Dual-Targeted Nanoparticles Hitchhiking on <i>Lactobacillus rhamnosus</i> Bacterial Ghosts to Alleviate Nonalcoholic Steatohepatitis

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 <i>Lactobacillus rhamnosus</i> bacterial ghosts (LBGs) to effectively intervene in NASH. <i>In vitro</i> experiments demonstrated that AXT@TWG nanoparticles significantly reduced LPS-induced reactive oxygen species production and apoptosis while effectively alleviating lipid accumulation. <i>In vivo</i> 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.