Motif-designed peptide nanosheets with AuNBP@PtS nanozymes enable multimodal breast cancer therapy via enhanced photothermal and chemodynamic effects.
Background
Current breast cancer therapies often face challenges like limited efficacy, systemic toxicity, and drug resistance, necessitating innovative approaches. Nanozyme-based biocomposites offer a promising avenue by leveraging their catalytic activity to modulate the tumor microenvironment and enhance therapeutic outcomes. However, developing biocompatible and structurally defined nanoplatforms that integrate multiple therapeutic modalities remains a significant gap. This study addresses this by engineering a peptide-directed nanozyme system to achieve synergistic photothermal and chemodynamic therapy.
Study Design
Researchers engineered core-shell bimetallic nanozymes onto two-dimensional (2D) peptide biomatrices. A motif-designed peptide, Fmoc-FKKGSHC, was self-assembled into uniform peptide nanosheets (PNSs), serving as bioactive scaffolds. Gold nanobipyramids coated with platinum shells (AuNBP@PtS) were then incorporated to create organic-inorganic biocomposites, PNS/AuNBP@PtS. The AuNBP cores were activated by near-infrared irradiation for photothermal conversion, while the PtS shells catalyzed hydrogen peroxide decomposition. The therapeutic efficacy and safety were evaluated through in vitro and in vivo studies, assessing tumor ablation and systemic toxicity.
Results
The engineered PNS/AuNBP@PtS biocomposites demonstrated excellent biocompatibility and synergistic therapeutic performance. The AuNBP cores provided strong localized surface plasmon resonance, leading to sharp-tip-enhanced photothermal conversion under near-infrared irradiation. Concurrently, the PtS shells effectively catalyzed the decomposition of hydrogen peroxide to generate highly reactive hydroxyl radicals. This dual mechanism synergistically induced localized hyperthermia, disrupted mitochondrial integrity, and amplified oxidative stress within tumor cells. > In both in vitro and in vivo evaluations, the PNS/AuNBP@PtS system achieved efficient tumor ablation. Crucially, these therapeutic effects were observed with negligible systemic toxicity and no evident histopathological damage to major organs, highlighting a favorable safety profile for this multimodal approach.
Key Findings
- Motif-designed peptide
Fmoc-FKKGSHCself-assembled into uniform peptide nanosheets (PNSs). - PNSs served as scaffolds for
AuNBP@PtSnanozyme incorporation, formingPNS/AuNBP@PtSbiocomposites. AuNBPcores enabled photothermal conversion undernear-infrared irradiation.PtSshells catalyzedhydrogen peroxidedecomposition intohydroxyl radicalsfor chemodynamic therapy.- The biocomposites achieved efficient tumor ablation
in vitroandin vivowith negligible systemic toxicity.
Why It Matters
This work establishes a novel biomimetic peptide-directed nanozyme self-assembly strategy, offering a versatile platform for multimodal cancer therapy. The integration of photothermal and chemodynamic therapies into a single, biocompatible peptide-based nanoplatform could significantly improve treatment efficacy while reducing systemic side effects. For future clinical translation, this approach suggests a pathway for developing more targeted and less invasive cancer treatments. While still in preclinical stages, the demonstrated safety and efficacy in vivo pave the way for further optimization and potential application in human breast cancer protocols, potentially enabling more precise tumor ablation with minimal collateral damage.
breast cancer
nanozyme
peptide
photothermal therapy
chemodynamic therapy
preclinical-animal