Curcumin-loaded nanoparticles for renal ischemia-reperfusion injuries: Triple-play of redox homeostasis accommodation, lipid metabolism regulation, and nuclear magnetic tracing

Renal ischemia reperfusion (RI/R) injury is a significant pathological process that occurs in acute kidney injury (AKI), and is associated with high mortality rates and poor prognoses. It is therefore essential to explore new therapeutic strategies to enhance treatment outcomes for this condition. Curcumin (Cur), a natural bioactive polyphenolic compound, possesses anti-inflammatory and antioxidant properties. However, its clinical application is limited by poor water solubility and low bioavailability. To overcome these challenges, two amphiphilic molecules were synthesized, PEG-DTPA-DA (PD) and Gd-DTPA-N10 (G). By self-assembling PD and G while loading Cur, a nanoparticle was successfully prepared, PDG@Cur, which served three functions: regulation of lipid metabolism, maintenance of redox homeostasis, and function as a nuclear magnetic resonance (NMR) tracer. <i>In vitro</i> and <i>in vivo</i> experiments indicated that PDG@Cur exhibited excellent stability, effectively quenching reactive oxygen species (ROS), and demonstrating robust capabilities for NMR imaging. Furthermore, PDG@Cur mitigated renal tissue damage due to its potent antioxidant properties and ability to regulate lipid metabolism. Molecular mechanism studies revealed that Cur directly bound to FABP4, and that PDG@Cur targeted the FABP4/PPARγ pathway to exert pharmacological effects against RI/R injuries. In conclusion, this study may provide a novel therapeutic strategy for the treatment of RI/R injuries.