Guanidinium-Incorporated Micelleplexes for Low Toxic and Efficient siRNA Delivery

• Published in: Macromolecular research Vol. 28; no. 12; pp. 1160 - 1165
• Main Authors: Hoang, Quan Truong, Heo, Tae-Young, Choi, Dae Gun, Choi, Soo-Hyung, Shim, Min Suk
• Format: Journal Article
• Language: English
• Published: Seoul The Polymer Society of Korea 01-11-2020; 한국고분자학회
• Subjects: Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Complex Fluids and Microfluidics; Nanochemistry; Nanotechnology; Physical Chemistry; Polymer Sciences; Soft and Granular Matter; 고분자공학; nanoparticle; siRNA; RNA interference; micelleplex; Guanidinium; block copolyelectrolytes
• ISSN: 1598-5032; 2092-7673
• DOI: 10.1007/s13233-020-8152-7

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.