A glutathione responsive nanoplatform made of reduced graphene oxide and MnO₂ nanoparticles for photothermal and chemodynamic combined therapy

Based on the specific tumor microenvironment, characterized by an overproduction of H₂O₂ and a high glutathione (GSH) concentration, the cascade reactions of nanomaterials, capable of mediating GSH depletion and reactive oxygen species (ROS) generation, have become a popular strategy to increase cancer therapy efficiency. In this study, we exploited reduced graphene oxide (rGO), one of the most promising graphene-based materials, in combination with manganese dioxide nanoparticles (MnO₂ NPs) to design a multifunctional nanoplatform (rGO@MnO₂) for efficient photothermal/chemodynamic combined therapies. MnO₂ NPs were anchored onto the surface of rGO nanosheets (rGO NSs). MnO₂ NPs oxidize intracellular GSH, and the generated Mn²⁺ ions converted H₂O₂ into HO[rad] by Fenton reaction. Meanwhile, rGO NSs mediated photothermal therapy (PTT) could further kill cancer cells. High temperature caused by photothermal conversion increased Fenton reaction rate, which enhanced the efficiency of MnO₂ NPs mediated chemodynamic therapy (CDT). Importantly, thanks to the enhanced cell uptake of MnO₂ NPs favored by the delivery properties of rGO, rGO@MnO₂ possessed higher lethality to cancer cells. The decrease in the nanomaterials’ effective dose would further improve biosecurity and reduce cost. Therefore, rGO@MnO₂ have great potential in cancer therapy by exploiting the synergistic effect of PTT and photothermal/delivery effect enhanced CDT.