以磁纳米粒为核的pH敏感型聚谷氨酸树状分子药物载体  

POLY(L-GLUTAMIC ACID) DENDRON BASED pH SENSITIVE DRUG CARRIER WITH MAGNETIC NANOPARTICLE CORE

作　　者：朱荣[1] 罗奎[1] 徐翔晖[1] 吴尧[1] 何斌[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6期679-686,共8页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号50633020;50773046);国家重点基础研究发展计划(973计划;项目号2005CB623903);江苏省自然科学基金(基金号BK2008153)资助项目

摘　　要：报道了一种新的肽类树枝状分子改性磁性纳米药物载体.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,将多巴胺配体键合到聚(L-谷氨酸)树状分子上,用核磁(1H-NMR)、质谱(MS)对合成出的树状分子配体进行了表征,然后通过配体交换对四氧化三铁磁纳米粒表面进行多功能化.以阿霉素为模型药物通过pH敏感的腙键与聚(L-谷氨酸)树状分子外围的官能团结合,将药物负载到磁纳米粒表面构建载药磁纳米粒.用透射电子显微镜(TEM)、动态光散射(DLS)、傅立叶红外光谱(FTIR)、选区电子衍射(SEAD)对纳米药物载体的微观形貌和结构进行了表征,研究结果显示表面功能化后的磁纳米粒在水相中具有很好的分散性和稳定性.纳米载药粒的平均粒径为63 nm,载药量约为52.4 mg g-1.药物释放研究发现,载药粒具有良好的pH响应性,在pH=7.4时释放较慢,而在pH=5.0的微酸性环境释放较快.体外细胞实验结果表明,树状分子改性后的磁纳米粒细胞毒性较低,而载药纳米粒对HeLa细胞的增殖有明显抑制作用.这种pH敏感的聚(L-谷氨酸)树状分子改性磁纳米粒可作为载体用于药物传输系统.Recent advances on targeted drug delivery systems which interact with intracellular components or events such as pH change have been an exciting focus for biomaterials scientists.In present work,poly（L-glutamic acid） peptide dendron was synthesized,and dopamine was immobilized on it as the ligand to substitute the oleic acid on the surface of hydrophobic Fe3O4 magnetic nanoparticles via ligand exchange.The anticancer drug doxorubicin（DOX） was conjugated to the peripheral functional groups of poly（L-glutamic acid） dendron with pH sensitive hydrazine linkers to construct magnetic drug loaded nanocarriers.The structure of the dendron ligand was determined by 1H-NMR and ESI-TOF-MS.The poly（L-glutamic acid） dendron modified magnetic nanoparticles were characterized by TEM,SEAD,DLS and FTIR.The results showed that the crystalline structure of the magnetic cores were not varied after the ligand exchange,the modified magnetic nanoparticles exhibited excellent aqueous dispersity and stability.The DOX loading of modified magnetic nanoparticles with the average size of ca.63 nm was 52.4 mg·g-1.The release rate of DOX from the magnetic nanocarrier in the acid medium（pH=5.0） was dramatically higher than that in the physiological conditions（pH=7.4）.The poly（L-glutamic acid） dendron modified magnetic nanoparticles showed excellent biocompatibility and low cytotoxicity in vitro,and the Fe3O4-G2（Glu）-DOX conjugate was efficient in inhibiting the proliferation of HeLa cells.Therefore,the pH sensitive peptide modified magnetic nanoparticle as a nanocarrier could be effectively utilized in drug delivery system.

关 键 词：聚(L-谷氨酸)树状分子 四氧化三铁磁纳米粒 PH敏感 药物传输系统 

分 类 号：TQ460.1[化学工程—制药化工]