(645g) Sensitization of Cancer Cells to Chemotherapy through Efficient siRNA Delivery by Cationic Polymer Core/Shell Nanoparticles

In this study, cationic nanoparticles self- assembled from the amphiphilic copolymer poly (N-methyldietheneaminesebacate) - co - [(cholesteryl oxocarbonylamido ethyl) methyl bis (ethylene) ammonium bromide] sebate) (P(MDS-co-CES) were fabricated and used to deliver Bcl-2 and CCND1 targeted siRNA into PC-3 and MCF-7 cells. The nanoparticles were prepared in various pH conditions, which resulted in nanoparticles with different size, zeta potential, and siRNA binding capabilities. Nanoparticles formed in pH 6 retained high siRNA delivery efficiency as in pH 5 but with much lower cytotoxicity. Bcl-2 and CCND1 mRNA expression were silenced by about 80% upon siRNA transfection as examined by real time RT-PCR. The results were confirmed further through western blot. Co-delivery of Bcl-2 and CCND1 siRNA enhanced the cytotoxicity effect of paclitaxol to MCF-7 cells by 40% and of tamoxifen by 30% to the same cell line. A similar trend was observed in PC-3 cells for paclitaxol treatment. Thus, these cationic nanoparticle/siRNA complexes may be employed to treat late stage cancers with overexpression of Bcl-2 and CCND1, and with resistance to chemotherapy treatment.