Zhang Xiumin, Liu Ronggang, Chen Yannan, Wang Huihui, Su Wentao, Song Yukun, Tan Mingqian
State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian, Liaoning 116034, China.
Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, China.
ACS Nano. 2025 Apr 15;19(14):14010-14027. doi: 10.1021/acsnano.4c18280. Epub 2025 Apr 3.
Oral nutritional interventions for nonalcoholic steatohepatitis (NASH) have garnered significant interest due to their potential benefits. Astaxanthin (AXT) has the potential to enhance liver function and act as an effective antioxidant for NASH intervention, but its application is limited by its stability and bioavailability. This study aims to develop dual-targeted AXT nanoparticles (AXT@TWG) for precise liver-targeted delivery by ″hitchhiking″ on bacterial ghosts (LBGs) to effectively intervene in NASH. experiments demonstrated that AXT@TWG nanoparticles significantly reduced LPS-induced reactive oxygen species production and apoptosis while effectively alleviating lipid accumulation. experiments demonstrated that LBGs significantly enhanced the intestinal accumulation efficiency of AXT@TWG. Pharmacokinetic evaluations revealed that the efficiency of AXT@TWG@LBGs entering the bloodstream was approximately 2.7 times higher than that of AXT@TWG nanoparticles and their accumulation in the liver was about 1.3 times greater. AXT@TWG@LBGs effectively alleviated NASH by reducing triglycerides, free fatty acids, and malondialdehyde levels by 23.07, 65.32, and 21.42%, respectively, compared to the model group, thereby mitigating lipid accumulation and enhancing antioxidant capacity. Additionally, AXT@TWG@LBGs effectively reduced insulin resistance, lowered inflammatory cytokine levels, and corrected disturbances in lipid metabolism. Therefore, this study provides a potentially effective strategy for the treatment of NASH.
非酒精性脂肪性肝炎（NASH）的口服营养干预因其潜在益处而备受关注。虾青素（AXT）有增强肝功能的潜力，可作为NASH干预的有效抗氧化剂，但其应用受稳定性和生物利用度限制。本研究旨在通过搭乘细菌幽灵（LBGs）开发双靶向AXT纳米颗粒（AXT@TWG），实现肝脏精准靶向递送，以有效干预NASH。实验表明，AXT@TWG纳米颗粒显著降低脂多糖诱导的活性氧生成和细胞凋亡，同时有效减轻脂质积累。实验表明，LBGs显著提高了AXT@TWG的肠道蓄积效率。药代动力学评估显示，AXT@TWG@LBGs进入血液的效率比AXT@TWG纳米颗粒高约2.7倍，其在肝脏中的蓄积量约大1.3倍。与模型组相比，AXT@TWG@LBGs通过分别降低甘油三酯、游离脂肪酸和丙二醛水平23.07%、65.32%和21.42%，有效减轻了NASH，从而减轻脂质积累并增强抗氧化能力。此外，AXT@TWG@LBGs有效降低胰岛素抵抗，降低炎症细胞因子水平，并纠正脂质代谢紊乱。因此，本研究为NASH的治疗提供了一种潜在有效的策略。
