Circularization of Aptamer Nanomedicine Improves Nuclease Resistance, Targeted Recognition, and Transdermal Effect for Topical Psoriasis Therapy

Inhibiting excessive hyperproliferation and inflammatory responses of keratinocytes are two primary tasks against psoriasis, which, however, have not been well integrated by the current available nanomedicines. Herein, we develop a nucleic acid nanomedicine through coassembly of circular aptamers and gold nanoclusters via electrostatic interactions for psoriasis therapy. After topical application, this nanomedicine bearing vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) aptamers crosses the stratum corneum and enters the deep layers of psoriatic site, from which it specifically inhibits VEGF-mediated keratinocyte proliferation and TNF-α-mediated inflammatory responses simultaneously. More importantly, the circular aptamers further promote the nuclease resistance, targeted recognition, and transdermal effect of the nanomedicine, as compared to their linear counterparts. These improved synergistic actions effectively prevent and cure psoriasis of mice induced by imiquimod. It is anticipated that this study provides a general strategy for targeted regulation of intricate pathological microenvironments beyond psoriasis.