Tetrahedral Framework Nucleic Acids Inhibit Skin Fibrosis via the Pyroptosis Pathway

Abstract

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.

Pyroptosis and inflammasomes in diabetic wound healing

“…Both NLRP3 inflammasome and pro-caspase-1 levels were downregulated after TFNA treatment, indicating that the inflammasome was reduced and the active form of caspase-1 was reduced, resulting in a subsequent down-regulation of Nterminal GSDMD levels. The results showed that TFNA has anti-inflammatory and anti-fibrotic abilities without cytotoxicity (74). In this study, proteins related to pyroptosis and inflammasome signaling pathways were detected, including pro-caspase-1, caspase-1, NLRP3, GSDMD, etc.…”

Albumin-Coated Framework Nucleic Acids as Bionic Delivery System for Triple-Negative Breast Cancer Therapy

“…Respectively, every group (250 nM tFNA) was incubated with MDA-MB-231, MCF-7 for 24, 48, and 72 h. The medium was replaced with media containing 10% CCK-8 and then incubated in the dark for more than 2 h. The absorbance at a wavelength of 450 nm was measured. 32 2.12. Cell Apoptosis Assay.…”

“…The blot signals were observed by an enhanced chemiluminescence detection system (Bio-Rad). 32,36 2.14. In Vivo Therapy.…”

Self-Assembled Immunostimulatory Tetrahedral Framework Nucleic Acid Vehicles for Tumor Chemo-immunotherapy

“…Remarkably, as a kind of framework nucleic acid synthesized from oligonucleotides by Watson−Crick pairing, tFNA, exhibited great potential in drug delivery for its outstanding intrinsic biocompatibility 8 superior membrane permeability. 9−11 Its extensive biological application in drug or gene-targeted delivery 12 and diagnosis has 13,14 has been widely reported. 10,15 As a result, the application of tFNA in passive tumor-targeted delivery via EPR was promising because of its special framework morphology and desirable size.…”

“…This phenomenon is known as the enhanced permeability and retention (EPR) effect. , Although the development of drug-loaded nanoparticles has been evolving for decades, they have not yet been widely approved for clinical use due to biosafety concerns. Remarkably, as a kind of framework nucleic acid synthesized from oligonucleotides by Watson–Crick pairing, tFNA, exhibited great potential in drug delivery for its outstanding intrinsic biocompatibility and superior membrane permeability. − Its extensive biological application in drug or gene-targeted delivery and diagnosis has , has been widely reported. , As a result, the application of tFNA in passive tumor-targeted delivery via EPR was promising because of its special framework morphology and desirable size. − …”