Glutathione-Induced In Situ Michael Addition between Nanoparticles for Pyroptosis and Immunotherapy

Most tumor treatments will fail when ignoring competition and cooperation between each cancer cell and its microenvironment. Inspired by game theory, therapeutic agents can be introduced to compete for intracellular molecules to disrupt the cooperation between molecules and cells. Biomineralized oxidized (-)-epigallocatechin-3-o-gallate (EGCG)-molybdenum ion coordination nanoparticles were prepared for disrupting redox equilibria and simultaneously reacting with intracellular GSH in a Michael addition to form large aggregates that can mechanically disrupt endosomal and plasma membranes, stimulating pyroptosis and anti-tumor immunological responses for versatile inhibition of different types of tumors. This design disrupts the cooperation between molecules and between cancer and immune cells, achieving an optimal payoff in competition and cooperation in cancer therapy.