Nano-Self-Assembled Particles Loaded with Aldehyde Dehydrogenase 2 Agonist Inhibit Ischemia-Reperfusion Injury of Transplanted Kidneys

- and oxygen-glucose deprivation- and -reoxygenation-induced oxidative stress and apoptosis in HK-2 and HUVECs. In vivo, using a rat DCD kidney transplantation model, A-NCH-administered HMP accelerated kidney graft function recovery and alleviated renal tubular injury. Mechanistically, A-NCH activated ALDH2, inhibited the P38 MAPK pathway, promoted nuclear translocation of TEAD4/YAP1, and suppressed the transition of proximal tubule cells to an injured phenotype. In this study, the solubility and drug loading of Alda-1 were improved by 5β-cholanic acid modification of O-HTCC, which proved the synergistic efficacy with HMP in DCD kidney repair and provided a translatable strategy to expand the donor pool.