Iridium cluster/hafnium-porphyrin framework heterojunctions for biocatalytic ROS-scavenging and acute kidney injury alleviation.

The clinical treatments of acute kidney injury (AKI) face significant challenges from complex microenvironments caused by excessive reactive oxygen species (ROS) and severe inflammation. Up to now, effective treatments remain scarce. In this study, we propose a versatile and effective biocatalytic heterojunction, Ir@Hf-TCPP, developed by growing iridium clusters on hafnium-tetrakis (4-carboxyphenyl) porphyrin (Hf-TCPP) through a readily accessible solvothermal approach. The metal‑oxygen bonds between the Ir clusters and Hf-TCPP ensure structural stability and adequate exposure of the surface active sites. Moreover, such interfacial features can efficiently accommodate the electronic structure of Ir@Hf-TCPP through the electronic interaction of the formed Hf-O-Ir bridge and boost the biocatalytic antioxidase-like performance. As a result, the optimized Ir@Hf-TCPP antioxidant demonstrates robust and broad-spectrum ROS scavenging performance, providing cytoprotective effects by enhancing endogenous antioxidant defense and maintaining mitochondrial homeostasis in renal tubular epithelia. In a murine rhabdomyolysis-induced AKI model, Ir@Hf-TCPP significantly ameliorated kidney injury by suppressing the MEKK1/JNK/p38 signaling pathway. Additionally, the Ir@Hf-TCPP exhibited effective renal accumulation and excellent biocompatibility in vivo. The beneficial impact and favorable biocompatibility of Ir@Hf-TCPP will promote the management of AKI and other ROS-associated diseases.