Engineering the electronic structure of Fe-MoO2@PEG to increase sonodynamic and multi-nanozyme activities for anticancer therapy.

Both sonodynamic therapy (SDT) and nanozymes can be considered specialized forms of catalysis, which are related to the electron structure. In this work, Fe doping was employed to introduce electronic localization and spin polarization toward porous MoO₂ nanospheres to improve the anticancer catalytic efficiency. All the Fe atoms are single-distributed to substitute for some lattice positions of Mo. Compared with MoO₂@PEG, MoO₂/Fe@PEG results in a 2.8-fold increase in ROS generation, which is attributed to spin polarization. This phenomenon enhances charge separation, increases conductivity, and promotes O₂ adsorption, thereby significantly improving the ROS production efficiency. Furthermore, MoO₂/Fe@PEG also has superior mimic-catalase (CAT) activity (318,467 U g^-1), which is even greater than that of natural catalase (220,834 U g^-1). Compare with MoO₂@PEG Fe doping increased the activity by 76.0 times because electron localization can decrease the free energy of the redox reaction. This novel CAT ability can convert endogenous H₂O₂ into O₂, alleviating tumor hypoxia and increasing ROS production. Notably, MoO₂/Fe@PEG also mimics GSH oxidase and NADPH oxidase (NOX) activities to consume GSH and restrain its regeneration at the same time, contributing to oxidative stress. The synergistic effects of SDT and multiple enzymes not only exhibit potent tumor inhibition but also elicit a robust immune response to prevent metastasis and recurrence.