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.