Manganese‐Doped Piezoelectric Layered Double Hydroxides Induce Catalytic Therapy and Ferroptosis

ABSTRACT 2D Piezoelectric materials have been employed as a novel alternative sonosensitizer for sonopiezoelectric therapy. However, the unsatisfactory piezoelectric response and limited ROS generation efficiency are serious bottlenecks for the practical application. Herein, an ultrathin, defect‐rich piezoelectric sonosensitizer is fabricated through doping Mn in a layered double hydroxide to enhance its piezoelectric response and sonopiezoelectric therapy effect. Theory calculation and experimental results reveal that Mn doping not only induces lattice distortion and surface charge redistribution, leading to an enhanced piezoelectric response, but also modulates the electronic structure to generate abundant defective active sites, which promote the generation of free charges by inhibition of electron–hole recombination. Upon US irradiation, the sonosensitizer exhibits significantly amplified reactive oxygen species (ROS) generation capacity. Moreover, due to its Mn‐doping‐induced catalase‐like enzymatic activity, this sensitizer catalyzes the endogenous H 2 O 2 into O 2 in the tumor microenvironment, thereby further promoting the generation of 1 O 2 under US irradiation. Moreover, the sonosensitizer exhibits enhanced peroxidase‐like activity, likely because Mn doping induces a negative shift in the d ‐band center and lowers the energy barriers of reaction intermediates. Therefore, the material causes both apoptosis and ferroptosis due to the accumulated ROS and a decreased GPX4 level, resulting in an enhanced therapeutic outcome.