Delivery of EZH2-shRNA with mPEG-PEI nanoparticles for the treatment of prostate cancer in vitro.

ABSTRACT

Small interfering RNA (siRNA) is a promising therapeutic approach for castration-resistant prostate cancer (PCa). For the clinical application of siRNA, it is vital to find a safe and efficient gene transfer vector. Nanotechnology can provide a crucial advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of new therapeutic delivery vehicles. In this study, we describe a novel nanoparticle (mPEG-PEI) as an efficient non-viral carrier and found that this copolymer displayed enhanced efficiency in the shRNA-mediated knockdown of target genes. The enhancer of zeste homolog 2 (EZH2) is often elevated in castration-resistant PCa and has been implicated in the progression of human PCa. Targeting EZH2 may have therapeutic efficacy for the treatment of metastatic, hormone-refractory PCa. mPEG-PEI binds plasmid DNA yielding nanoparticles and these complexes exhibit low cytotoxicity and high gene transfection efficiency. Taken together, mPEG-PEI may be a promising non-viral gene carrier for the delivery of EZH2 short hairpin (sh)RNA to PC3 cells for advanced PCa therapy.