Emerging Approaches for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease: The Application of Nanomedicines

Te Shi,1, Haiyan Yue,1, Wen Wang,2, Yu Gao,1 Sheng Xu,1 Jie Gao,3 Chuan Yin4 1Department of Gastroenterology, Naval Medical Center, Naval Medical University, Shanghai, 200050, People’s Republic of China; 2Department of Marine Biomedicine and Polar Medicine, Naval Medical Center, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 4Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Chuan Yin, Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China, Email ilse1225@163.com Jie Gao, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China, Email gaojiehighclea@smmu.edu.cnAbstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 25% of the global population, with limited pharmacological treatment options. While lifestyle modification remains foundational, nanomedicine offers promising strategies to overcome drug delivery challenges, including poor solubility, low bioavailability, and off-target effects. This review systematically examines nanomedicine design strategies across four therapeutic domains: (1) lipid metabolism regulation, (2) anti-inflammatory and antioxidant therapy, (3) insulin sensitization, and (4) gene regulation. We critically analyze hepatic cell-specific targeting approaches, evaluate the biological effects of nanomedicines beyond drug delivery, and discuss the strengths and limitations of current preclinical evidence. Key challenges for clinical translation are examined, including long-term biosafety, animal model relevance, and the gap between preclinical promise and clinical reality. While recent FDA approvals of semaglutide and resmetirom for MASH with fibrosis represent significant progress, nanomedicine may address unmet needs through combination therapies, cell-specific targeting, and theranostic approaches. By integrating emerging trends in intelligent nanomedicine design, this review provides a roadmap for advancing nanomedicines from bench to bedside for MASLD treatment. The infographic illustrates the progression of liver conditions from MASH to cirrhosis and HCC, highlighting the role of nanomedicines in delaying MASLD. The top section shows the progression from MASH to cirrhosis and HCC. The central part emphasizes delaying MASLD progression with nanomedicines. The left section lists nanomedicine types: liposome, nanoemulsions, metal nanoparticle, micelle, carbon nanotube, vesicle and polymeric nanoparticle. The right section shows mechanisms: entrapment, adsorption and bonding. The bottom section presents drug types: hypolipidemic drugs, anti-inflammatory and antioxidant drugs, drugs to improve insulin resistance and gene therapy drugs.Infographic on MASLD progression, nanomedicines and drug types to delay disease.Keywords: metabolic dysfunction-associated steatotic liver disease, nanomedicines, drug delivery, targeted therapy