Zinc Ferrite Magnetic Nanomaterials Induce Reactive Oxygen Species And Pro-death Autophagy To Kill Renal Cancer Cells

Objective: To investigate the killing effect of zinc magnetic ferrite nanomaterials(ZFNPs)on kidney cancer Caki-1 cells and its correlation with ROS and autophagy.Methods: ZFNPs were synthesized by aqueous method and characterized by TEM and other methods.The inhibitory effect of ZFNPs on Caki-1 cells was detected by Thiazole Blue(MTT)assay.Intracellular ROS levels were detected by DCFH-DA staining.TEM was used to observe the autophagosomes in Caki-1 cells after ZFNPs treatment.The changes of autophagy effect were detected by Western blot.DCFH-DA staining,MTT and Western blot were used to explore the modulatory mechanism between ROS and autophagy in the tumoricidal effect of ZFNPs in Caki-1 cells.Results: ZFNPs with uniform size and shape were synthesized by aqueous method,which exerts paramagnetic properties for MRI.ZFNPs had a dose and time dependent killing effect on Caki-1 cells.In this process,ZFNPs could induce Caki-1 cells to produce dose and time dependent ROS,while NAC could reduce the production of ROS and weaken the killing effect of ZFNPs.ZFNPs could also elicit autophagy in Caki-1cells.After co-treatment with Wortmannin,the accumulation of LC3-II decreased and the subsequent cell viability was higher than that of ZFNPs treated alone,while co-treatment with Trehalose could increase ROS production and autophagic intensity in executing tumoricidal effect of ZFNPs.Among the sensitization process,NAC could reduce the accumulation of LC3-II and Wortmannin could decrease ROS generation.Conclusions: ZFNPs have the potential to become a MRI contrast agent,and can induce ROS and pro-death autophagy to kill Caki-1 cells,which may play an important role in renal cancer theranosis.