Necroptosis-elicited host immunity: GOx-loaded MoS₂ nanocatalysts for self-amplified chemodynamic immunotherapy

Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness. However, revealing the pathway of how nanoagents themselves trigger the host immunity or how to maximize the immunotherapy efficacy still needs further exploration. Herein, rose-like MoS₂ nanoflowers modified with 2-deoxy-D-glucose (2-DG) and glucose oxidase (GOx) (MPGGFs) have been successfully fabricated via a one-pot hydrothermal reaction and following one-by-one surface modification as a multifunctional nanocatalyst for photothermal therapy enhanced self-amplified chemodynamic immunotherapy (PTT-co-CDT). By introducing GOx, the obtained MPGGFs exhibited self-amplified chemodynamic therapeutic efficacy under hypoxia tumor microenvironment (TME) because of the raised intracellular H₂O₂ level via enzyme-catalysis of oxygen. Furthermore, combined with the intrinsic excellent photothermal conversion efficiency of MoS₂ nanoflowers, PTT-co-CDT performances by MPGGFs could effectively induce the necroptosis of tumor cells both in vitro and in vivo. Then the induced necroptosis via PTT-co-CDT by MPGGFs could directly trigger host immunity by activating the antigen-specific T-cells (CD4⁺ and CD8⁺). Finally, the excellent in vivo safety of MPGGFs makes us believe that the successful construction of rose-like multifunctional nanocatalyst not only has great potentials for self-amplified chemodynamic immunotherapy, but also provides a paradigm for exploring necroptosis triggered host immunity for cancer treatment.