Chen Jin-Liang, Wang Hua, Gao Jian-Qing, Chen Hai-Liang, Liang Wen-Quan
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.
Int J Pharm. 2007 Oct 1;343(1-2):255-61. doi: 10.1016/j.ijpharm.2007.05.045. Epub 2007 May 25.
Gene therapy provides great opportunities for treating diseases from genetic disorders, infections and cancer. The development of efficient and safe gene transfer systems could be one of the most important factors for successful gene therapy. In the present study, an amphiphilic compound, polyethylenimine (PEI, MW 800)-cholesterol (PEI 800-Chol), firstly designed to modify the surface of liposomes, was synthesized. Polycation liposomes (PCLs) composed of soybean phospholipids (SPL), cholesterol (Chol) and PEI 800-Chol were prepared using film hydration method. The mean particle size of the PCLs was 133.0 nm and the zeta potential was 50.1+/-2.6 mV. Due to the PEI anchored onto the surface of liposomes, higher buffering capacity of PCLs was observed, indicating the potential for buffering in the acidic pH environment of the endosomes. Compared to Lipofectamine 2000, PCLs have equivalent transfection efficiency with significantly low cytotoxicity. Interestingly, the transfection activity of PCLs was not influenced in the presence of serum. Furthermore, we constructed another PCL composed of PEI 800-Chol and DOPE, and transfection efficiency increased notably. In conclusion, the PCLs described in this study have high transfection efficiency with low cytotoxicity, as well as the protection ability from serum, which suggests PCLs would be a potential non-viral gene delivery system.
基因治疗为治疗遗传疾病、感染和癌症等疾病提供了巨大机遇。开发高效且安全的基因传递系统可能是基因治疗成功的最重要因素之一。在本研究中，合成了一种首先设计用于修饰脂质体表面的两亲性化合物，聚乙烯亚胺（PEI，分子量800）-胆固醇（PEI 800-Chol）。采用薄膜水化法制备了由大豆磷脂（SPL）、胆固醇（Chol）和PEI 800-Chol组成的聚阳离子脂质体（PCLs）。PCLs的平均粒径为133.0 nm，zeta电位为50.1±2.6 mV。由于PEI锚定在脂质体表面，观察到PCLs具有更高的缓冲能力，表明其在内体酸性pH环境中具有缓冲潜力。与Lipofectamine 2000相比，PCLs具有相当的转染效率且细胞毒性显著较低。有趣的是，PCLs的转染活性在血清存在的情况下不受影响。此外，我们构建了另一种由PEI 800-Chol和DOPE组成的PCL，其转染效率显著提高。总之，本研究中描述的PCLs具有高转染效率和低细胞毒性，以及血清保护能力，这表明PCLs将是一种潜在的非病毒基因递送系统。
