Tetrahedral Framework Nucleic Acid Loaded Celastrol Ameliorates Skin Fibrosis by Epithelial-Mesenchymal Transition Prevention

• • TCC (tFNA-Cel complex) significantly inhibited EMT progression in TGF-β-induced HaCaT cells (5 ng mL−1, 24 h), reducing α-SMA and increasing E-cadherin, outperforming Cel or tFNA alone. • • TCC modulated SMAD2 signaling and collagen I expression, demonstrating superior anti-fibrotic efficacy compared to monotherapies. • • TCC reduced NF-κB p65, Bax, and ROS levels, indicating synergistic anti-inflammatory and anti-apoptotic effects. • • The study establishes TCC as a promising nanotherapeutic for skin fibrosis, addressing the limitations of poor bioavailability and narrow therapeutic window of Cel.