Magnetic Hyperthermia Combined With Modulating Oxidative Stress In Tumor Tissue To Amplify Photodynamic Therapy And Inhibit Tumor Metastasis

At present,the treatment methods for tumors mainly include chemotherapy,radiotherapy and surgical resection,but there are disadvantages such as high toxic side effects and high risks,which greatly reduce the therapeutic effect.With further research on tumor treatment,it is found that nano-drug delivery system plays a pivotal role in tumor treatment.Nano-drug delivery systems can be combined with multiple treatment modalities to perform multiple treatments on tumor sites to achieve better therapeutic effects.Among them,photodynamic（PDT）therapy is that photosensitizers generate reactive oxygen（ROS）species under laser irradiation,and reactive oxygen species have a killing effect on tumor tissue.However,the presence of glutathione（GSH）at the tumor site will lead to a decrease in the level of reactive oxygen species and thus affect the therapeutic effect.Dopamine（PDA）is an FDA-approved material with good biocompatibility.At the same time,studies have found that dopamine can consume glutathione to regulate oxidative stress in tumor tissue and allow higher levels of reactive oxygen species to participate in tumor treatment.Dopamine can generate heat under laser irradiation for thermal ablation of tumors,and photothermal-induced immunogenic death can inhibit tumor metastasis.For the treatment of deep tumors,magnetocaloric has attracted much attention due to its high penetrability.Therefore,a composite system of magneto-thermal combined regulation of oxidative stress in tumor tissue was constructed for the study of tumor therapy and anti-metastasis.We fabricated a nanosystem M-MM@PDA that combines magnetothermal and photothermal and can modulate oxidative stress in tumor tissue to amplify photodynamic therapy.First,the magnetic mesoporous silica was synthesized by the sol-gel method;then the photosensitizer methylene blue（MB）was loaded into the nanocarrier M-MM;finally,the final nanocomposite M-MM@PDA was obtained by stirring dopamine and the nanocarrier together.The successful synthesis of M-MM@PDA was proved by TEM,DLS,FTIR,Mapping,etc.The particle size is about 150 nm,the dispersion is good,and the drug loading rate is 28.3%.At the cellular level,it has a good effect of depleting glutathione and the ability to increase the level of ROS.The CCK-8,live and dead cell staining,and flow cytometry experiments proved that M-MM@PDA has a good cell killing effect.Cell migration and invasion experiments also showed that the treatment group could well reduce the migration and invasion abilities of cells compared with the blank group.In vivo fluorescence imaging,magnetic resonance imaging and photothermal imaging in mice confirmed that M-MM@PDA could effectively accumulate at tumor sites;subcutaneous tumor model confirmed that the final treatment group of M-MM@PDA had better performance than other groups Anti-tumor effect and good biosafety;the mouse breast pad orthotopic tumor model confirmed that the final treatment group of M-MM@PDA could well inhibit the growth and metastasis of deep tumors to achieve better therapeutic effect.Our fingings show that the M-MM@PDA nanocomposite has a good effect of depleting glutathione to amplify the effect of photodynamic therapy,and can treat deep tumors and inhibit tumor metastasis under the combination of photothermal and magnetothermal,has a good prospect in the field of tumor therapy.