Novel Pharmacological and Nanotechnology-Based Therapeutic Strategies for MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent global health concern driven by metabolic imbalance and excess caloric intake, leading to hepatic steatosis, inflammation, and fibrosis that may progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, or hepatocellular carcinoma. Current management relies primarily on lifestyle interventions and, in advanced stages, pharmacological therapies; however, long-term outcomes remain limited due to variable efficacy and poor sustainability. Recent advances in pharmacotherapy, including GLP-1 receptor agonists, THR-β agonists and SGLT2 inhibitors, have shown clinically meaningful improvements in metabolic parameters and hepatic steatosis, although their impact on fibrosis and long-term disease modification remains uncertain. In parallel, genomic and nanotechnology-based strategies (such as RNA-based therapies and nanoparticle delivery systems) have emerged as promising approaches to enhance drug stability, targeting, and therapeutic precision. Despite these advances, most emerging strategies remain at preclinical or early translational stages, with significant challenges related to safety, scalability, regulatory approval, and long-term efficacy. In this context, this review provides an integrative synthesis of pharmacological, genomic, and nanotechnology-based therapies, highlighting their mechanisms, limitations, and translational potential. Future research should focus on well-designed clinical trials, standardized evaluation frameworks, and the development of personalized therapeutic approaches. The convergence of these strategies may enable more effective and durable interventions for MASLD.