Inspired by Game Theory: Glutathione-induced in Situ Michael Addition between Nanoparticles for Pyroptosis and Immunotherapy.

Abstract

As its complexity and genetic instability, 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. Here, we prepare biomineralized oxidized (-)-epigallocatechin-3-o-gallate (EGCG)-molybdenum ion coordination nanoparticles for disrupting redox equilibrium and simultaneously reacting with intracellular GSH via Michael addition to form large aggregations that can mechanically disrupt endosomal and plasma membrane, 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, gaining optimal payoff in competition and cooperation in cancer therapy.