Defect-engineered nanoscale metal-organic frameworks as self-cascade antioxidation nanozymes for targeted therapy of cisplatin-induced acute kidney injury

Metal-organic frameworks (MOFs)-based antioxidant nanozymes are promising candidates for the treatment of acute kidney injury (AKI) with high morbidity and mortality. Nevertheless, the excessive size and limited catalytic activity of MOFs still largely restrict their application in the AKI therapy. Herein, we report a defect engineering-based strategy to achieve the controllable design of nanoscale defect-rich MOFs (nMOFs) with strong catalase (CAT)-superoxide dismutase (SOD) self-cascade enzyme-like activities. These nMOFs possess an average size of 24.5 ± 3.5 nm, which facilitates their passive targeting to the kidney. Meanwhile, both SOD and CAT-like activity of nMOFs is enhanced by about 2-fold compared with that of the pristine MOFs due to the presence of rich defects. Furthermore, L-serine with kidney injury molecule 1 (Kim-1) targeting property is modified on the surface of nMOFs (LS-nMOFs) to endow the materials with enhanced targeting property for effective treatment of cisplatin-induced AKI (CP-AKI). Both in vitro and in vivo results demonstrated that LS-nMOFs can inhibit oxidative stress and apoptosis in the kidney by self-cascade antioxidant scavenging of reactive oxygen species, which ultimately realize the effective treatment of CP-AKI in a mouse model. This work paves a new avenue for engineering MOF-based antioxidant systems for the treatment of oxidative stress-mediated diseases.