Coupling Pt Single-Atoms with Amorphous LDH Nanosheets as a High-Efficiency Sonosensitizer for Sonodynamic Immunotherapy – Research

Sonodynamic therapy (SDT) represents a minimally invasive alternative for cancer treatment. However, its efficacy is constrained by the insufficient reactive oxygen species generation of inorganic sonosensitizers due to wide bandgaps, rapid electron-hole recombination, and insufficient oxygen adsorption/activation. Herein, we report for the first time a novel sonosensitizer constructed by anchoring Pt single-atoms onto amorphous CoMgMo-layered double hydroxide (Pt/a-LDH) for high-efficiency sonodynamic immunotherapy. Through the synergy of defect engineering and single-atom modification, Pt/a-LDH achieves sharp bandgap reduction (from 2.4 to 0.6 eV) and abundant defective environment, dramatically promoting charge separation and inhibiting electron-hole recombination (an inhibition rate of 89.8%). Moreover, the unique 2D structure and hydroxyl coordination environment of LDH yield ultrahigh single-atom loading efficiency and defect density, which significantly promote oxygen adsorption/activation, reduce reaction energy barrier (bond energy from 3.6 to 2.1 eV), and accelerate reaction kinetics. Consequently, Pt/a-LDH achieves a significant enhancement in sonodynamic performance, generating singlet oxygen at 5.3 and 38.2 times that of CoMgMo-LDH and TiO₂ sonosensitizer, respectively. In vivo assays demonstrate that polyethylene glycol-modified Pt/a-LDH induces robust immunogenic cell death, activates dendritic cell maturation, stimulates T-cell infiltration, and reprograms the immunosuppressive tumor microenvironment, offering a new paradigm for high-performance sonodynamic immunotherapy.