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基因递送中磁性阳离子脂质体的制备与表征

Preparation and characterization of magnetic cationic liposome in gene delivery.

作者信息

Zheng Xiaoli, Lu Jianping, Deng Li, Xiong Yang, Chen Jianming

机构信息

Department of Pharmaceutics, School of Pharmacy, The Second Military Medical University, Shanghai 200433, PR China.

出版信息

Int J Pharm. 2009 Jan 21;366(1-2):211-7. doi: 10.1016/j.ijpharm.2008.09.019. Epub 2008 Sep 20.

Abstract

Low transfection efficiency in vivo and failure to deliver therapeutic nucleic acids to the target organs limit the use of cationic liposomes (CLs) in gene therapy. Magnetic drug targeting (MDT) was applied in this study to improve the transfection efficiency and overcome the limitations. Magnetic cationic liposomes (MCLs) were prepared by incorporating MAG-T (magnetite) into CLs. The inclusion of relatively high concentration of MAG-T significantly increased the size of liposomes/lipoplexes, reduced the zeta potential, and decreased the cell viability. The transfection efficiency of MCLs in gene delivery was evaluated by using plasmid DNA (pDNA) containing a luciferase reporter gene in THLE-3 cells. Results suggested that the transfection efficiency of MCLs/pDNA complexes with a relatively lower content of MAG-T (0.75 mg/ml) was the same as that of CLs/pDNA complexes without a magnetic field but was higher (about 2.6-fold) with magnetic induction. Finally, using MCLs/pDNA complexes and a static magnetic field placed over the liver of rats, luciferase reporter gene expression in the liver increased as compared to MCLs/pDNA complexes and CLs/pDNA complexes in the absence of an external magnetic field.

摘要

体内转染效率低以及无法将治疗性核酸递送至靶器官限制了阳离子脂质体(CLs)在基因治疗中的应用。本研究应用磁靶向给药(MDT)来提高转染效率并克服这些限制。通过将MAG-T(磁铁矿)掺入CLs中来制备磁性阳离子脂质体(MCLs)。加入相对高浓度的MAG-T会显著增加脂质体/脂质复合物的大小,降低zeta电位,并降低细胞活力。通过在THLE-3细胞中使用含有荧光素酶报告基因的质粒DNA(pDNA)来评估MCLs在基因递送中的转染效率。结果表明,MAG-T含量相对较低(0.75 mg/ml)的MCLs/pDNA复合物的转染效率与无磁场的CLs/pDNA复合物相同,但在磁感应下更高(约2.6倍)。最后,使用MCLs/pDNA复合物并在大鼠肝脏上方放置静磁场,与无外部磁场的MCLs/pDNA复合物和CLs/pDNA复合物相比,肝脏中的荧光素酶报告基因表达增加。

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