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

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.