High-Entropy Oxide-Phosphomolybdic Acid Ultrathin Nanoleaves with Lattice Strain and Periodic Heterostructures for Enhanced Synthetic Catalytic/Sonodynamic/Immune Therapy

The landscape of nanocatalytic therapy and sonodynamic therapy (SDT) is confronted with formidable challenges, including the rapid consumption of nonrenewable Fenton-like nanocatalysts, inefficient carrier separation in sonosensitizers, and hypoxia in tumor microenvironment (TME). Herein, we develop high-entropy oxide (HEO)-phosphomolybdic acid (PMA) ultrathin nanoleaves in subnanoscale (SHPL), featuring periodic heterounit alternation of HEO nuclei and PMA clusters with obvious lattice tensile strain. Notably, the lattice tensile strain in this leaf structure reduces hydrogen peroxide (H 2 O 2 ) dissociation/adsorption energies, promoting chemodynamic therapy (CDT)-mediated hydroxyl radical ( • OH) generation and oxygen (O 2 ) production to alleviate hypoxia for enhanced SDT. More importantly, the periodic HEO-PMA heterostructures serve as charge mediators, enabling efficient separation of ultrasound (US)-induced electron–holes to augment singlet oxygen ( 1 O 2 ) yield for SDT. Additionally, the well-engineered energy band structure enables excited electrons to flow smoothly to HEO units, rapidly converting Fe III to Fe II as regenerated Fenton-like nanocatalysts and boosting CDT in the TME. As a result, the SHPL exhibits more than 30-fold reactive oxygen species (ROS) production in simulated TME. The enhanced nanocatalytic reactions and SDT fully activate immune response, achieving the suppression of tumor metastases.