Hierarchical collective spin polarization enhances cancer chemodynamic therapy

Chemodynamic therapy (CDT) relies on Fenton-like catalysis to convert endogenous H₂O₂ into cytotoxic reactive oxygen species (ROS). However, its efficacy is limited by the sluggish catalytic kinetics under physiological conditions. Here we report a multifunctional nanoplatform that integrates Fenton-like catalysis with spin-dependent electronic structure modulation, glutathione (GSH) depletion, and photothermal conversion. Compared with single-atom Co sites, Co nanoparticles exhibiting collective spin polarization display enhanced catalytic activity toward hydrogen peroxide (H₂O₂), resulting in more efficient generation of hydroxyl radicals (·OH). Theoretical calculations indicate that collective spin polarization modulates the electronic structure of Co, facilitating the adsorption and activation of intermediates and accelerating the catalytic reaction kinetics. Additionally, Cu species are introduced to deplete intracellular GSH, thereby reducing the scavenging of ROS. Y6 loading enhances photothermal conversion efficiency, further potentiating tumor inhibition, while the resulting hyperthermia also promotes the catalytic process. Both in vitro and in vivo studies confirm the effective tumor suppression. These findings demonstrate that spin-dependent electronic structure engineering provides a promising strategy to enhance the therapeutic efficacy of CDT.