Objective To investigate the mechanism and effect of nanocomposites(SFB@MOF-Fc)loaded with sorafenib(SFB)to reverse tumor drug resistance.Methods The construction of SFB-resistant tumor cell model and the study of resistance mechanism were investigated by flow cytometry and cell viability.The in vitro anti-tumor ability of drug-carrying nanoplatforms was investigated by cell viability and 3D tumor sphere cell live/dead staining analysis.The in vitro anti-tumor mechanism of drug-carrying nanoplatforms was investigated by the detection of the level of intracellular reactive oxygen species(ROS)and by bioelectron microscopy study.Results SFB-resistant cells(Huh7-SR)showed successful establishment by the cell viability analysis.The analysis of ROS levels in Huh7 cells as well as Huh7-SR cells detected by the flow cytometry showed that ROS levels in Huh7-SR were insignificantly elevation after SFB drug treatment,suggesting that ROS levels may influence resistance mechanisms.The analysis of cell viability as well as 3D tumorsphere cell live/dead staining showed that the cell viability as well as cell death fluorescence were greatly increased after SFB@MOF-Fc treatment,indicating the SFB@MOF-Fc successfully reversed drug resistance in the in vitro model.ROS levels as well as bioelectron microscopy analyses showed that SFB@MOF-Fc composite nanomaterials could reverse the tumor resistance through a mechanism that enhances the production of iron death in Huh7-SR cells and amplifies the level of oxidative stress.Conclusion After SFB@MOF-Fc is endocytosed by tumor cells,the drug uptake in cells increased.The oxidative stress levels were amplified through intracellular ferroptosis,and successfully reversed the drug resistance of tumor cells.
NETL
NSTL
万方数据
