Dr BR Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
Eur J Pharm Biopharm. 2009 Sep;73(1):43-9. doi: 10.1016/j.ejpb.2009.04.001. Epub 2009 Apr 10.
Degradation of mRNA by RNA interference is one of the most powerful and specific mechanism for gene silencing. Owing to this property, siRNAs are emerging as promising therapeutic agents for the treatment of inherited and acquired diseases, as well as research tools for the elucidation of gene function in both health and disease. Here we have explored the potential of polyethylenimine (PEI) to deliver siRNA to mammalian cells. Nanoparticles of PEI were prepared by acylating PEI with propionic anhydride followed by cross-linking with polyethylene glycol-bis(phosphate). The nanoparticles size as revealed by DLS studies was found to be approximately 110 nm and AFM investigations showed spherical and compact complexes with an average size of 100 nm. For electro-neutralization of negative charge of siRNA higher amount of nanoparticles was required as compared to native PEI. The siRNA delivery efficiency of nanoparticles was assessed by using siRNA against gene coding for green fluorescent protein (GFP). The gene silencing efficiency of PEI nanoparticles was found to be comparable to commercially available transfecting agent Lipofectin but with reduced cytotoxicity.
RNA 干扰导致的 mRNA 降解是基因沉默最有效和最特异的机制之一。由于这一特性,siRNA 作为治疗遗传性和获得性疾病的有前途的治疗剂,以及阐明健康和疾病中基因功能的研究工具,正在出现。在这里,我们探讨了聚亚乙基亚胺(PEI)将 siRNA 递送至哺乳动物细胞的潜力。通过用丙酸酐酰化 PEI 然后用聚乙二醇-双(磷酸酯)交联来制备 PEI 纳米颗粒。通过 DLS 研究揭示的纳米颗粒大小约为 110nm,AFM 研究表明具有 100nm 左右的平均大小的球形和紧凑复合物。为了中和 siRNA 的负电荷,与天然 PEI 相比,需要更高量的纳米颗粒。通过使用针对编码绿色荧光蛋白(GFP)的基因的 siRNA 评估纳米颗粒的 siRNA 递送效率。PEI 纳米颗粒的基因沉默效率被发现与商业上可获得的转染试剂 Lipofectin 相当,但细胞毒性降低。