Tetrahedral Framework Nucleic Acids Inhibit Skin Fibrosis via the Pyroptosis Pathway

The skin is the first line of defense for the human body and is vulnerable to injury. Various topical or systemic diseases facilitate skin inflammation, and when the intensity or duration of skin injury exceeds the ability of tissue repair, fibrosis, an outcome of a dysregulated tissue-repair response, begins to dominate the repair process. However, existing methods for reducing skin fibrosis are insufficient and cause side effects, highlighting the need for drugs that effectively inhibit skin fibrosis and reduce immunogenicity, inflammation, apoptosis, and pyroptosis. Tetrahedral framework nucleic acids (tFNAs) are DNA nanomaterials that have a unique spatial structure, demonstrate excellent biosecurity, and promote anti-inflammatory, antioxidative, antifibrotic, angiogenic, and skin-wound-healing activities with almost no toxicity. Here, we explored the potential of tFNAs in skin fibrosis therapy in vitro and in vivo. After incubating cells or injecting mice with profibrogenic molecules and tFNAs, we found that the tFNAs inhibited the epithelial–mesenchymal transition, reduced inflammatory factor levels, decreased skin collagen content, and inhibited the pyroptosis pathway. These findings suggest the potential of tFNAs in treating pyroptosis-related diseases.