Topical treatment for abnormal scars using spherical nucleic acids

Abnormal scarring, manifesting as hypertrophic or keloid scars, affects millions of people every year after surgeries, injury, and even as residual from skin disease. These overgrown scars can be painful, itchy, and often disfiguring. Although many treatments for abnormal scars exist, they are often invasive and do not prevent scar recurrence. Spherical nucleic acids (SNAs) are nanoparticle-oligonucleotide conjugates consisting of a nanoparticle core and dense shell of oriented oligonucleotides. In this work, we exploited the ability of SNAs to penetrate skin and their potency for gene regulation to develop a topically-applied and self-administrable abnormal scar treatment. Three SNA constructs-gold nanoparticle conjugate SNAs, liposomal SNAs, and micellular SNAs-were designed to target the production of transforming growth factor beta 1 (TGFβ1), the overexpression of which has been linked to abnormal scar formation. These SNA constructs were able to significantly reduce the expression level of TGFβ1 in both scar-derived and normal fibroblasts in vitro (p < 0.05). Additionally, all SNA constructs were able to significantly reduce both TGFβ1 expression and scar elevation in a rabbit ear model of abnormal scarring (p < 0.05). This work opens up the potential for SNAs to be used in treating fibroproliferative disorders, and expands their scope as topical gene regulation therapeutics. This study also offers a new possibility for effective, non-invasive abnormal scar management strategies.