CSIR - Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi, India.
Eur J Pharm Biopharm. 2011 Nov;79(3):473-84. doi: 10.1016/j.ejpb.2011.07.008. Epub 2011 Jul 27.
A series of polyethylenimine (PEI) and γ-polyglutamic acid (PGA) nanocomposites (PPGA) was prepared and evaluated in terms of their cell viability and transfection efficiency in vitro and in vivo. On complexion with pDNA, the positively charged PPGA/DNA nanocomposites resulted in a higher level of in vitro reporter gene transfection (2.7-7.9-fold) as compared to native PEI, and selected commercial reagents and >95% cell viability in HEK293, HeLa and HepG2 cell lines. Further, PPGA-5 nanocomposite (the best working system in terms of transfection efficiency among the series) was found to efficiently transfect primary mouse keratinocytes up to 22% above the control level. PPGA-5, when tested for in vivo cytotoxicity in Drosophila, did not induce any stress in the exposed larvae in comparison with control. In vivo gene expression using PPGA-5 showed the highest transfection efficiency in spleen of mouse closely followed by heart tissues after intravenous injection through tail vein. Besides, these nanocomposites also delivered siRNA efficiently into mammalian cells, resulting in ∼ 80% suppression of EGFP expression. These results together demonstrated the potential of the projected nanocomposites for in vivo gene delivery.
一系列的聚乙烯亚胺（PEI）和γ-聚谷氨酸（PGA）纳米复合材料（PPGA）被制备并评估了其在体外和体内的细胞活力和转染效率。与 pDNA 复合后，带正电荷的 PPGA/DNA 纳米复合材料导致体外报告基因转染水平更高（比天然 PEI 高 2.7-7.9 倍），并且在 HEK293、HeLa 和 HepG2 细胞系中具有 >95%的细胞活力。此外，PPGA-5 纳米复合材料（在该系列中，根据转染效率，是最佳工作系统）被发现能够有效地将原代小鼠角质细胞转染，比对照水平高出 22%。与对照相比，在果蝇中测试 PPGA-5 的体内细胞毒性时，在暴露的幼虫中没有引起任何应激。通过尾静脉静脉内注射后，在体内使用 PPGA-5 进行基因表达显示出最高的转染效率，紧随其后的是心脏组织。此外，这些纳米复合材料还能有效地将 siRNA 递送至哺乳动物细胞，导致 EGFP 表达的抑制率约为 80%。这些结果共同证明了所提出的纳米复合材料在体内基因传递方面的潜力。
