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High gene delivery efficiency of alkylated low-molecular-weight polyethylenimine through gemini surfactant-like effect

Authors Liu S, Huang W, Jin MJ, Wang QM, Zhang GL, Wang XM, Shao S, Gao ZG

Received 21 March 2014

Accepted for publication 27 April 2014

Published 28 July 2014 Volume 2014:9(1) Pages 3567—3581

DOI https://doi.org/10.2147/IJN.S64554

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Shan Liu,1,2 Wei Huang,1,2 Ming-Ji Jin,1,2 Qi-Ming Wang,1,2 Gan-Lin Zhang,3 Xiao-Min Wang,3 Shuai Shao,1,2 Zhong-Gao Gao1,2

1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 2Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, Beijing, People’s Republic of China

Abstract: To our knowledge, the mechanism underlying the high transfection efficiency of ­alkylated low-molecular-weight polyethylenimine (PEI) is not yet well understood. In this work, we grafted branched PEI (molecular weight of 1,800 Da; bPEI1800) with lauryl chains (C12), and found that bPEI1800-C12 was structurally similar to gemini surfactant and could similarly assemble into micelle-like particles. Stability, cellular uptake, and lysosome escape ability of bPEI1800-C12/DNA polyplexes were all greatly enhanced after C12 grafting. bPEI1800-C12/DNA polyplexes exhibited significantly higher transfection efficiency than Lipofectamine™ 2000 in the presence of serum. Bioluminescence imaging showed that systemic injection of bPEI1800-C12/DNA polyplexes resulted in intensive luciferase expression in vivo and bioluminescence signals that could be detected even in the head. Altogether, the high transfection efficacy of bPEI1800-C12 was because bPEI1800-C12, being an analog of gemini surfactant, facilitated lysosome escape and induced the coil–globule transition of DNA to assemble into a highly organized micelle-like structure that showed high stability.

Keywords: self-organization, alkylation, luciferase, bioluminescence imaging

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