叶酸功能化纳米钻石载药体系的制备及其对C6细胞靶向性研究  

Preparation of Folic Acid Functionalized Nanodiamonds Loading Drug and its Targeted Research of C6 Cells

作　　者：曹瑞霞[1] 田志梅[2] 王东新[2] 王青[1] 李林[2] 李英奇[1,2] 杨斌盛[2] 

机构地区：[1]山西大学化学化工学院,山西太原030006 [2]山西大学分子科学研究所、化学生物学与分子工程教育部重点实验室,山西太原030006

出　　处：《山西大学学报（自然科学版）》2014年第1期91-97,共7页Journal of Shanxi University(Natural Science Edition)

基　　金：国家自然科学基金(21071091);山西省科技攻关计划(社会发展)(20130313021-1);山西省自然科学基金(2009011012-3);山西省回国留学人员科研资助项目(201011)

摘　　要：通过共价偶联的方法制备了聚乙二醇二胺(H2N-PEG-NH2)和叶酸(FA)修饰的纳米钻石(NDs)复合物(ND-PEG-FA),然后在硼酸(BBS,pH 8.0)缓冲溶液中通过物理吸附将小分子药物阿霉素(DOX)附载于NDPEG-FA纳米载体上,制备成ND-PEG-FA/DOX纳米药物。采用紫外-可见分光光谱法和荧光光谱法分别测定了NDs表面偶联NH2-PEG-NH2量为200μg/mg,ND-PEG-NH2表面偶联FA量为44μg/mg以及DOX在ND-PEG-FA纳米载体上的吸附量为(47±1.26)μg/mg.以大鼠神经胶质瘤C6细胞为体外模型肿瘤细胞,利用流式细胞仪(FCM)检测不同浓度的游离叶酸对C6细胞摄取ND-PEG-FA/DOX药物量的影响,结果表明随着游离FA浓度的增加,细胞摄取药物的量因受到游离FA的抑制而明显减少,且最大抑制率可达66.13%,此现象说明制备的ND-PEG-FA/DOX纳米药物进入C6细胞体内为叶酸受体介导机制,同时说明ND-PEG-FA纳米载体具有良好的靶向输送化疗药物的特性。We prepared nanodiamond complexes （ND--PEG--FA）, where nanodiamond conjugated with po- lyethylene glycol diamine （H2N--PEG--NH2） and folic acid （FA） via covalent bond on the carboxylated NDs,following physically adsorbed DOX on the ND--PEG--FA in a borate-buffered solution at pH 8.0 to fabricate targeting drug delivery system of ND--PEG--FA/DOX. The coupled amount of H2N--PEG-- NH2 is 200 /μg/mg on the surface of ND--PEG--NH2 and the coupled amount of FA is 44 μg/mg on the surface of ND--PEG--NH2 by UV-visible spectrophotometry and fluorescence spectrophotometry,respec- tively. Meanwhile,the adsorbed amount of DOX on the ND--PEG--FA nanoparticles is （47 ± 1.26） μg/ mg. Rat C6 glioma cells as in vitro tumor cells model, the uptake of ND-- PEG-- FA/DOX nanoparticles byC6 cells was detected with free folic acid as a competitive agent via flow cytometry showed that the uptake of ND--PEG--FA/DOX nanoparticles was obviously inhibited tion of free FA increasing,and the maximum inhibition rate was 66.13%. It indicated th DOX nanoparticles can be internalized by the C6 cells through folic acid receptor-medi addition,it implies that the ND--PEG--FA nanocarrier has a good ability of targeting d peutics drug. （FCM）. The result with the concentra- at ND-- PEG-- FA/ ated endocytosis. In elivery chemothera-

关 键 词：纳米钻石 聚乙二醇二胺 叶酸 阿霉素 靶向性 

分 类 号：O635[理学—高分子化学] TQ316.4[理学—化学]