多柔比星-TiO_2纳米粒克服肿瘤多药耐药的研究  

Overcoming Cancer Multidrug Resistance by Doxorubicin-TiO_2 Nanoparticles

作　　者：李天傲[1,2] 杨建苗 许东航[2] 高建青[4] LI Tian-ao;YANG Jian-miao;XU Dong-hang;GAO Jian-qing(Chinese Pharmaceutical Association,Beijing 100022,China;Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China;Taizhou Hospital of Zhejiang Province,Taizhou Enze Medical Center（Group）,Zhejiang Taizhou 317000,China;Institute of Pharmaceutics,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]中国药学会,北京100022 [2]浙江大学医学院附属第二医院,杭州310009 [3]台州恩泽医疗中心(集团)浙江省台州医院,浙江台州317000 [4]浙江大学,杭州310058

出　　处：《中国药学杂志》2018年第14期1198-1202,共5页Chinese Pharmaceutical Journal

基　　金：浙江省自然科学基金项目资助(LY18H300004;LY15H300001);台州市科技计划项目资助(1801ky04)

摘　　要：目的探讨多柔比星-TiO_2纳米粒克服肿瘤多药耐药作用。方法以人白血细胞系K562/DOX耐药细胞为模型细胞,多柔比星溶液和多柔比星脂质体为对照,MTT法测定多柔比星-TiO_2纳米粒的细胞毒性,HPLC测定不同时间点耐药细胞中药物量以分析细胞摄取和细胞外排行为,并用流式细胞仪测定P-gp表达以探讨其克服MDR可能机制。结果多柔比星-TiO_2纳米粒组IC50较多柔比星溶液组明显下降;细胞摄取实验显示,多柔比星-TiO_2纳米粒组经4 h孵育后耐药细胞K562/DOX内的药物量是多柔比星脂质体的1.23倍,细胞外排实验显示,多柔比星-TiO_2纳米粒组进入耐药细胞的药物量是多柔比星脂质体的1.18倍,均远高于多柔比星溶液组;P-gp表达实验显示,多柔比星-TiO_2纳米粒与多柔比星脂质体具有相似的下调P-gp表达作用。结论多柔比星-TiO_2纳米粒具有克服肿瘤多药耐药作用,TiO_2纳米粒可能是克服肿瘤多药耐药作用的新型无机纳米载体。OBJECTIVE To investigate the effect of TiO2 nanoparticles on overcoming cancer muhidrug resistance （ MDR）. METHODS Doxorubicin-TiO2 nanoparticles（DTN） were prepared, the K562/DOX cells were chosen as the model cells. And doxo- rubicin solution（F-DOX） and doxorubicin liposomes（DOX-L） were also prepared as the control. The MTT assay were measured, and the amount of doxorubicin in the K562/DOX cells at different time were determined by HPLC. The P-gp expression were detected by flow cytometry. RESULTS The MTT assay shows that IC50 of group DTN were lower than that of group F-DOX. The uptake test shows that amount of doxorubicin in K562/DOX cells of group DTN was 1.23 times of group DOX-L when in 4 h, and the efflux test shows that amount of doxorubicin in K562/DOX cells was 1. 18 times of group DOX-L. The flow cytometry result revealed that the effect of TiO2 nanoparticles on overcoming MDR maybe through down-regulating the expression of P-gp in K562/DOX cells. CONCLUSION The TiO2 nanoparticles are a new inorganic materials-based nanoparticles which promising approach to overcome MDR.

关 键 词：多柔比星 TiO2纳米粒 多药耐药 积聚 机制 肿瘤 

分 类 号：R969.1[医药卫生—药理学]