Bio-camouflaged nanoreactors with spatiotemporally controlled Cu2+-Fenton catalysis for enhanced starvation-augmented mild photothermal therapy
Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to its high invasiveness and adaptive resistance. We report a bio-mimetic nanoplatform (HMPB-GOx@HSA-Cu2+) integrating starvation therapy, Fenton/Fenton-like catalysis, and mild photothermal therapy (mPTT) for synergistic TNBC treatment. The nanoreactor comprises a hollow mesoporous Prussian blue (HMPB) core loaded with glucose oxidase (GOx), encapsulated in a human serum albumin (HSA) shell covalently functionalized with Cu2+ ions. This design enables spatiotemporal control of Cu2+-mediated Fenton catalysis, responding to the tumor microenvironment (TME) to generate cytotoxic hydroxyl radicals (·OH). GOx catalyzes glucose depletion, elevating H2O2 levels and acidity, thereby enhancing catalytic efficiency. Concurrently, mPTT at ~43–45°C accelerates the Fenton reaction and suppresses heat shock protein (HSP) expression, overcoming thermal tolerance via ATP depletion. In vitro and in vivo studies demonstrate significant anti-tumor efficacy through reactive oxygen species (ROS) accumulation and metabolic disruption, with excellent biocompatibility. This work presents a highly integrated strategy for precise TNBC therapy, addressing limitations of conventional monotherapies.