Neutrophil‐Mediated Nanozyme Delivery System for Acute Kidney Injury Therapy

Reactive oxygen species (ROS) scavenging of nanozymes toward acute kidney injury (AKI) is a current promising strategy, however, the glomerular filtration barrier (GFB) limits their application for treating kidney related diseases. Here, a neutrophil‐mediated delivery system able to hijack neutrophil to transport nanozyme‐loaded cRGD‐liposomes to inflamed kidney for AKI treatment by cRGD targeting integrin αvβ1 is reported. The neutrophil‐mediated nanozyme delivery system demonstrated great antioxidant and anti‐apoptosis ability in HK‐2 and NRK‐52E cell lines. Moreover, in ischemia‐reperfusion (I/R) induced AKI mice, a single dose of LM@cRGD‐LPs 12 h post‐ischemia significantly reduces renal function indicators, alleviates renal pathological changes, and inhibits apoptosis of renal tubular cells and the expression of renal tubular injured marker, thus remarkably reducing the damage of AKI. Mechanistically, the treatment of LM@cRGD‐LPs markedly inhibits the process of Nrf2 to the nucleus and reduces the expression of the downstream HO‐1, achieves a 99.51% increase in renal tissue Nrf2 levels, and an 86.31% decrease in HO‐1 levels after LM@cRGD‐LPs treatment. In short, the strategy of neutrophil‐mediated nanozyme delivery system hold great promise as a potential therapy for AKI or other inflammatory diseases. The LM@cRGD‐LPs nanozyme delivery system, upon systemic administration in a murine model of acute kidney injury (AKI), captures neutrophils which then migrate to the site of renal injury under the influence of inflammatory chemoattractants. The subsequent release via the formation of neutrophil extracellular traps (NETs) contributes to the amelioration of AKI by scavenging reactive oxygen species (ROS) and reducing apoptosis.