand uptake in macrophages, but their expression and role in the skin are poorly understood. Although the epidermal barrier typically excludes nucleic acid entry, topically applied, spherically arranged oligonucleotide nanoconjugates (spherical nucleic acids [SNAs]) penetrate mouse skin, three-dimensional (3D) skin equivalents, and human skin. We explored the mechanism of SNA uptake in normal human epidermal keratinocytes and 3D skin equivalents. Normal human epidermal keratinocytes and 3D raft treatment with SR-A inhibitors reduced SNA uptake by >80%. The human epidermis expresses SR-As SCARA3 and, to a lesser extent, MARCO. Simultaneous lentiviral knockdown of SCARA3 and MARCO reduced SNA uptake in normal human epidermal keratinocytes and 3D rafts after topical application, affirming a role for SR-As in SNA uptake and 3D raft penetration. Incubation of normal human epidermal keratinocytes at 4oC or with sodium azide prevented SNA uptake, suggesting active endocytosis. Endocytosis inhibitors, immunofluorescence, immunoprecipitation, and knockdown studies localized functional SR-As to FLOT-1-containing lipid rafts throughout the epidermis and CAV-1-containing rafts only in the upper epidermis. These studies suggest a central role for SR-A complexes in epidermal lipid rafts in mediating the uptake of nucleic acid‒laden nanoparticles.

Attenuation of Abnormal Scarring Using Spherical Nucleic Acids Targeting Transforming Growth Factor Beta 1.

Abnormal scarring is a consequence of dysregulation in the wound healing process, with limited options for effective and noninvasive therapies. Given the ability of spherical nucleic acids (SNAs) to penetrate skin and regulate gene expression within, we investigated whether gold-core SNAs (AuSNAs) and liposome-core SNAs (LSNAs) bearing antisense oligonucleotides targeting transforming growth factor beta 1 (TGF-ß1) can function as a topical therapy for scarring. Importantly, both SNA constructs appreciably downregulated TGF-ß1 protein expression in primary hypertrophic and keloid scar fibroblasts in vitro. In vivo, topically applied AuSNAs and LSNAs downregulated TGF-ß1 protein expression levels and improved scar histology as determined by the scar elevation index. These data underscore the potential of SNAs as a localized, self-manageable treatment for skin-related diseases and disorders that are driven by increased gene expression.

Polymer-based tubular microbots: role of composition and preparation.

The influence of the composition and electropolymerization conditions upon the propulsion of new template-prepared polymer-based bilayer microtubular microbots is described. The effects of different electropolymerized outer layers, including polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT), polyaniline (PANI), and of various inner catalytic metal surfaces (Ag, Pt, Au, Ni-Pt alloy), upon the movement of such bilayer microtubes are evaluated and compared. Electropolymerization conditions, such as the monomer concentration and medium (e.g. surfactant, electrolyte), have a profound effect upon the morphology and locomotion of the resulting microtubes. The most efficient propulsion is observed using PEDOT/Pt microbots that offer a record-breaking speed of over 1400 body lengths s(-1) at physiological temperature, which is the fastest relative speed reported to date for all artificial micro/nanomotors. An inner Pt-Ni alloy surface is shown useful for combining magnetic control and catalytic fuel decomposition within one layer, thus greatly simplifying the preparation of magnetically-guided microbots. Polymer-based microbots with an inner gold layer offer efficient biocatalytic propulsion in low peroxide level in connection to an immobilized catalase enzyme. Metallic Au/Pt bilayer microbots can also be prepared electrochemically to offer high speed propulsion towards potential biomedical applications through functionalization of the outer gold surface. Such rational template preparation and systematic optimization of highly efficient microbots hold considerable promise for diverse practical applications.