聚轮烷超分子衍生物作为基因载体的构建与性能研究
Safe and effective gene delivery is essential to the success of gene therapy.We synthesized and characterized a novel nonviral gene delivery system in which folate (FA) molecules were used as stoppers on cationic polyrotaxanes (PR) composed of polyethylenimine (PEI)600-grafted α-cyclodextrin rings threaded on polyethylene glycol to form FA-terminated PR-PEI600 (FPP).The FA terminal caps of FPP target to cell surfaces abundant in FA receptor (FR),a common feature of tumor cells.We characterized the structure of FPP and measured its in vitro and in vivo transfection efficiency and cytotoxicity.The new gene vector was composed of chemically bonded PEG (4000),a-CD,and PEI (600 Da) at a molar ratio of 1: 17: 86.7.FPP/pDNA polyplexes at N/P ratios 20 were condensed to diameters less than 140 nm,and were associated with zeta potentials less than 30 mV.FPP/pDNA exhibited lower cytotoxicity than PEI-25 kDa/pDNA.In vitro,the transfection efficiency of FPP/pDNA ranged from 50–70% and could be improved by the addition of albumin.Furthermore,FPP /DNA complexes transfected tumour cells more effectively than PEI 25K in vivo after intratumoral injection and intravenous (i.v.) administration.Together,these results suggest that FPP,which has improved transfection efficiency and tumour specificity both in vitro and in vivo,may be useful for gene therapy.
supramolecule cyclodextrin polyethylenimine folate receptor targeting gene carrier
Jian-hai Chen Yi Zhou Yong-Nan Jiang Wen-feng Lu Shui-fang Chen Jian-bing Zhao Le Lai
Department of pharmaceutical science,Nanfang hospital,Southern Medical University,Guangzhou 510515,China
国内会议
南京
中文
1-19
2012-11-01（万方平台首次上网日期，不代表论文的发表时间）