Levan-stabilized Prussian blue nanoparticles targeting the CD44 receptor for the effective treatment of acute kidney injury.

Acute kidney injury (AKI) is a prevalent disease characterized by sudden loss of renal function. Nanozymes have emerged as promising therapeutic candidates because of their intrinsic reactive oxygen species (ROS)-scavenging capabilities and anti-inflammatory efficacy. However, their clinical translation has been hindered by limited bioavailability and lack of targeted tissue specificity. In this study, ROS-scavenging Prussian blue nanozymes were stabilized with levan polysaccharide (L-PB) to improve their colloidal stability, biocompatibility, and inflammation site-targeting ability. The resulting L-PB exhibited a stable hydrodynamic diameter of ∼100 nm under physiological conditions for up to 2 weeks. In vitro assays confirmed the biocompatibility, effective ROS-scavenging activity, and significantly higher cellular internalization of L-PB than that of Prussian blue stabilized with bovine serum albumin (B-PB). In a glycerol-induced murine model of AKI, L-PB demonstrated selective accumulation in CD44 receptor-overexpressing injured kidneys and exhibited excellent therapeutic effects by mitigating oxidative stress and inflammation, with minimal systemic toxicity compared with B-PB. These findings indicate that L-PB, with CD44 active targeting, has potential as a novel targeted AKI therapeutic, enabling efficient treatment of various inflammation-related diseases.