H2S-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.