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用于基因递送的普朗尼克化聚酰胺-胺树状聚合物研究
王翔1,2,丁雪鹰3,武鑫1,丁宝月1,范伟1,高静3,高申1*
0
(1. 第二军医大学长海医院药学部,上海 200433
2. 解放军98医院药械科,湖州 313000
3. 第二军医大学药学院药剂学教研室,上海 200433
*通信作者)
摘要:
目的 合成P123修饰的聚酰胺-胺(PAMAM)聚合物,并研究其作为基因递送载体的可行性。方法 合成及表征了普朗尼克P123修饰的PAMAM树状聚合物,选择A375、293T及HepG2细胞对其进行毒性实验(MTT法),选择HepG2细胞对其与质粒DNA形成的复合物进行转染实验,并与聚乙烯亚胺(PEI)以及未修饰的PAMAM进行比较。 结果聚合物有较高的纯度,粒径电位结果表明复合物符合基因递送的要求,P123修饰PAMAM可以降低细胞毒性,增加细胞体外转染效率。 结论 P123修饰的PAMAM是一种适用于基因递送的新型的聚合物载体。
关键词:  基因  聚酰胺-胺  转染  细胞毒性  普朗尼克
DOI:10.3724/SP.J.1008.2011.0991
投稿时间:2011-03-27修订日期:2011-06-04
基金项目:国家自然科学基金(30973459,30873178,81072100).
Research on pluronic P123ylated polyamidoamine dendrimers for gene delivery
WANG Xiang1,2,DING Xue-ying3,WU Xin1,DING Bao-yue1,FAN Wei1,GAO Jing3,GAO Shen1*
(1. Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
2. Department of Pharmacy, No.98 Hospital of PLA, Huzhou 313000, Zhejiang, China
3. Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
*Corresponding author.)
Abstract:
ObjectiveTo synthesize P123ylated polyamidoamine (PAMAM) copolymers and to evaluate the feasibility of using the copolymers as gene delivery agent. MethodsPluronic P123 modified PAMMA copolymers were synthesized and characterized. The cytotoxicity of the dendrimers was evaluated by the MTT assay using A375, 293T and HepG2 cells. The transfection efficiency of the complexes formed by plasmid with P123ylated PAMAM was evaluated using HepG2 cells. ResultsThe P123ylated PAMAM copolymers had a high purity; the particle sizes and zeta potentials of the complexes were suitable for gene delivery. P123ylated PAMAM could decrease cytotoxicity and increase in vitro transfection efficiency. ConclusionP123ylated PAMAM is a new copolymers agent suitable for gene delivery.
Key words:  gene delivery  polyamidoamine  transfection  cytotoxicity  Pluronic