From Bench to Bedside: Multifunctional Nanoplatforms in the Fight Against Non-alcoholic Fatty Liver Disease

Yu Zhao,1,* Luting Wang,2,3,* Shengrui Zhu,4 Rui Feng,5 Wei Zhang1 1Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 3School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of General Practice, Tiantai People’s Hospital of Zhejiang Province, Tiantai, Zhejiang, People’s Republic of China; 5Department of Interventional Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang, Email zhangwei1@hmc.edu.cnAbstract: Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population and represents a major public health burden, characterized by disease progression from steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma. Despite this high prevalence and serious clinical outcomes, no pharmacologic therapies are currently approved, and standard lifestyle interventions often prove ineffective. Therefore, there is a major unmet clinical need for innovative treatments. To overcome these limitations, nanomedicine has emerged as a promising approach, with multifunctional nanoplatforms (MFNs) demonstrating distinctive advantages in tackling the complex pathology of NAFLD. For instance, MFNs enable targeted liver delivery, synergistic therapeutic effects (eg, reducing hepatic lipogenesis and fibrosis), and theranostic integration, thereby minimizing rapid clearance and adverse effects associated with conventional low-molecular-weight compounds. Consequently, this review comprehensively synthesizes the latest advances in MFNs for NAFLD management, critically analyzing their design strategies (eg, nanoencapsulation of bioactive compounds for enhanced bioavailability) and mechanistic roles in ameliorating inflammation, fibrosis, and steatosis. Furthermore, it explores challenges such as optimizing organ-specific targeting and personalized applications, while outlining future research directions to accelerate clinical translation and address coexisting conditions like chronic hepatitis B infection. By bridging current knowledge gaps, this work aims to inform the development of effective nanotherapeutic strategies for NAFLD.Keywords: non-alcoholic fatty liver disease, multifunctional nanoplatforms, synergistic therapy, theranostic nanoplatforms, clinical translation