The effect of guanidinylation of PEGylated poly(2-aminoethyl methacrylate) on the systemic delivery of siRNA

Qiang Cheng, Yuanyu Huang, Hua Zheng, Tuo Wei, Shuquan Zheng, Shuaidong Huo, Xiaoxia Wang, Quan Du, Xiaoning Zhang, Hong Yan Zhang, Xing Jie Liang, Chun Wang, Rupei Tang, Zicai Liang

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43 Scopus citations


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 N/. P ratio. These findings set the stage for further studies of structural-functional mechanisms and developments of siRNA therapeutics.

Original languageEnglish (US)
Pages (from-to)3120-3131
Number of pages12
Issue number12
StatePublished - Apr 2013

Bibliographical note

Funding Information:
We thank Jun Zhang (Institute of Molecular Medicine, Peking University) for technical support in cryosection preparation; Junde Yang, Huichen Bai (Suzhou Ribo Life Science Co. Ltd.) for assisting in vivo functional study. This project was supported by grants from the National Drug Program of China (No. 2011ZX09102-011-12 , 2012ZX09102301-006 ), the National Natural Science Foundation of China (No. 81273422 , 31221002 , 21174054 , 21004030 and 51273156 ), the Chinese Program for New Century Excellent Talents in Universities (No. NCET-11-0661 ), the Natural Science Foundation of Jiangsu Province of China (No. BK2010145 ) and the Academic Scholarship for Doctoral Candidates of the Ministry of Education of China . The authors declare there are no conflicts of interest that relate to this paper.


  • Guanidinylation
  • Liver targeting
  • Non-viral carriers
  • PAEM
  • PEG-b-PAEM
  • SiRNA delivery


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