Immuno-Activated Bacterial-Based Nanoenzymes For Enhanced Radioimmunotherapy

The efficacy of external radiotherapy is often greatly reduced because of the lack of oxygen at the tumor site,and as a local therapy,the immune effect caused by external radiotherapy only produces distant effects in a very small number of individuals.Therefore,how to improve the efficacy of radiotherapy and increase its inhibition of metastatic tumors has potential research value.Nano-enzyme shows a good application prospect in tumor therapy and microenvironment regulation because of its high catalytic activity,stability and low cost.At the same time,as a natural immune stimulator,bacterial carrier has the inherent advantage of being a therapeutic agent or carrier in tumor immunotherapy.Based on this,gold-platinum bimetallic nanoenzyme(Au-Pt)was grown in situ on the surface of attenuated Salmonella typhimurium(VNP20009)by one-step reduction method,and a bacterial-based nanoenzyme carrier(Au-Pt@VNP20009,APV)with high catalase activity was constructed.In order to further enhance the enrichme nt of APV in the tumor site,we use low-dose X-ray to promote tumor site inflammation,and then effectively assist in the delivery of APV by means of monocyte endocytosis and inflammatory tendency of bacterial carriers.On the one hand,APV delivered to th e tumor site can continuously and efficiently catalyze the decomposition of hydrogen peroxide to produce oxygen,improve the tumor hypoxic microenvironment,and relieve the oxygen dependence of subsequent radiotherapy;on the other hand,APV can also promo te the polarization of M1 macrophages and the maturation of DC cells,and regulate the tumor immunosuppressive microenvironment.After combined radioimmunotherapy,cGAS-STING pathway and anti-tumor immune response can be better activated,and tumor growth and metastasis can be effectively inhibited.In a word,this paper combines bimetallic nano-enzyme with bacterial carrier through a simple method,skillfully uses monocytes as a carrier to deliver APV to the tumor site and regulates the tumor anoxic microe nvironment and immune microenvironment,which effectively improves the efficacy of radiotherapy and increases the inhibition of metastatic tumor by radioimmunotherapy.