Folate-Targeted Co-Delivery of Curcumin and siRela Nanoparticles Synergistically Treat Sepsis-Associated Acute Kidney Injury.

The increasing burden of Acute Kidney Injury (AKI) significantly impacts human health. Approximately 70% of septic patients develop AKI, which markedly increases the risk of in-hospital mortality. However, current treatment for Sepsis-Associated Acute Kidney Injury (SA-AKI) is mainly supportive, and no specific therapy is available. siRNA therapy is an emerging approach that inhibits mRNA of specific targets to exert therapeutic effects. Based on the gene silencing principle of siRNA, we developed a targeted bifunctional coloaded nanoparticle, PDA@Cur-PEI-PEG-FA/siRela (PCPPFS), using folic acid (FA) as a targeting moiety. In this system, curcumin acts as a therapeutic agent and synergizes with siRela to exert anti-inflammatory and antioxidative stress effects, thereby reducing apoptosis and pyroptosis of renal tubular epithelial cells. This nanosystem demonstrated good targeting and therapeutic effects in both in vitro and in vivo experiments, providing a new approach for SA-AKI therapy.