1. Journal Source: Advanced Materials


2. Original Title: A Novel pH‑Activatable Nanozyme for Treating Breast Cancer Bone Metastasis by Regulating Cancer Cell Metabolic Reprogramming and the Tumor Microenvironment


3. Research Highlights This work designs a bone-targeted, pH-responsive multi-layer core-shell SPMMPA nanozyme. Combined with multi-omics analysis to characterize oxidative phosphorylation in breast cancer bone metastatic cells, it investigates the regulatory effects of the nanozyme on tumor metabolic reprogramming and the bone microenvironment. Photothermal therapy is integrated to explore the underlying mechanisms at both in vitro and animal levels.


4. Innovations Multi-omics evidence confirms the metabolic feature of upregulated oxidative phosphorylation in breast cancer bone metastatic cells. A Prussian blue‑manganese dioxide heterogeneous interface is constructed to achieve multi-enzyme activities activated by the acidic tumor microenvironment. Bone-targeting peptides and alendronate are integrated to simultaneously interfere with tumor energy metabolism and osteoclast-mediated bone destruction.


5. Material Development (1) Materials: Prussian blue serves as the inner core, disulfide-bond-linked mesoporous silica as the intermediate layer, and manganese dioxide as the outer shell. The surface is modified with PEI, alendronate and SDSSD bone-targeting peptides to obtain the SPMMPA nanozyme. (2) Functions: It exhibits multiple enzyme-mimicking activities including peroxidase-like, oxidase-like and catalase-like activities as well as photothermal effects. It catalyzes reactive oxygen species generation and depletes GSH under acidic conditions. The released silicon and alendronate inhibit osteoclast activation and target bone metastatic lesions.

6. Future Perspectives The detailed catalytic mechanism of the heterogeneous interface can be further explored. Additional bone metastasis tumor models can be adopted to verify the applicability of the material. Metabolomics and transcriptomics can be combined to deeply dissect metabolism-immune crosstalk. Other functional components can be introduced to realize synergistic intervention via multiple pathways.

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