Hyaluronic Acid-Based ROS-Responsive Nanomicelles for Curcumin Delivery in the Treatment of LPS-Induced Acute Kidney Injury

Acute kidney injury (AKI) is a common clinical syndrome characterized by a rapid decline in kidney function, with inflammation being a key driver. In this study, the hydrophobic drug Rhein was conjugated to hyaluronic acid (HA) via esterification of its carboxyl group. The HA was then modified with 4-hydroxymethylphenylboronic acid pinacol ester (PBAP), which is responsive to reactive oxygen species (ROS). Finally, curcumin was loaded onto this construct to develop a ROS-responsive nanodelivery system (RHP@Cur). In vitro, the nanoparticles showed good ROS responsiveness in H 2 O 2 medium and successfully targeted the CD44 receptors on macrophages. Compared to curcumin alone, RHP@Cur significantly inhibited the secretion of NO and TNF-α and blocked NF-κB activation, with more pronounced effects. RHP itself also exhibited some anti-inflammatory effects. In an in vivo AKI model, the anti-inflammatory effects of RHP@Cur were consistent with the in vitro results. H&E staining results showed that RHP@Cur significantly improved kidney pathological damage. Immunohistochemical results revealed that it reduced the deposition of kidney injury molecule-1 (KIM-1) in the kidneys, with better effects than curcumin and RHP. These results suggest that Rhein exerts a synergistic anti-inflammatory effect, and its potential for combined use with curcumin for kidney therapy makes RHP@Cur more effective than RHP in treating AKI. In addition, since RHP@Cur delivers Cur, it enhances the therapeutic effect of Cur. Therefore, RHP@Cur provides a potential effective means for the treatment of acute kidney injury.