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Linear polyethylenimine produced by partial acid hydrolysis of poly(2-ethyl-2-oxazoline) for DNA and siRNA delivery in vitro

Authors Fernandes JC, Qiu X, Winnik FM, Benderdour M, Zhang X, Dai K, Shi Q

Received 30 April 2013

Accepted for publication 8 June 2013

Published 31 October 2013 Volume 2013:8(1) Pages 4091—4102


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Julio C Fernandes,1 Xingping Qiu,2 Françoise M Winnik,2,5 Mohamed Benderdour,1 Xiaoling Zhang,3,4 Kerong Dai,3,4 Qin Shi1

1Orthopaedics Research Laboratory, Research Centre, Sacré-Coeur Hospital, 2Faculty of Pharmacy and Chemistry, University of Montreal, Montreal, Quebec, Canada; 3Orthopaedic Cellular and Molecular Biology Laboratories, Institute of Health Sciences, Chinese Academy of Sciences, 4Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 5WPI International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Ibaraki, Tsukuba, Japan

Abstract: Polyethylenimines (PEIs) are the most efficient synthetic vectors for gene delivery available to date. With its high charge density and strong proton-buffering effect, PEI has an ability to condense DNA and small interfering RNA at physiologic pH. However, the polymer suffers from the disadvantage of high cellular toxicity. To reduce its cellular toxicity, we synthesized linear PEIs by partial hydrolysis of poly(2-ethyl-2-oxazoline). Three linear PEIs with different hydrolysis percentages (30%, 70%, and 96%, respectively) were produced as PEI30, PEI70, and PEI96. PEI30 and PEI96 cannot be considered as suitable transfection agents because of low transfection efficiency (PEI30) or high cellular toxicity (PEI96). PEI70 displayed very weak cell toxicity. The charge density of this polymer (PEI70) was strong enough to condense DNA and small interfering RNA at a physiologic pH of 7.4. Our results also show that PEI70 was highly efficient in DNA delivery and small interfering RNA-mediated knockdown of target genes. Thus, polymers such as PEI70 appear to be very promising vectors for gene delivery.

Keywords: nonviral vector, polyethylenimine, gene delivery, DNA, small interfering RNA

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