Renal-targeted exosomes inhibiting miR-182-5p for treatment of renal ischemia–reperfusion injury

Renal ischemia–reperfusion injury (IRI) is a significant condition that leads to acute kidney injury, exacerbating the progression of renal failure clinically and affecting the patient's prognosis. Following the identification of miR-182-5p as a significant molecule in IRI, we conducted a detailed analysis of its potential downstream genes and assessed its involvement in the SIRT1/Nrf2/ferroptosis pathway. To validate these findings in vivo, we implemented an exosome-mediated drug delivery protocol and assessed its therapeutic efficacy in C57BL/6. miR-182-5p exhibited a notable upregulation in renal IRI. Utilizing bioinformatics approaches, the study further investigated and validated its downstream SIRT1/Nrf2 pathway, establishing its role in ferroptosis. By employing LTHVVWL(LTH)-anchored exosomes, the delivery of miR-182-5p to the kidney was significantly improved, thereby illustrating its potential efficacy in mitigating renal IRI. The findings of our study demonstrated that miR-182-5p suppressed SIRT1/Nrf2 activity and facilitated ferroptosis, suggesting its potential as a therapeutic target for clinical IRI treatment. The inhibition of miR-182-5p via LTH-anchored exosomes was shown to significantly mitigate renal IRI, providing a novel approach for the development of miRNA-based therapeutic drug delivery systems.