普朗尼克—聚乙烯亚胺纳米胶束的制备及其细胞生物学特性

摘要

目的:采用普朗尼克—聚乙烯亚胺纳米胶束制备高效、低毒的药物和基因输送体系.方法:利用小分子量的聚乙烯亚胺作为交联剂制备普朗尼克—聚乙烯亚胺纳米胶束,采用动态光散射法、芘荧光探针法分别测定聚合物的粒径、表面电动电位及临界胶束浓度,考察聚合物携带基因和药物的能力,并在细胞水平上探讨普朗尼克—聚乙烯亚胺的细胞毒性、转染效率以及对细胞内ATP和P-糖蛋白水平的影响.结果:成功制备了普朗尼克—聚乙烯亚胺纳米胶束,其粒径120～180 nm,表面电位+6～ +9 mV,具有良好的携载基因、药物的能力.细胞生物学研究表明,普朗尼克—聚乙烯亚胺毒性较小,其中P123-PEI600基因转染效率高,并且能降低细胞内ATP和P糖蛋白水平.结论:普朗尼克—聚乙烯亚胺是一种良好的药物和基因输送体系,P123-PEI600是理想的可用于逆转肿瘤多药耐药的载体.%Objective:To prepare and characterize Pluronic-PEI micelles as a drug/ gene delivery system.Methods:The low-molecular-weight PEI was used as a cross-linking agent to prepare Pluronic-PEI micelles.The particle size,zeta potential and critical micelle concentration (CMC) were measured by dynamic light scattering (DLS) and pyrene fluorescence probe.The cytotoxicity,transfection efficiency and the impact on the intracellular ATP and P-gp levels of Pluronic-PEI micelles were investigated at the cellular level.Results:Pluronic-PEI micelles were successfully prepared with a suitable particle size (120-180 nm),zeta potential (+ 6-+ 9 mV),and a good ability to carry the drug/gene.An in-vitro study showed that Pluronic-PEI had low cytotoxicity,and the P123-PEI600 possessed high gene transfection efficiency and could downregulate the intracellular ATP and P-gp levels.Conclusion:Pluronic-PEI is a good drug/gene delivery system,and P123-PEI600 is an ideal vector,which may be used in the combination therapy for reversing multidrug resistance.