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Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma

Authors Wang GM, Gao XL, Gu GJ, Shao ZH, Li MH, Wang PJ, Yang JR, Cai XJ, Li YY

Received 25 December 2016

Accepted for publication 18 April 2017

Published 9 May 2017 Volume 2017:12 Pages 3591—3603


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun

Gangmin Wang,1,* XiaoLong Gao,2,* GuoJun Gu,2 ZhiHong Shao,2 MingHua Li,2 PeiJun Wang,2 JianRong Yang,3 XiaoJun Cai,4 YongYong Li4

1Department of Urology, Huashan Hospital, Fudan University, 2Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 3Department of Hepatobiliary Surgery, Third People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 4Institute for Advanced Materials and Nano Biomedicine, School of Material Science and Engineering, Tongji University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract: A polyethylene glycol–poly(ε-benzyloxycarbonyl-l-lysine) (PEG-SS-PLL) block copolymer based on a disulfide-linked, novel biodegradable catiomer bearing a PEG-sheddable shell was developed to avoid “PEG dilemma” in nanoparticle intracellular tracking of PEG-PLL where PEG was nondegradable. However, PEG-SS-PLL catiomers have not been used to deliver small interfering VEGF RNA (siVEGF) in antiangiogenesis gene therapy. In this study, we aimed to investigate whether this novel biodegradable catiomer can deliver siVEGF into cancer cells and at the same time have an antitumor effect in a xenograft mouse model. It was found that PEG-SS-PLL efficiently delivered siVEGF with negligible cytotoxicity, and significantly decreased the expression of VEGF at both the messenger-RNA and protein levels both in vitro and in vivo, and thus tumor growth was inhibited. Our findings demonstrated that PEG-SS-PLL/siVEGF could potentially be applied to antiangiogenesis gene therapy for hepatocellular carcinoma.

Keywords: polyethylene glycol, poly lysine, disulfide, VEGF, antiangiogenesis, hepatocellular carcinoma, siRNA

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