| Summary: | Background: Nonalcoholic steatohepatitis (NASH), a severe systemic and inflammatory subtype of nonsalcoholic fatty liver disease, eventually develops into cirrhosis and hepatocellular carcinoma with few options for effective treatment. Currently potent small molecules identified in preclinical studies are confronted with adverse effects and long-term ineffectiveness in clinical trials. Nevertheless, highly specific delivery tools designed from interdisciplinary concepts may address the significant challenges by either effectively increasing the concentrations of drugs in target cell types, or selectively manipulating the gene expression in liver to resolve NASH. Scope of review: We focus on dissecting the detailed principles of the latest interdisciplinary advances and concepts that direct the design of future delivery tools to enhance the efficacy. Recent advances have indicated that cell and organelle-specific vehicles, non-coding RNA research (e.g. saRNA, hybrid miRNA) improve the specificity, while small extracellular vesicles and coacervates increase the cellular uptake of therapeutics. Moreover, strategies based on interdisciplinary advances drastically elevate drug loading capacity and delivery efficiency and ameliorate NASH and other liver diseases. Major conclusions: The latest concepts and advances in chemistry, biochemistry and machine learning technology provide the framework and strategies for the design of more effective tools to treat NASH, other pivotal liver diseases and metabolic disorders.
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