Department of Biological Sciences and Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
J Control Release. 2011 Oct 10;155(1):3-10. doi: 10.1016/j.jconrel.2010.09.009. Epub 2010 Sep 30.
Development of nano-sized gene delivery vehicles for small interfering RNA (siRNA) delivery is of great importance for their clinical applications such as cancer therapy. Herein, we demonstrate the controlled synthesis of polyethyleneimine (PEI)-coated gold nanoparticles (AuNPs) using catechol-conjugated PEI (PEI-C) for siRNA delivery. Since the conjugated catechol groups are reductive and moderately hydrophobic, PEI-C formed spherical multi-cored micelles in aqueous solution and served as reductive templates for the growth and synthesis of spherical AuNPs with tunable sizes and surface charges. PEI-C was stably anchored on the surface of growing crystal gold seeds with crosslinking, resulting in robust cationic AuNPs. The fabricated PEI-coated AuNPs formed stable complexes with siRNA, and the complexes showed an excellent gene silencing effect in cancer cells. Size and surface charge values of the synthesized AuNPs had a great influence on intracellular uptake and unpacking of siRNA, and the resultant gene silencing efficiency. The PEI-coated AuNPs exhibited an extremely low cytotoxicity due to the reduced density of primary amine groups and the absence of uncomplexed PEI fraction in aqueous solution.
用于小干扰 RNA（siRNA）递送的纳米级基因传递载体的开发对于其临床应用（如癌症治疗）非常重要。在此，我们展示了使用儿茶酚缀合的聚乙烯亚胺（PEI-C）可控合成聚乙烯亚胺（PEI）包覆的金纳米颗粒（AuNPs）用于 siRNA 递送。由于共轭儿茶酚基团具有还原性和适度的疏水性，PEI-C 在水溶液中形成球形多核胶束，并作为生长和合成具有可调尺寸和表面电荷的球形 AuNPs 的还原模板。PEI-C 通过交联稳定地锚定在生长的金晶种表面上，形成坚固的阳离子 AuNPs。制备的 PEI 包覆的 AuNPs 与 siRNA 形成稳定的复合物，该复合物在癌细胞中表现出优异的基因沉默效果。合成的 AuNPs 的尺寸和表面电荷值对 siRNA 的细胞内摄取和解包以及由此产生的基因沉默效率有很大影响。由于在水溶液中减少了伯胺基团的密度并且不存在未复合的 PEI 部分，因此 PEI 包覆的 AuNPs 表现出极低的细胞毒性。
