Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
University of Science and Technology of China, Hefei 230026, China.
Biomacromolecules. 2022 Jul 11;23(7):2867-2877. doi: 10.1021/acs.biomac.2c00331. Epub 2022 Jun 9.
The relatively low transfection efficiency limits further application of polymeric gene carriers. It is imperative to exploit a universal and simple strategy to enhance the gene transfection efficiency of polymeric gene carriers. Herein, we prepared a cationic polypeptide poly(γ-aminoethylthiopropyl-l-glutamate) (PALG-MEA, termed PM) with a stable α-helical conformation, which can significantly improve the gene transfection efficiency of cationic polymers. PM can be integrated into polymeric gene delivery systems noncovalently through electrostatic interactions. With the assistance of PM, polymeric gene delivery systems exhibited excellent cellular uptake and endosomal escape, thereby enhancing transfection efficiency. The transfection enhancement effect of PM was applicable to a variety of cationic polymers such as polyethylenimine (PEI), poly-l-lysine (PLL), and polyamidoamine (PAMAM). The ternary gene delivery system PM/pshVEGF/PEI exhibited an excellent antitumor effect against the B16F10 tumor model. Moreover, we demonstrated that PM could also enhance the delivery of gene editing systems (sgRNA-Cas9 plasmids). This work provides a facile and effective strategy for constructing polymeric gene delivery systems with a high transfection efficiency.
相对较低的转染效率限制了聚合物基因载体的进一步应用。因此，迫切需要开发一种通用且简单的策略来提高聚合物基因载体的基因转染效率。本文制备了一种具有稳定α-螺旋构象的阳离子多肽聚（γ-氨基乙基硫代丙基-l-谷氨酸）（PALG-MEA，称为 PM），其能显著提高阳离子聚合物的基因转染效率。PM 可通过静电相互作用非共价地整合到聚合物基因传递系统中。在 PM 的辅助下，聚合物基因传递系统表现出优异的细胞摄取和内涵体逃逸能力，从而增强转染效率。PM 的转染增强效果适用于多种阳离子聚合物，如聚乙烯亚胺（PEI）、聚赖氨酸（PLL）和聚酰胺-胺（PAMAM）。三元基因传递系统 PM/pshVEGF/PEI 对 B16F10 肿瘤模型表现出优异的抗肿瘤作用。此外，我们证明 PM 还可以增强基因编辑系统（sgRNA-Cas9 质粒）的传递。这项工作为构建具有高转染效率的聚合物基因传递系统提供了一种简便有效的策略。
