Journal
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
Volume 161, Issue -, Pages 244-252Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.jphotobiol.2016.05.011
Keywords
Photodynamic therapy; Photosensitizer delivery; meta-tetra(hydroxyphenyl)chlorine; Liposomes; Multicellular tumor spheroids
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Funding
- University of Padova
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In cancer photodynamic therapy (PDT), an efficient and homogeneous intratumoral accumulation of the photo-sensitizer (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 (R)) and in its non PEGylated and PEGylated liposomal formulations, Foslip (R) and Fospeg (R), 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 (R) and Fospeg (R) with respect to Foscan (R). Irradiation with red light, following 24 h 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 (R). (C) 2016 Elsevier B.V. All rights reserved.
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