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

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.