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. Epub 2024 Dec 5.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Nitroreductases / metabolism
  • Photochemotherapy*
  • Photosensitizing Agents* / chemical synthesis
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Photosensitizing Agents* / therapeutic use
  • Singlet Oxygen / metabolism

Substances

  • Photosensitizing Agents
  • Singlet Oxygen
  • Nitroreductases
  • Antineoplastic Agents