Che Tongtong, Song Yukun, Su Wentao, Xing Shanghua, Wang Haitao, Tan Mingqian
Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Qinggongyuan1, Ganjingzi District, Dalian 116034, Liaoning, China.
National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, Liaoning, China.
Food Funct. 2023 Mar 20;14(6):2908-2920. doi: 10.1039/d2fo04036k.
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.
非酒精性脂肪性肝病（NAFLD）是一种代谢综合征疾病。在此，构建了肝实质细胞和线粒体靶向纳米载体，将虾青素（AST）递送至肝组织，以最大限度地提高AST的干预效率。通过美拉德反应将半乳糖（Gal）偶联到乳清分离蛋白（WPI）上，利用其识别肝细胞中特异性表达的去唾液酸糖蛋白受体，实现对肝实质细胞的靶向。通过酰胺化反应将三苯基膦（TPP）接枝到糖基化的WPI上，使纳米载体（AST@TPP-WPI-Gal）具备双重靶向能力。AST@TPP-WPI-Gal纳米载体可靶向脂肪变性的HepG2细胞中的线粒体，具有增强的抗氧化和抗脂肪生成作用。通过NAFLD小鼠模型验证了AST@TPP-WPI-Gal靶向肝组织的能力，结果表明，与游离AST相比，AST@TPP-WPI-Gal可调节血脂紊乱、保护肝功能，并显著降低肝脏脂质积累（40%）。因此，AST@TPP-WPI-Gal可能具有作为NAFLD营养干预双重靶向肝制剂的潜力。
