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Vascular endothelial cells as targets for photochemical internalization ( PCI )
Author(s) -
Vikdal Marie,
Weyergang Anette,
Selbo Pål Kristian,
Berg Kristian
Publication year - 2013
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12126
Subject(s) - ht1080 , saporin , cancer research , conventional pci , fibrosarcoma , endothelial stem cell , cytotoxic t cell , cancer cell , chemistry , medicine , cytotoxicity , microbiology and biotechnology , immunology , biology , immunotoxin , biochemistry , pathology , cancer , in vitro , myocardial infarction
Cancer treatment can be exerted by targeting both cancer cells and the vasculature supplying solid tumors. Photochemical internalization ( PCI ) is a modality for cytosolic drug delivery, but recent data on contrast‐enhanced MRI have indicated that the method also reduces blood perfusion in HT 1080 fibrosarcoma xenografts. The present report aims to investigate if PCI may exert direct cytotoxic effects on endothelial cells. PCI of saporin was performed on endothelial human umbilical vein endothelial cell ( HUVEC ) and fibrosarcoma cells ( HT 1080) using two PCI ‐relevant photosensitizers, TPPS 2a and AlPcS 2a . A 22‐ and 13‐fold higher photosensitizer uptake was detected in the endothelial cells compared with the HT 1080 cells for AlPcS 2a and TPPS 2a, respectively. PCI of saporin was, however, found more effective in HT 1080 cells. For HT 1080 cells, PCI with saporin increased cell killing 1.9‐fold over photodynamic therapy alone, but under the same conditions, only increased HUVEC cell killing by 1.6‐ and 1.3‐fold with AlPcS 2a and TPPS 2a , respectively. Saporin uptake was higher in HUVEC s than in the HT 1080 cells, hence did not reflect the cell line differences in PCI efficacy. This is the first report on PCI ‐mediated kill of endothelial cells and lays the foundation for further preclinical evaluation of the PCI technology as an antivascular strategy to ablate tumors.