Delivery of coenzyme Q10 with mitochondria-targeted nanocarrier attenuates renal ischemia-reperfusion injury in mice

Abstract

Ischemia-reperfusion (I/R) injury causes high morbidity, mortality, and healthcare costs. I/R induces acute kidney injury through exacerbating the mitochondrial damage and increasing inflammatory and oxidative responses. Here, we developed the mitochondria-targeted nanocarrier to delivery of Coenzyme Q10 (CoQ10) for renal I/R treatment in animal model. The mitochondria-targeted TPP CoQ10 nanoparticles (T-NP_CoQ10) were synthesized through ABC miktoarm polymers method and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The I/R mouse model and oxygen-glucose deprivation/reperfusion (D/R) model were created to examine the role of T-NP_CoQ10 on renal I/R. Mitochondrial DNA damage, apoptosis, and inflammatory cytokines were measured in I/R injury mice. Plasma creatinine, urea nitrogen, tubular injury score was tested to assess the renal function. T-NP_CoQ10 nanoparticles could be delivered to renal mitochondria preciously and efficiently. T-NP_CoQ10 administration attenuated oxidative injury in both cell and animal models significantly, alleviated mtDNA damage, suppressed inflammatory and apoptotic responses, and improved renal function. The mitochondria specific CoQ10 delivery provided a precious and efficient method for protecting inflammatory and oxidative responses of I/R-induced renal damage.