功能化氧化石墨烯作为基因和抗肿瘤药物纳米载体的制备及性能研究  

Preparation and characterization of functional graphene oxide as nanocarriers for genes and anti-tumor drugs

作　　者：曹秀芬[1] 冯福立[1] 杨晓英[1] 周晶[1] 

机构地区：[1]天津医科大学药学院天津市临床药物治疗和诊断重点实验室,天津300070

出　　处：《天津医科大学学报》2013年第3期178-181,259,共5页Journal of Tianjin Medical University

基　　金：国家自然科学基金资助项目(51103106)

摘　　要：目的:制备乳糖酰化壳聚糖修饰的氧化石墨烯季铵盐(GO-LCO+),作为基因和抗肿瘤药物载体。方法:采用EDC/NHS催化法制备乳糖酰化壳聚糖,并连接到氧化石墨烯(GO)上,再用2,3-环氧丙基三甲基氯化铵将其季铵化,制备GO-LCO+。采用红外光谱(IR)、电位及纳米粒度分析仪、原子力显微镜(AFM)等方法对GO-LCO+的结构和形态进行表征。然后通过非共价键将抗肿瘤药盐酸阿霉素(DOX)负载到载体上,紫外光谱仪(UV)测定负载量。通过静电作用负载荧光素标记的DNA(FAM-DNA),琼脂糖凝胶电泳测定负载量,共聚焦荧光显微镜观察人肝癌细胞(QGY-7703)对GO-LCO+/FAM-DNA的摄取情况,最后采用WST-1试验对GO-LCO+的细胞毒性进行了测定。结果:IR、AFM、Zeta电位数据显示成功制备GO-LCO+,UV检测载体对DOX的负载量为477μg/mg,电泳试验检测载体对FAM-DNA的负载量是4μmol/g,激光共聚焦荧光显微镜下观察GO-LCO+可快速运载FAM-DNA到达细胞内,WST-1试验显示载体对细胞基本没有毒性。结论:GO-LCO+作为基因和抗肿瘤药物载体,具有优良的载药性能和较低的细胞毒性。Objective： To prepare lactose acylated chitosan modified graphene oxide quaternary ammonium salt （GO-LCO^＋） as nanocar- tiers for genes and anti-tumor drugs. Methods： First, lactose acylated chitosan was prepared via EDC/NHS catalytic method, then linked it to graphene oxide （GO）, finally lactose acylated ehitosan modified graphene oxide quaternary ammonium salt （GO-LCO^＋） were prepared with 2, 3-epoxypropyl trimethyl ammonium chloride. Infrared spectroscopy （IR）, laser particle size analyzer and atomic force microscope （AFM） were used to characterize the structure and morphology. The anti-tumor drugs doxorubicin choloride （DOX） was loaded onto the carrier via noncovalent bonding and loading capacity was detected by ultraviolet spectrograph （UV）. Then fluoreseein FAM-labeled DNA （FAM-DNA） was loaded onto it through the electrostatic interaction and loading capacity was detected via electrophoresis test. The up- take of GO-LCO^＋/FAM-DNA by hepatic tumor cells （QGY-7703） were observed by confocal laser scanning fluorescence microscopy. Fi- nally, the eytotoxicity of this carrier was determined through WST- 1 test. Results： IR, AFM, Zeta-potential records showed that GO- LCO^＋ were prepared successfully. The loading capacity of DOX was 477 μg/mg. The loading capacity of FAM-DNA was 4μmol/g. GO- LCO^＋ loading FAM-DNA could fast uptake by QGY-7703. No obvious toxicity was observed by WST-1 test. Conclusion： GO-LCO^＋ used in genes and anti-tumor drugs carrier are prepared successfully, which have good loading function and lower eytotoxicity.

关 键 词：氧化石墨烯 药物载体 负载量 细胞毒性 

分 类 号：R9[医药卫生—药学]