基于聚(L-谷氨酸)树状分子的智能药物释放系统研究  

DENDRITIC POLY(L-GLUTAMIC ACID) BASED SMART DRUG DELIVERY SYSTEM

作　　者：江超[1] 盛明明[1] 何斌[1] 王刚[1] 吴尧[1] 顾忠伟[1] 

机构地区：[1]四川大学国家生物医学材料工程技术研究中心,成都610064

出　　处：《高分子学报》2011年第8期845-852,共8页Acta Polymerica Sinica

基　　金：四川省国际合作项目(项目号2009HH0001);科技部国际合作项目(项目号2010DFA51550);国家重点基础研究发展计划(973计划;项目号2011CB606206)

摘　　要：以天然氨基酸L-谷氨酸为原料,通过收敛法合成了聚(L-谷氨酸)树状分子,通过半胱氨酸将抗肿瘤药物甲氨蝶呤(MTX)键合到聚(L-谷氨酸)树状分子上,构建氧化还原敏感的药物传输系统.用核磁(1H-NMR)等对载体以及载药粒子进行了表征.体外释放研究发现,载药粒子具有良好的氧化还原响应性,在不同浓度的还原剂二硫苏糖醇(DTT)作用下药物的释放速率明显不同,当DTT=10 mmol/L时,药物释放较快,DTT=2 mmol/L次之,而DTT=0.2 mmol/L时无释放现象.体外细胞实验结果表明,聚(L-谷氨酸)树状分子的细胞毒性低,载药粒子对HepG2细胞的增殖有明显的抑制作用.A redox-sensitive drug delivery system was fabricated.Dendritic poly（L-glutamic acid） was synthesized.Anti-tumor drug methotrexate（MTX） was immobilized on the dendritic poly（L-glutamic acid） via disulfide bonds using cystines as linkers.The disulfide bond was sensitive to glutathione in intracellular environment,thus to release the MTX from the dendritic poly（L-glutamic acid） backbones.The dendritic poly（L-glutamic acid） backbones and drug loaded conjugates were characterized by nuclear magnetic resonance（NMR）.The release profiles of the conjugates were investigated in phosphate buffer saline（PBS） with dithiothreitol（DTT） to simulate the intracellular environment;the results showed that the release rates were closely dependant on the concentration of DTT.Higher DTT concentration resulted in faster release.When the DTT concentration was lower than 0.2 mmol/L,MTX was not released from dendritic backbones.The conjugates were incubated with HepG2 cells to evaluate their anti-tumor effect in vitro.The dendritic poly（L-glutamic acid） was nontoxic to cells even when its concentration was as high as 20 μg/mL.The inhibition effect of the conjugates on tumor cells was better than that of free MTX after incubation for 72 h.Fluorescein isothiocyanate（FITC） was immobilized on the dendrmers and conjugates to trace the endocytosis.The MTX could promote the cell uptake for its folic acid mimetic structure.

关 键 词：聚(L-谷氨酸)树状分子 甲氨蝶呤(MTX) 氧化还原敏感 药物传输系统 

分 类 号：TQ460.1[化学工程—制药化工]