Shanyi Lin, Hao Liu, Lei Lv, Guan-Yu Jin, Xinyu Xiang, Bingzheng Yu, Yangang Su, Shiyu Zhang, Zijuan Wang, Zhaofan Yang, Luyao Wang, Li Liu, Shixian Lv, Wei Guo, Canqing Yu
generation from endogenous hydrogen peroxide while depleting intracellular GSH, thereby amplifying ROS production during SDT. Concurrently, SIS3 reprograms CAFs by blocking TGF-β/SMAD3 signaling, reducing collagen deposition and promoting immune cell infiltration. In an osteosarcoma mouse model, the combination of PMH-mediated SDT with SIS3-induced CAF reprogramming reduced collagen deposition by approximately 50 % and triggered robust antitumor immune responses, which collectively contributed to a 76 % inhibition of tumor growth. Collectively, this study demonstrates a novel CAF-targeted SDT strategy integrating ECM remodeling, ROS enhancement, and localized delivery, offering a promising therapeutic paradigm for solid tumor treatment.