Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy

Bioorg Med Chem. 2018 Jan 1;26(1):107-118. doi: 10.1016/j.bmc.2017.11.024. Epub 2017 Nov 15.

Abstract

The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency.

Keywords: Cancer; Photodynamic therapy; Two-photon absorption; Vinyltriphenylamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Cations / chemical synthesis
  • Cations / chemistry
  • Cations / pharmacology
  • Cell Death / drug effects
  • Dose-Response Relationship, Drug
  • HT29 Cells
  • Humans
  • Mitochondria / drug effects*
  • Molecular Structure
  • Photochemotherapy*
  • Photons*
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Aniline Compounds
  • Cations
  • Photosensitizing Agents
  • Porphyrins