Study Of Iridium Phthalocyanine Complex Nanoparticles In Sonodynamic-immunotherapy

Insufficient oxygen supply is common in various solid tumors,which is considered to be one of the characteristics of advanced solid tumors.Hypoxia can promote tumor angiogenesis and cancer metastasis;malignant hypoxia also leads to inherent resistance to drug treatments(such as radiotherapy,chemotherapy,photodynamic therapy,and sonodynamic therapy),thus leading to the failure of many anti-tumor technologies.In recent years,sonodynamic therapy as a minimally invasive non-invasive treatment method has been widely studied for tumor treatment.The corresponding sonosensitizer is activated by US to produce more toxic reactive oxygen species(ROS)for tumor treatment.Compared with photodynamic therapy strategies,SDT offers many advantages,such as deeper penetration depth,less phototoxicity,and fewer side effects.Although preclinical studies of SDT have shown good results in a variety of cancer cells,the therapeutic effect of tumor elimination in vivo is far from satisfactory.Therefore,many new nano-platforms are being applied in this emerging field to solve these inherent obstacles.Among them,the combination of SDT with other treatment strategies is better than single treatment in improving anti-cancer activity.Cancer immunotherapy uses the immune system to trigger an anti-tumor response against malignant tumors.Immune activated anti-tumor immune response can promote systemic immune monitoring,eliminate local and diffuse metastatic tumors,and establish long-term immune memory to prevent tumor recurrence.Animal models have confirmed that tumor cell fragments produced by SDT can be used as a source of tumor antigen to induce host anti-tumor immunity.Therefore,the combination of SDT and immunotherapy can not only effectively treat primary cancer,but also inhibit the recurrence of cancer,so as to improve the efficiency of SDT.IrPc NPs with simulated catalase activity prepared by our research group to explore the therapeutic effect of IrPc NPs on tumor by cell level and 4T1 mouse tumor model under ultrasound.IrPc NPs catalyze endogenous H₂O₂ to produce more oxygen,thus changing the hypoxic environment of tumor cells.On the one hand,the tumor cells with improved hypoxic environment can produce more ROS under the effect of ultrasound,which can improve the efficiency of SDT;on the other hand,the production of oxygen can inhibit the expression of Hif-1?,which can inhibit the growth of tumor to a certain extent.In addition,ROS produced by sonodynamic therapy can cause oxidative stress,lead to immunogenic cell death(ICD),activate the immune system,and realize the combined therapy of sonodynamic and immune.