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

Abstract

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.

Keywords: Biomimetic nanomedicine; Cancer therapy; Magnesium peroxide; Metalloimmunotherapy; Tumor microenvironment.