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

Li,Yun-Hua; Shi,Qiu-Sheng; Du,Jing; Jin,Li-Fang; Du,Lian-Fang; Liu,Pei-Feng; Duan,You-Rong

doi:10.3892/ijmm.2012.1175

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

Authors:
- Yun-Hua Li
- Qiu-Sheng Shi
- Jing Du
- Li-Fang Jin
- Lian-Fang Du
- Pei-Feng Liu
- You-Rong Duan
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Affiliations: Department of Ultrasound, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200080, P.R. China, Cancer Institute of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200032, P.R. China
Published online on: November 8, 2012 https://doi.org/10.3892/ijmm.2012.1175
Pages: 163-171

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Abstract

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.

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