Magnesium peroxide-based biomimetic nanoigniter degrades extracellular matrix to awake T cell-mediated cancer immunotherapy

As the elite force of our immune system, T cells play a determining role in the effectiveness of cancer immunotherapy. However, the clever tumor cells construct a strong immunosuppressive tumor microenvironment (TME) fortress to resist the attack of T cells. Herein, a magnesium peroxide (MP)-based biomimetic nanoigniter loaded with doxorubicin (DOX) and metformin (MET) is rationally designed (D/M-MP@LM) to awake T cell-mediated cancer immunotherapy via comprehensively destroying the strong TME fortress. The nanoigniter not only effectively initiate CD8+ T cell-mediated immune response by promoting the presentation of tumor antigens, but also greatly facilitate the infiltration of T cells by degrading rigid extracellular matrix (ECM). More importantly, the nanoigniter significantly augment the effector functions of infiltrated CD8+ T cells by Mg2+-mediated metalloimmunotherapy and avoid the exhaustion of CD8+ T cells by improving the acidic TME. Thus, the nanoigniter comprehensively awakes T cells and achieves remarkable tumor inhibition efficacy. [Display omitted] •Build a biomimetic nanoigniter (D/M-MP@LM) by developing co-spraying technology.•MP NP ignites “cold” TME and augments the effector functions of CD8+ T cells.•The combination of DOX and MET degrades ECM to facilitate CD8+ T cell infiltration.•With enhanced T cell infiltration and activation, effectively eliminates tumors.