Department of Pharmaceutical Science, School of Pharmacy, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, People's Republic of China.
Int J Pharm. 2010 May 10;390(2):198-207. doi: 10.1016/j.ijpharm.2010.01.035. Epub 2010 Jan 29.
Cationic liposomes (CLs) composed of 3beta-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidylethanolamine (DOPE) (DC-Chol/DOPE liposomes) have been classified as one of the most efficient gene delivery systems. Our study aims to examine the effect of the molar ratio of DC-Chol/DOPE, PEGylation and serum on the pDNA (plasmid pDNA) and siRNA (small interfering RNA) transfection of DC-Chol/DOPE liposomes. The results showed that the most efficient DC-Chol/DOPE liposomes for pDNA or siRNA delivery were at a 1:2 or 1:1 molar ratio of DC-Chol/DOPE, respectively. The transfection efficiency of DC-Chol/DOPE liposomes increased along with increased weight ratio of DC-Chol/siRNA. However, the pDNA transfection efficiency decreased along with increased weight ratio of DC-Chol/pDNA from 3/1. As expected, PEGylation decreased siRNA and pDNA transfection efficiency of DC-Chol/DOPE liposomes. In PEGylated DC-Chol/DOPE liposomes, increased weight ratio of DC-Chol/pDNA from 3/1 did not lead to higher pDNA transfection efficiency, whereas increased weight ratio of DC-Chol/siRNA resulted in increased siRNA transfection efficiency. Furthermore, the serum did not significantly inhibit the pDNA and siRNA transfection efficiency of DC-Chol/DOPE liposomes. In conclusion, our results elucidated the influence factors of DC-Chol/DOPE liposome transfection and would reveal that siRNA and pDNA transfection mechanisms were different in DC-Chol/DOPE liposomes.
阳离子脂质体（CL）由 3β-[N-（N'，N'-二甲氨基乙酰胺基）氨基甲酰基]胆固醇（DC-Chol）和二油酰基磷脂酰乙醇胺（DOPE）组成（DC-Chol/DOPE 脂质体）被归类为最有效的基因传递系统之一。我们的研究旨在研究 DC-Chol/DOPE 的摩尔比、PEG 化和血清对 pDNA（质粒 pDNA）和 siRNA（小干扰 RNA）转染 DC-Chol/DOPE 脂质体的影响。结果表明，用于 pDNA 或 siRNA 传递的最有效的 DC-Chol/DOPE 脂质体分别为 DC-Chol/DOPE 的摩尔比为 1:2 或 1:1。随着 DC-Chol/siRNA 的重量比增加，DC-Chol/DOPE 脂质体的转染效率增加。然而，随着 DC-Chol/pDNA 的重量比从 3/1 增加，pDNA 的转染效率降低。正如预期的那样，PEG 化降低了 DC-Chol/DOPE 脂质体的 siRNA 和 pDNA 转染效率。在 PEG 化的 DC-Chol/DOPE 脂质体中，随着 DC-Chol/pDNA 的重量比从 3/1 增加，pDNA 的转染效率不会增加，而 DC-Chol/siRNA 的重量比增加会导致 siRNA 的转染效率增加。此外，血清不会显着抑制 DC-Chol/DOPE 脂质体的 pDNA 和 siRNA 转染效率。总之，我们的结果阐明了 DC-Chol/DOPE 脂质体转染的影响因素，并揭示了 siRNA 和 pDNA 在 DC-Chol/DOPE 脂质体中的转染机制不同。
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