Abstract
The therapeutic efficacy of radioimmunotherapy against triple negative breast cancer (TNBC) is largely limited by the complicated tumor microenvironment (TME) and its immunosuppressive state. Thus developing a strategy to reshape TME is expected to achieve highly efficient radioimmunotherapy. Therefore, we designed and synthesized a tellurium (Te)-driven maple leaf manganese carbonate nanotherapeutics (MnCO(3)@Te) by gas diffusion method, but also provided a chemical catalytic strategy in situ to augment ROS level and activate immune cells for improving cancer radioimmunotherapy. As expected, with the help of H(2)O(2) in TEM, MnCO(3)@Te heterostructure with reversible Mn(3+)/Mn(2+) transition could catalyze the intracellular ROS overproduction to amplify radiotherapy. In addition, by virtue of the ability to scavenge H(+) in TME by carbonate group, MnCO(3)@Te directly promote the maturation of dendritic cells and macrophage M1 repolarization by stimulator of interferon genes (STING) pathway activation, resulting in remodeling immuno-microenvironment. As a result, MnCO(3)@Te synergized with radiotherapy and immune checkpoint blockade therapy effectively inhibited the breast cancer growth and lung metastasis in vivo. Collectively, these findings indicate that MnCO(3)@Te as an agonist, successfully overcome radioresistance and awaken immune systems, showing promising potential for solid tumor radioimmunotherapy.