Department of Pharmacy , China Pharmaceutical University , Nanjing 211198 , PR China.
Mol Pharm. 2018 Oct 1;15(10):4558-4567. doi: 10.1021/acs.molpharmaceut.8b00549. Epub 2018 Aug 27.
The development of non-viral vectors for gene delivery has gained attention over the past decades. Specifically, poly(β-amino ester) (PBAE) has shown great potential for improving the delivery of gene therapeutics. It has been observed that low-molecular-weight PBAE displayed low transfection activities, while quaternization could enhance the transgene expression efficacy of PBAE. Herein, PBAE quaternary ammonium salt (PBAEQAS) was synthesized to increase the positive charge of the polymers, which resulted in an increase in siRNA binding efficiency based on self-assembly electrostatic interaction. Specifically, the nanoparticle surface was positively charged, which increased the uptake ability of siRNA. Compared with acrylate-PBAEQAS/siNC nanoparticles and amine-PBAEQAS/siNC nanoparticles, acrylate-PBAEQAS/siSurvivin nanoparticles and amine-PBAEQAS/siSurvivin nanoparticles induced more-efficient cell apoptosis and gene silencing. All these results suggest that PBAEQAS would be a promising gene delivery vector for cancer treatment.
在过去的几十年中，非病毒载体的基因传递发展受到了关注。具体来说，聚（β-氨基酯）（PBAE）在改善基因治疗药物的传递方面显示出巨大的潜力。已经观察到低分子量 PBAE 的转染活性低，而季铵化可以增强 PBAE 的转基因表达效果。在此，合成了聚（β-氨基酯）季铵盐（PBAEQAS）以增加聚合物的正电荷，这导致基于自组装静电相互作用的 siRNA 结合效率增加。具体而言，纳米颗粒表面带正电荷，增加了 siRNA 的摄取能力。与丙烯酸酯-PBAEQAS/siNC 纳米颗粒和胺基-PBAEQAS/siNC 纳米颗粒相比，丙烯酸酯-PBAEQAS/siSurvivin 纳米颗粒和胺基-PBAEQAS/siSurvivin 纳米颗粒诱导更有效的细胞凋亡和基因沉默。所有这些结果表明，PBAEQAS 将成为治疗癌症的有前途的基因传递载体。
