Lee Soo Hyeon, Bae Ki Hyun, Kim Sun Hwa, Lee Kyu Ri, Park Tae Gwan
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Int J Pharm. 2008 Nov 19;364(1):94-101. doi: 10.1016/j.ijpharm.2008.07.027. Epub 2008 Aug 3.
Gold nanoparticles chemically modified with primary amine groups were developed as intracellular delivery vehicles for therapeutic small interfering RNA (siRNA). The positively charged gold nanoparticles could form stable polyelectrolyte complexes through electrostatic interactions with negatively charged siRNA-polyethylene glycol (PEG) conjugates having a cleavable di-sulfide linkage under reductive cytosol condition. The resultant core/shell type polyelectrolyte complexes surrounded by a protective PEG shell layer had a well-dispersed nanostructure with a hydrodynamic diameter of 96.3+/-25.9 nm, as determined by dynamic light scattering and transmission electron microscopy. Confocal laser scanning microscopy revealed that the nanosized polyelectrolyte complexes were efficiently internalized in human prostate carcinoma cells, and thus enhanced intracellular uptake of siRNA. Furthermore, the siRNA/gold complexes significantly inhibited the expression of a target gene within the cells without showing severe cytotoxicity. The current study demonstrated that positively charged gold nanoparticles could be potentially applied for intracellular delivery of siRNA.
用伯胺基团化学修饰的金纳米颗粒被开发为治疗性小干扰RNA（siRNA）的细胞内递送载体。带正电荷的金纳米颗粒可通过在还原性细胞质条件下与具有可裂解二硫键的带负电荷的siRNA-聚乙二醇（PEG）共轭物发生静电相互作用，形成稳定的聚电解质复合物。所得的被保护性PEG壳层包围的核/壳型聚电解质复合物具有良好分散的纳米结构，通过动态光散射和透射电子显微镜测定，其流体动力学直径为96.3±25.9nm。共聚焦激光扫描显微镜显示，纳米尺寸的聚电解质复合物能有效地内化于人前列腺癌细胞中，从而增强了细胞内对siRNA的摄取。此外，siRNA/金复合物显著抑制细胞内靶基因的表达，且未表现出严重的细胞毒性。当前研究表明，带正电荷的金纳米颗粒可能潜在地应用于siRNA的细胞内递送。
