Photodynamic Therapy Using Photosensitizer-encapsulated Polymeric Nanoparticle to Overcome ATP-Binding Cassette Transporter Subfamily G2 Function in Pancreatic Cancer
Menée sur deux lignées cellulaires de cancer du pancréas et à l'aide de xénogreffes sur des modèles murins, cette étude analyse l'intérêt d'utiliser, dans le cadre d'une photothérapie dynamique, des nanoparticules pour améliorer le transport des photosensibilisants dans les cellules cancéreuses surexprimant les protéines transmembranaires ABCG2
Chlorin-based photosensitizers are commonly used in photodynamic therapy (PDT). These drugs are effluxed by cell-membrane transporters, such as the ATP-binding cassette subfamily G member 2 (ABCG2). PDT efficacy is limited in tumor cells expressing high levels of these proteins. Pancreatic cancer cell lines AsPC-1 and MIA PaCa-2, which have high and low ABCG2 expression, respectively, were used and ABCG2-overexpressing MIA PaCa-2 cells were generated. We compared PDT efficacy between Chlorin e6 (Ce6) and cationic photosensitizer-encapsulated polymeric nanoparticle (PS-pNP) which is comprised with Ce6, polyethylene glycol and polyethylenimine. The intracellular concentration of Ce6 was significantly higher in MIA PaCa-2 cells than in AsPC-1 or ABCG2-overexpressing MIA PaCa-2 cells. PS-pNP increased intracellular levels of the photosensitizer in all cell lines. The cell viability experiments indicated increased Ce6 resistance in ABCG2-overexpressing cells. In contrast, PS-pNP produced similar levels of cytotoxicity in each of the cancer cell lines tested. Singlet oxygen production was higher in cells treated with PS- pNP than in those treated with Ce6. Furthermore, in heterotopic and orthotopic AsPC-1-xenograft mouse models, PDT using PS-pNP significantly reduced tumor volume in comparison to that of Ce6 treatment. PS-pNP could increase intracellular Ce6 concentration, which were related with reduced ABCG2-mediated efflux of Ce6, thereby enhancing the effects of PDT in pancreatic cancer cells.
http://mct.aacrjournals.org/content/early/2017/04/15/1535-7163.MCT-16-0642.abstract