Platelet shipped IL-10 enhances drug delivery for attenuating I/R- or UUO-induced renal injury.

• Platelet camouflaged IL-10 is a promising approach for kidney injury treatment. • IL-10@PLT could selectively accumulate in injured kidneys. • IL-10@PLT could be activated, aggregated, and released IL-10 in the injury kidney. • High accumulation and strong anti-inflammatory of IL-10@PLT enhanced therapeutic efficiency. Inflammatory factors have emerged as key pathophysiological molecules involved in the progression of acute and chronic kidney disease. However, the anti-inflammatory effect of interleukin-10 (IL-10) is largely attenuated because of its insufficient concentration in an injured kidney. To overcome this challenge, we demonstrate in this study that platelet (PLT) camouflaged IL-10 (IL-10@PLT) can selectively accumulate in injured kidneys for treating kidney inflammation and resulting complications. In this system, the PLT drug carrier maintained its original attributes over the study duration, with a good inflammation target effect, confirmed by in vivo imaging. IL-10@PLT could be activated and aggregated, and also released IL-10 at the injury site in the kidney because of high levels of Tumor Necrosis Factor-α (TNF-α). Compared with free IL-10, IL-10@PLT displayed a higher anti-inflammatory effect with fewer mitochondrial disorders (P < 0.01) and lower expression of NOD-like receptor (NLR)-P3 (NLRP3) (P < 0.05), resulting in reduced inflammation and pyroptosis in ischemia/reperfusion injury (I/R) mice. Treatment with IL-10@PLT also exhibited significantly reduced nuclear factor kappa-B (NF-kB) expression, reduced inflammatory response, as well as improved renal fibrosis (P < 0.05) in the recovery phase in unilateral ureteral obstruction (UUO) mice. At the same time, IL-10@PLT therapy continued to exhibit a favorable safety profile. This study established a promising approach for I/R- and UUO-induced kidney injury and fibrosis by taking advantage of the high accumulation and strong anti-inflammatory of IL-10@PLT. Our study also reveals the importance PLT as an effective drug carrier for targeted therapies. [ABSTRACT FROM AUTHOR]