Effects of zinc porphyrin and zinc phthalocyanine derivatives in photodynamic anticancer therapy under different partial pressures of oxygen in vitro

Invest New Drugs. 2021 Feb;39(1):89-97. doi: 10.1007/s10637-020-00990-7. Epub 2020 Aug 24.

Abstract

Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS2) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS4). Fluorescence microscopy revealed their different localizations within the cells. ZnTPPS4 seems to be mostly limited to the cytosol and lysosomes, whereas ZnPcS2 is most likely predominantly attached to membrane structures, including plasmalemma and the mitochondrial membrane. Phototoxicity assays of PDT-treated cells carried out under different partial pressures of oxygen showed dose-dependent responses. Interestingly, ZnPcS2 was also photodynamically effective at a minimal level of oxygen, under a nitrogen atmosphere. On the other hand, hyperbaric oxygenation did not lead to a higher PDT efficiency of either photosensitizer. Although both photosensitizers can induce a significant drop in mitochondrial membrane potential, ZnPcS2 has a markedly higher effect on mitochondrial respiration that was completely blocked after two short light cycles. In conclusion, our observations suggest that PDT can be effective even in hypoxic conditions if a suitable sensitizer is chosen, such as ZnPcS2, which can inhibit mitochondrial respiration.

Keywords: Hyperbaria; Photodynamic therapy; Photosensitizers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Metalloporphyrins / administration & dosage
  • Metalloporphyrins / pharmacology*
  • Mitochondria / drug effects
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / pharmacology*
  • Oxygen / administration & dosage
  • Oxygen / pharmacology*
  • Partial Pressure
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacology
  • Singlet Oxygen / analysis

Substances

  • Indoles
  • Metalloporphyrins
  • Organometallic Compounds
  • Photosensitizing Agents
  • Singlet Oxygen
  • zinc tetraphenylporphyrin
  • zinc phthalocyanine disulfonate
  • Oxygen