Enhanced Renal Protection in Acute Kidney Injury with ROS-Activated Nanoparticles Targeting Oxidative Stress and Inflammation

Acute kidney injury (AKI) is often associated with oxidative stress, which leads to a range of pathological changes, including inflammation and cell apoptosis. These mechanisms highlight the crucial role of eliminating ROS in the pathogenesis of AKI. This study presented a ROS-activated drug delivery system, NPS_PBA@Hib, designed for the targeted delivery of the anti-inflammatory and antioxidant drug hibifolin (Hib) to the kidneys, marking its inaugural application in AKI therapy. The drug loading of Hib was up to be 15% by conversely binding with the phenylboronic acid parts in the nanoparticles. NPS_PBA@Hib increased cellular uptake of drugs in HK-2 cells and reduced oxidative stress-induced damage by scavenging ROS. The nanoparticles notably extended the retention of Hib in AKI kidneys when compared to healthy kidneys, leading to heightened accumulation in the renal tubules. NPS_PBA@Hib demonstrated Hib’s reno-protective effects by reducing oxidative stress and inflammation. In essence, this research serves as the primary confirmation of Hib’s efficacy in inhibiting NLRP3 signaling pathway for the AKI treatment. The findings suggest that NPS_PBA@Hib nanoparticles are effective in treating AKI, highlighting the promising potential of utilizing Hib as a natural antioxidant nanoplatform for AKI, as well as other ROS-related diseases.