Defect Engineering of Layered Double Hydroxide Nanosheets as Inorganic Photosensitizers for NIR‐II Photodynamic Hypertrophic Cardiomyopathy Therapy

Abstract Hypertrophic obstructive cardiomyopathy (HOCM) is the most common hereditary cardiovascular disease, whereas its current treatment strategies present many postoperative complications and contraindications. Photodynamic therapy (PDT) is expected to be a new strategy for HOCM due to its minimal side effects, exceptional spatiotemporal precision and low invasiveness. However, developing photosensitizer (PSs) that can be activated by long‐wavelength light with high reactive oxygen species (ROS) generation efficiency to achieve ventricular septal ablation remains a great challenge. Herein, the defect‐rich CoZnW‐layered double hydroxide (DR‐CoZnW‐LDH) is first reported as a highly active PS for NIR‐II photodynamic HOCM therapy. Hydrothermal‐synthesized CoZnW‐LDH are etched by acid treatment to obtain DR‐CoZnW‐LDH nanosheets, which exhibit superior ROS generation activity than that of the pristine CoZnW‐LDH under 1270 nm laser irradiation. Studies reveal that the thickness of the interventricular septum in HCM rats closes to normal level after treatment with bovine serum albumin‐modified DR‐CoZnW‐LDH. Echocardiographic assessments indicate that PDT intervention markedly improves left ventricular outflow tract obstruction and cardiac diastolic function in HCM rats. Furthermore, mechanism studies show that PDT‐derived ROS significantly activates Piezo2 ion channel, which promotes Piezo2‐dependent Ca²⁺ accumulation (increased by fourfold), leading to effective ablation of hypertrophic myocardium and reduction of left ventricular outflow tract gradient.