Visible light-activated prodrug system with a novel heavy-atom-free photosensitizer

Bioorg Med Chem Lett. 2023 Jul 15:91:129365. doi: 10.1016/j.bmcl.2023.129365. Epub 2023 Jun 7.

Abstract

The use of light to activate prodrugs offers a promising method for the precise control of drug release, reducing drug-related side effects, and enhancing therapeutic effectiveness. We have created a novel prodrug system that utilizes a unique, heavy-atom-free photosensitizer to produce singlet oxygen, which then triggers the conversion of the prodrug into its active form. This system has been successfully demonstrated through the creation of "photo-unclick" prodrugs of paclitaxel (PTX), combretastatin A-4 (CA-4), and 10-hydroxy-7-ethylcamptothecin (SN-38). These prodrugs show decreased toxicity in the absence of light, but exhibit increased toxicity when exposed to red light.

Keywords: Anticancer; Heavy-atom free; Photo-cleavage; Photosensitizer; Prodrugs; Visible light.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Light
  • Paclitaxel / pharmacology
  • Photosensitizing Agents* / pharmacology
  • Prodrugs* / pharmacology
  • Singlet Oxygen

Substances

  • Paclitaxel
  • Photosensitizing Agents
  • Prodrugs
  • Singlet Oxygen
  • fosbretabulin