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The effect of guanidinylation of PEGylated poly(2-aminoethyl methacrylate) on the systemic delivery of siRNA
Cheng, Qiang1; Huang, Yuanyu1; Zheng, Hua2; Wei, Tuo5; Zheng, Shuquan1; Huo, Shuaidong5; Wang, Xiaoxia1; Du, Quan1,6; Zhang, Xiaoning7; Zhang, Hong-Yan3; Liang, Xing-Jie5; Wang, Chun4; Tang, Rupei2; Liang, Zicai1
关键词siRNA delivery PAEM PEG-b-PAEM Guanidinylation Liver targeting Non-viral carriers
刊名BIOMATERIALS
2013-04-01
DOI10.1016/j.biomaterials.2013.01.043
34期:12页:3120-3131
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]SMALL-INTERFERING RNA ; GENE DELIVERY ; IN-VIVO ; ANTIINFLAMMATORY TREATMENT ; RADICAL POLYMERIZATION ; TERNARY COMPLEXES ; TARGETED DELIVERY ; DENDRITIC CELLS ; CHAIN-LENGTH ; CANCER-CELLS
英文摘要

Small interfering RNA (siRNA) has a huge potential for the treatment or prevention of various diseases. However, to realize the therapeutic potential of siRNA drugs, efficient, tissue-specific and safe delivery technologies must be developed. Here we synthesized two kinds of polymers (PEGylated poly(2-aminoethyl methacrylate) labeled as PEG-b-PAEM or PEA, and guanidinylated PEGylated poly(2-aminoethyl methacrylate) marked as PEG-b-PAEM-co-PGEM or PEAG) using atom transfer radical polymerization and evaluated their capability of mediating siRNA delivery in vitro and in vivo. Both polymers presented excellent siRNA encapsulation ability, formed regular nanostructures with siRNA, robustly mediated cellular internalization and cytoplasmic localization of siRNA, and resulted in targeted gene knockdown efficiently. However, PEAG showed much more outstanding abilities referring to above evaluating indicators compared with PEA. Both PEA/siRNA and PEAG/siRNA polyplexes displayed strong liver, lung and spleen accumulation in mice for a long time after intravenous administration. PEAG/siApoB polyplexes (single dose at 1 mg/kg) further repressed ApoB expression in liver and resulted in block of lipid transportation. In addition, both polymers delivered high amounts of siRNA into tumor tissue in the Hela-Luc xenograft murine model. More siRNA accumulated in tumor with the increase of N/P ratio and PEAG/siRNA polyplexes showed higher siRNA accumulation than PEA/siRNA polyplexes at the same NIP ratio. These findings set the stage for further studies of structural functional mechanisms and developments of siRNA therapeutics. (C) 2013 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000316038900026
项目编号2011ZX09102-011-12 ; 2012ZX09102301-006 ; 81273422 ; 31221002 ; 21174054 ; 21004030 ; 51273156 ; NCET-11-0661 ; BK2010145
资助机构National Drug Program of China ; National Natural Science Foundation of China ; Chinese Program for New Century Excellent Talents in Universities ; Natural Science Foundation of Jiangsu Province of China ; Academic Scholarship for Doctoral Candidates of the Ministry of Education of China
引用统计
被引频次:28[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67323
专题北京大学药学院
作者单位1.Suzhou Ribo Life Sci Co Ltd, Kunshan 215300, Jiangsu, Peoples R China
2.Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China
3.Jiangnan Univ, Sch Med & Pharmaceut, Wuxi 214122, Peoples R China
4.Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA
5.Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China
6.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
7.Tsinghua Univ, Sch Med, Lab Pharmaceut, Beijing 100084, Peoples R China
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GB/T 7714
Cheng, Qiang,Huang, Yuanyu,Zheng, Hua,et al. The effect of guanidinylation of PEGylated poly(2-aminoethyl methacrylate) on the systemic delivery of siRNA[J]. BIOMATERIALS,2013,34(12):3120-3131.
APA Cheng, Qiang.,Huang, Yuanyu.,Zheng, Hua.,Wei, Tuo.,Zheng, Shuquan.,...&Liang, Zicai.(2013).The effect of guanidinylation of PEGylated poly(2-aminoethyl methacrylate) on the systemic delivery of siRNA.BIOMATERIALS,34(12),3120-3131.
MLA Cheng, Qiang,et al."The effect of guanidinylation of PEGylated poly(2-aminoethyl methacrylate) on the systemic delivery of siRNA".BIOMATERIALS 34.12(2013):3120-3131.
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