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Targeted delivery of biodegradable nanoparticles with ultrasound-targeted microbubble destruction-mediated hVEGF-siRNA transfection in human PC-3 cells in vitro.

A potentially viable approach for treating late-stage prostate cancer is             gene therapy. Successful gene therapy requires safe and efficient delivery systems.             In this study, we report the efficient delivery of small interfering RNA (siRNA)             via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene             glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers.             On the basis of previous findings, cyclic Arg-Gly-Asp (cRGD) peptides were conjugated             to NPs to recognize the target site, integrin αvβ3, expressed in high levels in             PC-3 prostate cancer cells. The suppression of angiogenesis by the downregulation             of vascular endothelial growth factor (VEGF) expression has been widely used to             inhibit the growth of malignant tumors. In our study, human VEGF (hVEGF)-siRNA             was encapsulated in NPs to inhibit VEGF expression in PC-3 cells. Concurrently,             sonoporation induced by ultrasound-targeted microbubble destruction (UTMD) was             utilized for the delivery of siRNA-loaded NPs. Our results showed low cytotoxicity             and high gene transfection efficiency, demonstrating that the targeted delivery             of biodegradable NPs with UTMD may be potentially applied as new vector system             for gene delivery.