Intracellular re-localisation by photochemical internalisation enhances the cytotoxic effect of gelonin--quantitative studies in normal rat liver

Journal of Controlled Release : Official Journal of the Controlled Release Society
Josephine H WoodhamsStephen G Bown

Abstract

Photochemical internalisation (PCI) is a delivery technology that employs a sub-lethal form of photodynamic therapy (PDT) in which a photosensitiser is activated by light to break down intracellular membranes and release macromolecules into the cytosol where they can be biologically active. Although PCI does enhance the PDT killing of transplanted tumours in mice after local injection of the cytotoxic agent, gelonin, the redistribution of gelonin from intracellular organelles into the cytosol has only previously been demonstrated in vitro. This study is designed to understand the factors controlling the efficacy of PCI in vivo and to document the mechanism of action. Using the photosensitiser AlS(2)Pc in studies on normal rat liver, we have demonstrated in vivo that gelonin is initially taken up into lysosomes, but can be released into the cytosol using PCI. Furthermore, PCI enhances the PDT effect after systemic administration of gelonin (volume of necrosis increased x2.5 when gelonin is given one hour before light), with the remarkably low dose of 5 microg/kg (10,000 times lower than the LD50); in the absence of light, there is no effect with 500 microg/kg. These results suggest that PCI may have a useful role to play in the ...Continue Reading

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Citations

Mar 12, 2015·International Journal of Cancer. Journal International Du Cancer·Alejandra Martinez de Pinillos BayonaJosephine H Woodhams
Jun 22, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hsueh-Lin LuPing-Shan Lai
Mar 12, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Monica BostadPål Kristian Selbo
Sep 6, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Julie T-W WangAlexander J MacRobert
Mar 11, 2016·Physics in Medicine and Biology·Brian W PogueTayyaba Hasan
Oct 24, 2018·Journal of Biomedical Optics·Brian W Pogue, Brian C Wilson

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