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Journal of Medicinal Chemistry

Journal of Medicinal Chemistry

IF: 6.79
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An Activatable Heavy-Atom-Free Upconversion Photosensitizer for Targeted Imaging and Treatment of Tumors

Published:5 December 2024 DOI: 10.1021/acs.jmedchem.4c02679
Chao Zhao, Wanlu Sun, Yanyan Zhu, Xiaoyan Huang, Ye Sun, Hai-Yan Wang, Yi Pan, Yi Liu

Abstract

Photodynamic therapy (PDT) is an innovative and promising method for treating tumors that has attracted significant interest but still faces several challenges, such as a lack of selectivity, deep penetration of light, and efficient ROS generation. To address these challenges, we optimized and synthesized a series of photosensitizers and successfully developed a heavy-atom-free near-infrared FUCL photosensitizer NFh-NMe-2. This photosensitizer can generate singlet oxygen (1O2) and induce cellular apoptosis under 808 nm light. For the safe ablation of microtumors in vivo, an activatable FUCL photosensitizer NFh-NTR was developed based on the overexpression of nitroreductase (NTR). NFh-NTR could be activated by NTR, leading to the release of the photosensitizer NFh-NMe-2, restoring the fluorescence signal, and effectively killing tumor cells under 808 nm light irradiation. This work opens new possibilities in the chemical design of an FUCL photosensitizer for cancer treatment.

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