Engineering sharp-tip bimetallic nanozymes onto motif-designed two-dimensional peptide biomatrices for multimodal breast Cancer therapy.

Nanozyme-based biocomposites have emerged as versatile biomedical platforms owing to their ability to catalyze reactive species, modulate the tumor microenvironment, and enhance therapeutic efficacy. In this study, core-shell bimetallic nanozymes were rationally engineered on two-dimensional (2D) peptide biomatrices to construct an integrated nanoplatform with excellent biocompatibility and synergistic therapeutic performance. Through controlled peptide self-assembly and edge-to-edge fusion, a motif-designed peptide (Fmoc-FKKGSHC) evolved from disordered clusters into uniform peptide nanosheets (PNSs), which served as structurally defined and bioactive scaffolds for subsequent biocomposite assembly. Gold nanobipyramids coated with platinum shells (AuNBP@PtS) were subsequently incorporated to form 2D organic-inorganic biocomposites (PNS/AuNBP@PtS) integrating photothermal and peroxidase-mimicking functionalities. The AuNBP cores provide strong localized surface plasmon resonance and sharp-tip-enhanced photothermal conversion under near-infrared irradiation, whereas the Pt shells catalyze the decomposition of hydrogen peroxide to generate highly reactive hydroxyl radicals. This synergistic mechanism induces localized hyperthermia, disrupts mitochondrial integrity, and amplifies oxidative stress, thereby enhancing combined photothermal and chemodynamic therapy. The in vitro and in vivo evaluations demonstrate efficient tumor ablation with negligible systemic toxicity and no evident histopathological damage to major organs. Overall, this work establishes a biomimetic peptide-directed nanozyme self-assembly engineering strategy and highlights the potential of peptide-based functional biocomposites as versatile platforms for multimodal cancer therapy.