An Activatable\nHeavy-Atom-Free Upconversion Photosensitizer\nfor Targeted Imaging and Treatment of Tumors

Photodynamic\ntherapy (PDT) is an innovative and promising\nmethod\nfor treating tumors that has attracted significant interest but still\nfaces several challenges, such as a lack of selectivity, deep penetration\nof light, and efficient ROS generation. To address these challenges,\nwe optimized and synthesized a series of photosensitizers and successfully\ndeveloped a heavy-atom-free near-infrared FUCL photosensitizer NFh-NMe-2.\nThis photosensitizer can generate singlet oxygen (<sup>1</sup>O<sub>2</sub>) and induce cellular apoptosis under 808 nm light. For the\nsafe ablation of microtumors in vivo, an activatable FUCL photosensitizer\nNFh-NTR was developed based on the overexpression of nitroreductase\n(NTR). NFh-NTR could be activated by NTR, leading to the release of\nthe photosensitizer NFh-NMe-2, restoring the fluorescence signal,\nand effectively killing tumor cells under 808 nm light irradiation.\nThis work opens new possibilities in the chemical design of an FUCL\nphotosensitizer for cancer treatment.