H ₂ S-Activated Theranostic Platform for Precise Photoablation of Colorectal Tumors with NIR-II Dual-Modal Phototherapy

Due to overexpression of hydrogen sulfide (H₂S) in colorectal tumors, the combination of H₂S targeting with traditional phototherapy is expected to achieve precision treatment of colorectal tumors and reduce side effects while enhancing therapeutic efficacy. In this study, we developed a theranostic nanoplatform (N-BOD-P-T) of H₂S-activated dual-modal phototherapy for precise photoablation of colorectal tumors utilizing photodynamic therapy (PDT) and photothermal therapy (PTT) guided by H₂S-activated NIR-II imaging. N-BOD-P-T could selectively accumulate at H₂S-overexpressed colorectal tumors with a fluorescence conversion from NIR-I to NIR-II. Subsequent dual-modal phototherapy would exert synergistic effects through the following mechanisms: 1. PDT-generated reactive oxygen species could inhibit the expression of heat shock proteins to reduce tumor thermotolerance caused by PTT; 2. PTT enhanced tumor blood flow and oxygen supply, thereby addressing oxygen consumption in PDT. Collectively, this H₂S-activated NIR-II dual-modal phototherapy nanoplatform represents a promising theranostic tool for the precision treatment of colorectal cancer.