Uptake and photo-toxicity of Foscan®, Foslip® and Fospeg® in multicellular tumor spheroids

J Photochem Photobiol B. 2016 Aug:161:244-52. doi: 10.1016/j.jphotobiol.2016.05.011. Epub 2016 May 14.

Abstract

In cancer photodynamic therapy (PDT), an efficient and homogeneous intratumoral accumulation of the photosensitizer (PS) is required to induce cell damages in the entire tumor mass after light activation. Thus, in this study we investigated penetration ability and photodynamic efficiency of meta-tetra(hydroxyphenyl)chlorin (m-THPC) in standard formulation (Foscan®) and in its non PEGylated and PEGylated liposomal formulations, Foslip® and Fospeg®, in HeLa multicellular spheroids, as in vitro avascular models of solid tumors. Confocal microscopy studies demonstrated that m-THPC fluorescence was confined in the external cell layers of spheroids with a slightly higher accumulation of Foslip® and Fospeg® with respect to Foscan®. Irradiation with red light, following 24h incubation of spheroids with the m-THPC formulations, caused however photodamages also in cells located in the central part of spheroids, as documented by transmission electron microscopy analyses. Overall, the photodynamic effects of the three m-THPC formulations on HeLa cell spheroids were comparable in terms of cell viability measured with the MTS assay. It is however worth noting that the delivery of m-THPC by liposomes significantly abolished its cytotoxicity in the dark, slightly improved the cellular uptake and, following PDT, promoted cell loss and spheroid disassembling to a higher extent when compared to Foscan®.

Keywords: Liposomes; Multicellular tumor spheroids; Photodynamic therapy; Photosensitizer delivery; meta-tetra(hydroxyphenyl)chlorine.

MeSH terms

  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Drug Compounding
  • Female
  • HeLa Cells
  • Humans
  • Light*
  • Mesoporphyrins / chemistry
  • Mesoporphyrins / therapeutic use
  • Mesoporphyrins / toxicity*
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Photochemotherapy
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / therapeutic use
  • Photosensitizing Agents / toxicity*
  • Polyethylene Glycols / chemistry
  • Spheroids, Cellular / drug effects*
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / radiation effects
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Mesoporphyrins
  • Photosensitizing Agents
  • Polyethylene Glycols
  • temoporfin