Application Of Hollow Mesoporous Prussian Blue Loaded Manganese Tetroxide As Radiosensitizer In Radiotherapy Of Hepatocellular Carcinoma

Radiotherapy is one of the treatment methods for advanced liver cancer,but tumor hypoxia microenvironment can cause tumor cells to be insensitive to radiation and reduce the efficacy of radiotherapy.Nano-radiosensitizer has the characteristics of good biosafety,low toxicity and long circulation time,and can improve the local therapeutic effect of tumor at relatively low and safe radiation dose.In this study,we developed a novel nanocomposite（HMPB@Mn₃O₄）as a nano-radiosensitizer through hollow mesoporous Prussian blue（HMPB）loaded with manganese tetroxide（Mn₃O₄）.Based on the excellent catalytic oxygen production activity of the nano-radiosensitizer,the tumor hypoxia was effectively overcome and the synergistic radiosensitization effect was achieved.Studies have shown that the combination of nano-radiosensitizer HMPB@Mn₃O₄and X-ray on human hepatocellular carcinoma cell line 7721 can consume high concentration of reduced glutathione（GSH）in tumor microenvironment,trigger excessive production of intracellular ROS,induce mitochondrial damage and cause apoptosis,thus greatly enhance the anticancer effect.At the same time,HMPB@Mn₃O₄combined with X-ray can also block the cell cycle G2/M and improve the sensitivity of tumor cells to radiotherapy.Further studies on the subcutaneous tumor model of tumor-bearing mice show that the combination of HMPB@Mn₃O₄and X-ray can significantly inhibit the growth of tumor in vivo.At the same time,as a potential Magnetic Resonance Imaging（MRI）contrast agent,HMPB@Mn₃O₄can effectively reduce the T1WI value of tumor tissue and image the tumor,which provides a good guidance for radiotherapy.To sum up,this study provides a strategy for the clinical application of nano-radiosensitizers in tumor radiosensitization.