PT  - JOURNAL ARTICLE
AU  - Tang, Tao-Tao
AU  - Wang, Bin
AU  - Wu, Min
AU  - Li, Zuo-Lin
AU  - Feng, Ye
AU  - Cao, Jing-Yuan
AU  - Yin, Di
AU  - Liu, Hong
AU  - Tang, Ri-Ning
AU  - Crowley, Steven D.
AU  - Lv, Lin-Li
AU  - Liu, Bi-Cheng
TI  - Extracellular vesicle–encapsulated IL-10 as novel nanotherapeutics against ischemic AKI
AID  - 10.1126/sciadv.aaz0748
DP  - 2020 Aug 01
TA  - Science Advances
PG  - eaaz0748
VI  - 6
IP  - 33
4099  - http://advances.sciencemag.org/content/6/33/eaaz0748.short
4100  - http://advances.sciencemag.org/content/6/33/eaaz0748.full
SO  - Sci Adv2020 Aug 01; 6
AB  - Recently, extracellular vesicles (EVs) have been attracting strong research interest for use as natural drug delivery systems. We report an approach to manufacturing interleukin-10 (IL-10)–loaded EVs (IL-10+ EVs) by engineering macrophages for treating ischemic acute kidney injury (AKI). Delivery of IL-10 via EVs enhanced not only the stability of IL-10, but also its targeting to the kidney due to the adhesive components on the EV surface. Treatment with IL-10+ EVs significantly ameliorated renal tubular injury and inflammation caused by ischemia/reperfusion injury, and potently prevented the transition to chronic kidney disease. Mechanistically, IL-10+ EVs targeted tubular epithelial cells, and suppressed mammalian target of rapamycin signaling, thereby promoting mitophagy to maintain mitochondrial fitness. Moreover, IL-10+ EVs efficiently drove M2 macrophage polarization by targeting macrophages in the tubulointerstitium. Our study demonstrates that EVs can serve as a promising delivery platform to manipulate IL-10 for the effective treatment of ischemic AKI.