Tu1949 Escaping of ATP-Binding Cassette Sub Family G Member 2 by Pegylated-Photosensitizer Increases the Efficacy of Photodynamic Therapy in Pancreatic Cancer

Abstract

Purpose : Porphyrin-based photosensitizers are most commonly used in photodynamic therapy (PDT). However, these drugs are exported extracellularly by a cell-mambrane transporter, the ATP-binding cassette subfamily G member 2 (ABCG2), which decreases the PDTinduced cytotoxicity in cancer treatment. Pegylation of a drug increases its molecular size. We hypothesized that intracellular level of a porphyrin can be increased by its pegylated form, which enhance the PDT-induced cytotoxicity. Our aim of study was to examine the escaping of ABCG2 function in the PDT using pegylated-Chlorin E6 (Che6) in the pancreatic cancer cells. Methods : We pegylated Che6 using a methoxy polyethylene glycol and branched polyethylenimine. AsPC-1 and MiaPaCa-2 cells were selected, which showed the low and high ABCG2 expression level, respectively. Intracellular level of Che6 and pegylatedChe6 was detected by Fluorescence meter, FACS and confocal microscope. Cells were incubated with 0.1 10 μM of Che6 and pegylated-Che6. They were exposed to a diode laser emitting at 670 nm wave length with total radiation dose of 6 J/cm2. Cell viability was determined by MTT assay. Production level of singlet oxygen was detected with photomultiplier-tube based singlet oxygen detection system. An antitumor PDT effects in AsPC-1 cellbearing BALC/nude mice of the Che6 and pegylated-Che6 were investigated. Results : The