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Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery

Authors Yu J, Zhang J, Xing H, Yang Z, Cai C, Zhang C, Zhao X, Wei M, Yang L, Ding P

Received 28 March 2016

Accepted for publication 19 June 2016

Published 17 August 2016 Volume 2016:11 Pages 4011—4024

DOI https://doi.org/10.2147/IJN.S109406

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


Jiankun Yu,1 Jinmin Zhang,1 Haonan Xing,1 Zhen Yang,1 Cuifang Cai,1 Conglu Zhang,1 Xiaoyun Zhao,1 Minjie Wei,2 Li Yang,1 Pingtian Ding1

1School of Pharmacy, Shenyang Pharmaceutical University, 2School of Pharmacy, China Medical University, Shenyang, People’s Republic of China

Abstract: Guanidinylated poly(amido amine)s with multiple disulfide linkages (Gua-SS-PAAs) were designed and constructed as nonviral gene carriers. The main chains of these novel carriers were synthesized based on monomers containing guanidino groups (guanidine hydrochloride and chlorhexidine), which could avoid complicated side-chain-modification reactions while introducing the guanidino groups. The synthesized Gua-SS-PAAs polymers were characterized by 1H nuclear magnetic resonance, molecular weight, and polydispersity. Furthermore, Gua-SS-PAAs polymers were complexed with pDNA, and the properties of the complexes were determined, including entrapment efficiency, particle size, ζ-potential, atomic force microscopy images, stability, DNA complexation ability, reduction sensitivity, cytotoxicity, and transfection efficiency. The new Gua-SS-PAAs carriers exhibited higher transfection efficiency and lower cytotoxicity compared with two widely used gene delivery carriers, polyethylenimine and lipofectamine 2000. Furthermore, the relationship between the side-chain structure and morphological/biological properties was extrapolated, and the results showed that guanidine in the side chain aids in the improvement of transfection efficiency. In addition, the introduction of guanidino group might confer the new carriers with nuclear localization function compared to carriers without it.

Keywords: gene carrier, transfection efficiency, cytotoxicity, nuclear localization, guanidine

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