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.

基于小干扰RNA（siRNA）的疗法因其靶标特异性基因沉默而成为一种强大的治疗工具。然而，由于细胞吸收不良而限制了治疗功效，因此需要递送载体来改善细胞吸收。在本文中，开发了结合胍基的聚醚基嵌段共聚电解质以改善细胞摄取并因此提高了基因沉默效率。胍基官能化的聚环氧乙烷-b-烯丙基缩水甘油醚的活性阴离子开环聚合反应，并进行后修饰以引入胍基，从而制得-烯丙基缩水甘油醚（G-PEO-PAGE）。G-PEO-PAGE由于在生理pH下胍基具有高阳离子电荷，因此可与siRNA高效复合，从而显着提高了siRNA的细胞摄取，从而提高了基因沉默效率。此外，与市售的支链聚乙烯亚胺相比，G-PEO-PAGE显示出明显更低的细胞毒性。这项研究表明，结合胍基的嵌段共聚电解质具有高效和低毒性的siRNA传递的巨大潜力。