阴离子调控PEG化纳米钻石对阿霉素的负载及其与HepG2肿瘤细胞的作用  

Loading of Doxorubicin by Anion-Regulated PEGylated Nanodiamond and Its Effect on HePG2 Tumor Cells

作　　者：魏仕国 杜祥斌 焦卫卫 李英奇[1] WEI Shiguo;DU Xiangbin;JIAO Weiwei;LI Yingqi(School of Chemistry and Chemical Engineering,Shanxi University,Taiyuan 030006,China)

机构地区：[1]山西大学化学化工学院,山西太原030006

出　　处：《山西大学学报（自然科学版）》2020年第2期368-376,共9页Journal of Shanxi University(Natural Science Edition)

基　　金：中央引导地方科技发展专项资金项目(YDZX20191400002477);山西省重点研发计划项目(201903D321105);山西省“1331工程”(2018-CT-1)。

摘　　要：纳米钻石(ND)因具有高生物相容性、高化学稳定性、对生物分子和药物高亲和力以及表面易于修饰等优点,使其在生物医药方面的应用备受关注。文章采用共价耦联方法,用NH2-PEG-COOH(PEG)修饰ND形成PEG化纳米钻石(ND-PEG),使其作为药物载体,分别探究了在浓度为1 mol/L的Ac^-、Cit^3-和HCO^-3介质中物理吸附抗癌药物阿霉素(DOX)的影响。发现ND-PEG对DOX吸附量的大小顺序为Ac^->HCO-^3>Cit^3-,且远大于在去离子水中的吸附量,表明ND-PEG吸附DOX受阴离子调控。在Na3Cit介质中负载DOX的量为125.24μg/mg,体外模拟释药表明在pH 5.0时体系的累积释药率为34.83%,其药物利用率最高。利用紫外可见分光光度计、傅里叶红外光谱仪和马尔文粒度仪对纳米粒子进行了表征。此外,通过细胞形态和MTT实验探究了该纳米药物体系与人肝癌细胞(HepG2)的作用,显示ND-PEG/DOX能高效杀死肿瘤细胞,这为制备高载药量的纳米钻石药物体系奠定了实验基础。Nanodiamond(ND)has attracted much attention in biomedical applications due to its advantages of high biocompatibility,high chemical stability,high affinity for biomolecules and drugs,and easy surface modification.ND was covalently coupled with H2N-PEG-COOH(PEG)to form PEGylated ND(ND-PEG),which was used as a drug carrier to investigate the effect on physical adsorption of anticancer drug doxorubicin(DOX)in Ac^-,Cit^3-and HCO^-3 media with a concentration of 1 mol/L,respectively.It was found that the order of DOX adsorption amount was Ac^->HCO^-3>Cit^3-,and the adsorption amount was much higher than that in deionized water,indicating that ND-PEG adsorbing DOX was regulated by anions.The DOX adsorption amount in Na3Cit was 125.24μg/mg,and the in vitro simulated release showed that the cumulative release rate of ND-PEG/DOX system was 34.83%,which has the highest drug utilization rate.The nanoparticles were characterized by UV-vis spectrophotometer,Fourier infrared spectrometer and Zetasizer Nano.In addition,the effect of ND-PEG/DOX on human hepatoma cells(HepG2)was investigated by cell morphology and MTT assay,which displayed that ND-PEG/DOX could effectively kill tumor cells.It laid an experimental foundation for the preparation of ND drug system with high drug load.

关 键 词：纳米钻石 阿霉素 阴离子调控 高药物负载 

分 类 号：R96[医药卫生—药理学]