用于靶向递送 siRNA 的重组高密度脂蛋白纳米颗粒。
Recombinant high density lipoprotein nanoparticles for target-specific delivery of siRNA.
机构信息
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China.
出版信息
Pharm Res. 2013 May;30(5):1203-14. doi: 10.1007/s11095-012-0957-4. Epub 2012 Dec 14.
PURPOSE
Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for treatments of numerous diseases. However, the progress towards broad application of siRNA requires the development of safe and effective vectors that target to specific cells. In this study, we developed a novel recombinant high density lipoprotein (rHDL) vector with high siRNA encapsulation efficiency.
METHODS
They were prepared by condensing siRNA with various commercial cationic polymers and coating the polyplex with a layer of lipids and apolipoprotein AI (apo AI). The rHDL nanoparticles were used to transfect SMMC-7721 hepatoma cells with stable luciferase expression. The uptake and intracellular trafficing of siRNA were also investigated.
RESULTS
Characterization studies revealed these rHDL nanoparticles had similar physical properties as natural HDLs. The various rHDL formulations had high silencing efficiency (more than 70% knockdown) in hepatocytes with minimum cytotoxicity. Moreover, the uptake of rHDL by SMMC-7721 was confirmed to be mediated through the natural HDL uptake pathway.
CONCLUSIONS
The work described here demonstrated the optimized rHDL nanoparticles may offer a promising tool for siRNA delivery to the liver.
目的
利用小干扰 RNA（siRNA）调控基因表达是治疗多种疾病的一种很有前途的策略。然而，siRNA 的广泛应用需要开发针对特定细胞的安全有效的载体。在本研究中，我们开发了一种新型重组高密度脂蛋白（rHDL）载体，具有较高的 siRNA 包封效率。
方法
通过将 siRNA 与各种商业阳离子聚合物缩合，并在多聚物层上覆盖一层脂质和载脂蛋白 AI（apoAI），制备 rHDL 纳米颗粒。将 rHDL 纳米颗粒用于转染具有稳定荧光素酶表达的 SMMC-7721 肝癌细胞。还研究了 siRNA 的摄取和细胞内运输。
结果
特性研究表明，这些 rHDL 纳米颗粒具有与天然 HDL 相似的物理特性。各种 rHDL 制剂在具有最小细胞毒性的情况下对肝细胞具有很高的沉默效率（超过 70%的基因敲低）。此外，通过 SMMC-7721 摄取 rHDL 被证实是通过天然 HDL 摄取途径介导的。
结论
这里描述的工作表明，优化的 rHDL 纳米颗粒可能为 siRNA 向肝脏的递呈提供一种很有前途的工具。
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