Mitochondria-targeted coenzyme Q10 nanocarriers evaluated by particle size and lipid composition alleviate early acetaminophen-induced liver injury.

Acetaminophen (APAP) overdose-induced liver damage is a serious clinical issue primarily caused by mitochondrial dysfunction in hepatocytes. Coenzyme Q10 (CoQ10) exhibits mitochondrial protective effects and is considered a promising therapeutic candidate. However, it has difficulty targeting liver mitochondria because of its high hydrophobicity and low bioavailability. To address the therapeutic limitations of CoQ10 caused by poor mitochondrial bioavailability, this study aimed to establish a rational design to systematically evaluate how particle size and lipid composition influence the therapeutic efficacy of CoQ10-loaded nanocarriers on APAP-induced liver injury (AILI). Three types of CoQ10-loaded mitochondrial-targeted nanocarriers (CoQ10-MITO-Porter) of different particle sizes (50, 100, 200 nm) and CoQ10-LP, which mimics liposomes used in clinical applications, were prepared using a microfluidic device. These nanocarriers were administered to AILI model mice at early stages of disease, and their hepatic and mitochondrial accumulation, therapeutic impact on serum biomarkers, histological damage, and CoQ10 delivery efficiency were evaluated systematically. The 50-nm CoQ10-MITO-Porter showed the highest hepatoprotective efficacy, indicated by marked attenuation of serum alanine aminotransferase levels and reduced hepatic necrosis. The effect decreased with increasing particle size and was minimal for CoQ10-LP. These results highlight the importance of systematic evaluation of nanocarrier physicochemical properties to achieve effective mitochondrial delivery of CoQ10 in early-phase AILI. These findings are expected to serve as a foundation for the development of mitochondria-targeted nanomedicines that alleviate early-phase hepatic damage and may extend to other mitochondrial-related diseases.