Hepatic parenchymal cell and mitochondrial-targeted astaxanthin nanocarriers for relief of high fat diet-induced nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic syndrome disorder. Here, hepatic parenchymal cell and mitochondrial-targeted nanocarriers were constructed to deliver astaxanthin (AST) to liver tissue to maximize AST intervention efficiency. The hepatic parenchymal cell-targeting was achieved using galactose (Gal) conjugated onto whey protein isolate (WPI) through the Maillard reaction by recognizing asialoglycoprotein receptors specifically expressed in hepatocytes. Grafting triphenylphosphonium (TPP) onto glycosylated WPI by an amidation reaction enabled the nanocarriers (AST@TPP-WPI-Gal) to achieve dual targeting capability. The AST@TPP-WPI-Gal nanocarriers could target mitochondria in steatotic HepG2 cells with an enhanced anti-oxidative and anti-adipogenesis effect. The ability of AST@TPP-WPI-Gal to target liver tissue was verified by an NAFLD mice model, and the results showed that AST@TPP-WPI-Gal could regulate blood lipid disorders, protect liver function, and remarkably reduce liver lipid accumulation (40%) compared with that of free AST. Therefore, AST@TPP-WPI-Gal might have potential as a dual targeting hepatic agent for nutritional intervention for NAFLD.