Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma
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 H...
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Dove Medical Press
2017
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oai:doaj.org-article:1bacad2097b341fbbb3c5928b7b6f2802021-12-02T01:13:09ZPolyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma1178-2013https://doaj.org/article/1bacad2097b341fbbb3c5928b7b6f2802017-05-01T00:00:00Zhttps://www.dovepress.com/polyethylene-glycol-polyepsilon-benzyloxycarbonyl-l-lysine-conjuga-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Gangmin 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, siRNAWang GMGao XLGu GJShao ZHLi MHWang PJYang JRCai XJLi YYDove Medical PressarticlePEG-SS-PLLVEGFHepG2Hepatocellular carcinomasiRNA.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3591-3603 (2017) |
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PEG-SS-PLL VEGF HepG2 Hepatocellular carcinoma siRNA. Medicine (General) R5-920 |
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PEG-SS-PLL VEGF HepG2 Hepatocellular carcinoma siRNA. Medicine (General) R5-920 Wang GM Gao XL Gu GJ Shao ZH Li MH Wang PJ Yang JR Cai XJ Li YY Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma |
| description |
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 |
| format |
article |
| author |
Wang GM Gao XL Gu GJ Shao ZH Li MH Wang PJ Yang JR Cai XJ Li YY |
| author_facet |
Wang GM Gao XL Gu GJ Shao ZH Li MH Wang PJ Yang JR Cai XJ Li YY |
| author_sort |
Wang GM |
| title |
Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma |
| title_short |
Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma |
| title_full |
Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma |
| title_fullStr |
Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma |
| title_full_unstemmed |
Polyethylene glycol–poly(ε-benzyloxycarbonyl-L-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma |
| title_sort |
polyethylene glycol–poly(ε-benzyloxycarbonyl-l-lysine)-conjugated vegf sirna for antiangiogenic gene therapy in hepatocellular carcinoma |
| publisher |
Dove Medical Press |
| publishDate |
2017 |
| url |
https://doaj.org/article/1bacad2097b341fbbb3c5928b7b6f280 |
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