Modulation of Oxidative Stress in Cancer Cells with a Biomineralized Converter

Oxidative stress modulation is effective to kill cancer. While considerable effort has focused on the promotion of reactive oxygen species (ROS) levels, an additional crucial aspect of ROS regulating systems is the cancer-cell-specific ROS production. Here, we describe a biomineralized nanoparticle that sequentially generates and converts multiple oxygen metabolites into the hydroxyl radical (·OH) in situ in the tumor microenvironment. The biomineralized nanoparticles are MnO₂ mineralized bionanoparticles consisting of epigallocatechin gallate (EGCG) and bovine serum albumin (BSA). Overexpressed glutathione in cancer cells dissolves the MnO₂ outer layer and induces EGCG autoxidation to elevate O₂^–· and H₂O₂ levels. Meanwhile, the generated Mn²⁺ catalyzes the conversion of H₂O₂ into ·OH. In addition, the biomineralized nanoparticles modulate the antioxidant system to circumvent tumor resistance to oxidative stress. Using a xenograft mouse model, the biomineralized converter in situ activates cancer-cell-specific ROS burst and inhibits tumor growth with good biosafety, suggesting great potential for precision cancer therapy.