Liposome‐Mediated Biomimetic Delivery of PLK3 Inhibitor with NIR II‐Triggered Release Prevents Renal Ischemia‐Reperfusion Injury

Abstract As one of the leading causes of acute kidney injury (AKI), ischemia‐reperfusion injury (IRI) results in tubular necrosis and renal inflammation. Here, from gene screening, it is found that Polo‐like kinase 3 (PLK3), but not other PLKs, is highly up‐regulated during mouse IRI. In vivo administration of PLK3 inhibitor alleviates IRI‐induced AKI, but induces myelosuppression. Thus, a novel liposome‐mediated biomimetic delivery system with 1080 nm near infrared (NIR)‐triggered release to specifically and efficiently delivering the inhibitor to the kidney is developed. NIR light irradiation to kidney results in an excellent effect for reduced immune cell infiltration and renal inflammation. Mechanistically, PLK3 inhibition suppresses the degradation of hypoxia‐inducible factor‐1α (HIF‐1α) and reactive oxygen species (ROS)‐mediated oxidative stress, thus protecting the renal tubular epithelial cells from cell death and preventing macrophage activation and renal inflammation. Thus, the NIR light‐triggered liposome system provides an efficient candidate treatment for AKI without systemic side effect.