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

Abstract

ABSTRACT 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 TiO 2 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.