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We developed a multifunctional nucleic acid nanomedicine, Apt02\u2013tFNAs\u2013siTGF\u2010\u03b2 (A\u2010T\u2010S), in which tetrahedral framework nucleic acids co\u2010deliver siRNA against TGF\u2010\u03b2 (siTGF\u2010\u03b2) and the proangiogenic aptamer Apt02, enabling programmable integration and stable delivery. A\u2010T\u2010S was efficiently internalized by macrophages, human oral mucosal fibroblasts, and endothelial cells and concurrently modulated inflammatory phenotypes, fibrotic programs, and angiogenesis\u2010related features in vitro. Transcriptomic profiling revealed coordinated reprogramming of pathways involved in inflammation, fibrosis, and extracellular matrix remodeling. In a rat OSF model, A\u2010T\u2010S reduced collagen deposition and profibrotic signaling while mitigating inflammatory infiltration and vascular abnormalities, without evident toxicity in major organs. These findings indicate that A\u2010T\u2010S can synergistically remodel the OSF lesion microenvironment and represents a promising strategy for OSF and other fibroinflammatory diseases.<\/jats:p>","DOI":"10.1002\/smll.74277","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:01:47Z","timestamp":1781859707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Multifunctional Nucleic Acid Nanomedicine Coregulates Angiogenesis and Fibrosis to Treat Oral Submucous Fibrosis"],"prefix":"10.1002","volume":"22","author":[{"given":"Xiao","family":"Fu","sequence":"first","affiliation":[{"name":"Hainan General Hospital Hainan Affiliated Hospital of Hainan Medical University  Haikou Hainan 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