Hepatocytes and mitochondria dual-targeted astaxanthin WPI-SCP nanoparticles for the alleviation of alcoholic liver injury

• Published in: International journal of biological macromolecules 2025-01, Vol.285, p.137992, Article 137992
• Main Authors: Lv, Yueqi, Hao, Sijia, Wang, Yuxiao, Xing, Shanghua, Tan, Mingqian
• Format: Article
• Language: English
• Subjects: Alcoholic liver injury; Astaxanthin; Hepatocyte targeting; Mitochondrial targeting; Sea cucumber peptide
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.137992

Alcoholic liver injury is one of the most frequent liver diseases around the world, and nutritional intervention has been considered as an effective way to alleviate alcohol liver injury. To alleviate the liver damage caused by alcohol, a type of astaxanthin (AXT) loaded nanoparticles were designed for dual targeting of hepatocytes and mitochondria. Firstly, galactooligosaccharides (GOS) were conjugated to whey protein isolate (WPI) and sea cucumber peptide (SCP) via the Maillard reaction, achieving a grafting degree of 29 %, then triphenylphosphonium (TPP) was linked by amide reaction. Secondly, AXT was loaded into the complex of SCP-WPI-GOS-TPP (SWGT) to form AXT@SCP-WPI-GOS-TPP(AXT@SWGT) nanoparticles. The Pearson coefficient increased from 0.69 to 0.76 after introducing TPP targeting moiety. In vivo experiments showed that AXT@SWGT significantly alleviated liver injury caused by alcohol. The vacuolation and fat accumulation associated with alcoholic liver injury was alleviated. The alcohol dehydrogenase and aldehyde dehydrogenase activity were improved by 296.88 % and 34.19 %, respectively. AXT@SWGT significantly enhanced the biological activities of glutathione by 76.86 %, catalase by 145.42 %, and superoxide dismutase by 33.48 %, thereby alleviating oxidative stress. The results indicated that the AXT@SWGT might have the potential to intervene alcoholic liver injury via the dual targeting strategy. •Hepatocytes and mitochondria dual-targeted astaxanthin (AXT) nanoparticles were constructed.•Sea cucumber peptide can shorten Maillard reaction time of nanoparticle preparation.•Enhanced anti-oxidative stress was found for the targeted AXT nanoparticles treatment.•The targeted AXT nanoparticles could alleviate the liver damage of alcoholic liver injured mice.