Hierarchical collective spin polarization enhances cancer chemodynamic therapy

The unique electronic structure of spin-polarized Co nanoparticles enables superior ·OH generation. • Cu-mediated GSH depletion suppresses ROS scavenging and amplifies oxidative damage. • Y6-enabled PTT accelerates catalytic kinetics and induces tumor cell apoptosis. • A combined CDT/PTT nanoplatform achieves effective tumor inhibition. Chemodynamic therapy (CDT) relies on Fenton-like catalysis to convert endogenous H 2 O 2 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 (H 2 O 2 ), 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. Scale modulation from Co single-atom to Co nanoparticles induces collective spin polarization, transforming localized spins into collective spin-polarized state. This spin evolution promotes the adsorption and activation of H 2 O 2 and accelerates Fenton-like ·OH generation. The spin-enabled catalytic enhancement supports more efficient chemodynamic therapy for tumor therapy. Download: Download high-res image (113KB) Download: Download full-size image