Guanidinium-Incorporated Micelleplexes for Low Toxic and Efficient siRNA Delivery
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Article www.springer.com/13233 pISSN 1598-5032 eISSN 2092-7673
Guanidinium-Incorporated Micelleplexes for Low Toxic and Efficient siRNA Delivery Quan Truong Hoang†,1 Tae-Young Heo†,2 Dae Gun Choi1 Soo-Hyung Choi*,2 Min Suk Shim*,1
1 2
Division of Bioengineering, Incheon National University, Incheon 22012, Korea Department of Chemical Engineering, Hongik University, Seoul 04066, Korea.
Received June 13, 2020 / Revised July 28, 2020 / Accepted Jult 28, 2020
Abstract: Small interfering RNA (siRNA)-based therapy has emerged as a powerful therapeutic tool due to its target-specific gene silencing. However, the therapeutic efficacy has been limited by poor cellular uptake, and therefore delivery vehicles are required to improve the cellular uptake. Herein, guanidinium-incorporated polyether-based block copolyelectrolytes were developed for improved cellular uptake and consequently increased gene silencing efficiency. Guanidinium-functionalized poly(ethylene oxide-b-allyl glycidyl ether) (G-PEO-PAGE) were prepared by living anionic ring opening polymerization of allyl glycidyl ether and post-modification to introduce guanidinium groups. G-PEO-PAGE provides efficient complexation with siRNA due to highly cationic charges of the guanidinium groups at physiological pH, resulting in significantly improved cellular uptake of siRNA and consequently increased gene silencing efficiency. In addition, G-PEO-PAGE showed significantly lower cytotoxicity compared to branched polyethylenimine as a commercial counterpart. This study demonstrates that guanidinium-incorporated block copolyelectrolytes have a great potential for efficient and low toxic siRNA delivery. Keywords: Guanidinium, block copolyelectrolytes, siRNA, RNA interference, micelleplex, nanoparticle.
1. Introduction RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression by destabilizing targeted messenger RNA (mRNA).1 Small interfering RNA (siRNA) complementary to the target mRNA has emerged as a powerful therapeutic tool due to its specific inhibition of disease-related genes.2,3 Despite the great potential of siRNA-based therapy, the use of siRNA in the clinic has been limited due to its poor intracellular delivery into target cells.4-6 Therefore, it is crucial to develop efficient siRNA carriers to improve the intracellular delivery of siRNA.7-10 To date, various nanoscale siRNA carriers using polymers,11,12 cationic lipids13 or peptides14 have been widely explored for effective siRNA delivery. Recently, polymeric nanoparticles have attracted great attention owing to their superior properties including versatility, biocompatibility, and stability.15,16 In particular, cationic polymers such as polyethylenimine (PEI) and chitosan have attracted great attention as efficient siRNA carriers.17-19 Because of negative net charge of siRNA, cationic polymers can form stable and compact polyplexes with siRNA by electrostatic interaction. Acknowledgments: This work was supported by Research Assistance Program (2019) in the Incheon Nati
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