Core-shell heterostructured nanozyme for alveolar echinococcosis treatment via targeted electron transfer and catalytic reactive oxygen species generation.

Alveolar echinococcosis (AE), a severe parasitic disease, poses a significant therapeutic challenge due to the limitations of surgery and albendazole chemotherapy, particularly the difficulty in achieving targeted drug delivery and disrupting the robust structure of the protoscoleces (PSCs). This study introduces a novel therapeutic strategy of "targeted binding-electron transfer (ET)-osmotic disruption" to address these challenges. We designed a core-shell heterostructure nanoplatform (FZ) composed of a magnetite (Fe3O4) nanozyme core and a zinc oxide (ZnO) semiconductor shell. This architecture strategically overcomes the key limitations of nanozymes, namely instability and insufficient catalytic activity. The ZnO shell physically protects the Fe3O4 core from oxidation and dissolution, thereby preserving the active electron-donating valence state (Fe2+) and ensuring long-term ET capability. Furthermore, the heterostructure enhances the peroxidase-like catalytic activity, with the optimized FZ-2 exhibiting a 41.8% increase over pristine Fe3O4. By modulating the surface charge, the nanoplatform achieves specific targeting and adsorption onto the negatively charged PSCs' surface. The subsequent interfacial ET from FZ-2 disrupts the PSCs' membrane potential, leading to lethal osmotic imbalance and a high efficacy (98%) in inducing PSCs death. This work not only provides a potent nanomedicine for AE but also establishes a pioneering ET-based therapeutic paradigm for treating diseases with complex multicellular barriers.