LSPR-driven interfacial synergy in an Au@Prussian blue heterostructures for potent chemo-photothermal therapy

• A novel Au@PB heterostructure for synergistic multimodal tumor therapy was developed. • LSPR effect of Au NPs boosts photothermal conversion and catalytic activity. • The engineered interface facilitates electron transfer for catalytic stability. • Cascade catalysis enables in situ H 2 O 2 generation for enhanced chemodynamic therapy. Nanozyme-based tumor therapies are hampered by the low catalytic efficiency and limited stability of monometallic nanonzymes, as well as insufficient H 2 O 2 in the tumor microenvironment. Here, we present a heterostructured Au@Prussian blue nanoassembly (Au@PB NPs) synthesized by in situ growth of gold nanoparticles (Au NPs) on Prussian blue nanoparticles (PB NPs), integrating chemodynamic, photothermal, and starvation therapies. The LSPR effect of Au NPs significantly enhances both photothermal conversion and catalytic activity through hot electron transfer. The spatial arrangement enables cascade catalysis, with Au NPs catalyzing glucose oxidation to generate H 2 O 2 , which is efficiently used by PB NPs for Fenton-like hydroxyl radical (•OH) production, amplifying ROS-mediated tumor cell damage. Furthermore, the engineered interface supports bidirectional electron transfer and sustained Fe 2+ regeneration, improving catalytic durability. Both in vitro and in vivo studies demonstrate robust tumor suppression, enhanced ROS generation, efficient GSH depletion, and favorable biocompatibility. This work provides a rational strategy for designing multifunctional nanozymes for synergistic and precise cancer therapy.