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.
Shudan Yang  1 ,  Lushun Wang  1 ,  Axel Loredo  1 ,  Shichao Wang  1 ,  Nischal Ada  1 ,  Han Xiao  2
Affiliations
  • 1. Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, United States.
  • 2. Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, United States; Department of Biosciences, Rice University, 6100 Main Street, Houston, TX 77005, United States; Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, United States. Electronic address: [email protected].
PMID: 37290494 DOI: 10.1016/j.bmcl.2023.129365
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.