A Transdermal Drug Delivery System Based on Nucleic Acid Nanomaterials for Skin Photodamage Treatment

Abstract Skin photodamage, which is induced by ultraviolet (UV) radiation, is a prevalent cause of skin damage. In this study, a transdermal drug delivery system is developed for the topical treatment of skin photodamage, which is composed of tetrahedral framework nucleic acids (tFNAs) and lipoic acid (LA). The tFNAs‐LA (TLA) nanocomposite exhibits excellent biocompatibility, as well as antioxidant, anti‐apoptotic, and anti‐inflammatory capabilities. tFNA, as a carrier, facilitates TLA for cell entry and skin penetration, while the loaded LA enhances the antioxidant and anti‐inflammatory capabilities. In photodamaged human dermal fibroblast (HDF), TLA promotes proliferation and migration while inhibiting apoptosis activation and reactive oxygen species production. Moreover, TLA modulates apoptosis‐related proteins and NF‐κB signaling pathways, increasing cellular secretion while suppressing inflammatory responses in photodamaged HDF cells. In the in vivo experiment, topical application of TLA promotes tissue healing in photodamaged skin, and regulates the expression of inflammation and collagen‐related proteins. It is suggested that the transdermal ability of TLA enables non‐invasive therapy for skin photodamage, highlighting the potential of employing nucleic acid‐based transdermal drug delivery systems for skin disease.