Singlet oxygen-activatable Paclitaxel prodrugs via intermolecular activation for combined PDT and chemotherapy

Bioorg Med Chem Lett. 2019 Jun 15;29(12):1537-1540. doi: 10.1016/j.bmcl.2019.03.053. Epub 2019 Apr 2.

Abstract

Systemic side effects and high hydrophobicity are major disadvantages of paclitaxel (PTX), one of the most popular anticancer drugs. Here, we present singlet oxygen (SO)-activatable and mitochondria-targeted PTX prodrugs to overcome these problems and boost the cytotoxic effect of photodynamic therapy (PDT). Three PTX prodrugs were prepared by conjugating PTX with various cationic groups. Hydrophobicity was determined in LogD7.4 value. Mitochondrial localization was confirmed by fluorescence confocal microscopy and uptake of mitochondria-specific fluorescence probe. Dark- and photo-toxicity were measured in AY-27 cells with MTT assay. All three prodrugs showed better hydrophilicity than PTX and improved phototoxicity when combined with protoporphyrin IX (PpIX) PDT. In conclusion, SO-activatable and higher hydrophilic PTX prodrugs were successfully prepared. This approach could be used to improve the antitumor efficacy of PDT without the systemic side effects of PTX.

Keywords: Paclitaxel; Photo-unclick; Photodynamic therapy; Singlet oxygen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Humans
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use*
  • Photochemotherapy / methods*
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use*
  • Singlet Oxygen

Substances

  • Antineoplastic Agents, Phytogenic
  • Prodrugs
  • Singlet Oxygen
  • Paclitaxel