To investigate the mechanism and effect of porous hollow iron oxide nanoparticles (HION) nanosensitizers (HION/VER) loaded with VER-155008 prepared to enhance the radiofrequency ablation on hepatocellular carcinoma tumors.

The construction of porous hollow iron oxide nanosensitizers and drug loading were investigated by transmission electron microscopy and zeta potential experiments. The in vitro anti-tumor ability of the sensitizers was examined by cell viability and cell live/dead staining experiments. The in vitro anti-tumor mechanism of the sensitizers was investigated by measuring the intracellular levels of reactive oxygen species (ROS), glutathione (GSH) and heat shock protein 70 (HSP70).

Through material characterization analysis, porous hollow iron oxide nanosensitizers have been successfully constructed with a particle size of about 100 nm. HION/VER reduced tumor cell survival to 50% at 56.89 μg/mL and 45℃. Live/dead staining assay further confirmed that a large number of tumor cells died, indicating that HION/VER has good anti-tumor ability in vitro. Analysis by reactive oxygen fluorescence probe and glutathione level showed that reactive oxygen fluorescence was significantly enhanced and GSH levels decreased, indicating that HION/VER nano-sensitizer could promote iron death through the mechanism of disrupting redox balance. Analyzed by HSP70 immunofluorescence assay, the cellular HSP70 expression was significantly reduced after HION/VER treatment, indicating that the nano-sensitizer increased the sensitivity of tumor cells to mild radiofrequency ablation by inhibiting HSP70.

After HION/VER was endocytosed by the tumor cells, the drug uptake in the cells was increased, and the inhibition of HSP70 increased the sensitivity of the tumor cells to mild radiofrequency ablation by disrupting the redox balance to enhance the iron death, and the effect of radiofrequency ablation was achieved by effectively increasing the sensitivity of the tumor cells to mild radiofrequency ablation.