A CuS/Ag/Pt@ICG/DOX nanoplatform with cascaded nanozyme catalysis for tumor microenvironment remodeling and synergistic photodynamic/photothermal/chemodynamic therapy.

This work introduces the rational design of a hierarchically structured, multi-enzyme integrated therapeutic platform, referred to as HCuS/Ag/Pt/ICG/DOX (CAPID). The platform is constructed by depositing dual-enzyme-active Ag/Pt on copper sulfide nanoparticles (CuS NPs) to remodel the tumor microenvironment (TME), followed by loading indocyanine green (ICG) as a near-infrared (NIR) fluorophore and doxorubicin (DOX) as a chemotherapeutic payload. The CAPID platform utilizes catalase to decompose H2O2 into oxygen (O2), which synergizes with endogenous H2O2 to initiate a Fenton-like reaction, generating cytotoxic hydroxyl radicals (·OH). The redox cycling between Cu2 + ions and intracellular thiols depletes GSH, amplifying oxidative stress cascades. NIR irradiation achieved 88.9 % tumor inhibition via spatiotemporal tri-therapy (chemo/PDT/PTT) synergy, thereby addressing the limitations of monotherapy through nanoplatform engineering.