Uptake and photo-toxicity of Foscan®, Foslip® and Fospeg® in multicellular tumor spheroids.
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®.
Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35121 Padova, Italy. Electronic address: elisa.gaio@studenti.unipd.it.
Elisa
E
Gaio
Biolitec Research GmbH, Otto-Schott-Strasse 15, 07745 Jena, Germany. Electronic address: Dietrich.Scheglmann@biolitec.com.
Dietrich
D
Scheglmann
Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35121 Padova, Italy. Electronic address: elena.reddi@unipd.it.
Elena
E
Reddi
Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35121 Padova, Italy. Electronic address: francesca.moret@unipd.it.
Francesca
F
Moret
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004339:Drug Compounding; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008652:Mesoporphyrins / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; C072269:temoporfin
Liposomes; Multicellular tumor spheroids; Photodynamic therapy; Photosensitizer delivery; meta-tetra(hydroxyphenyl)chlorine