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

  • J Med Chem. 2024 Dec 26;67(24):22322-22331. doi: 10.1021/acs.jmedchem.4c02679.
Chao Zhao  1 ,  Wanlu Sun  1 ,  Yanyan Zhu  1 ,  Xiaoyan Huang  1 ,  Ye Sun  1 ,  Hai-Yan Wang  2 ,  Yi Pan  3 ,  Yi Liu  1
Affiliations
  • 1. School of Engineering, China Pharmaceutical University, Nanjing 211198, China.
  • 2. School of Mechanical Engineering, Southeast University, Nanjing 211189, China.
  • 3. School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
PMID: 39635996 DOI: 10.1021/acs.jmedchem.4c02679
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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