Available online 2 May 2023, 101730

Novel membrane antigens specifically mediate the delivery of therapeutics into major subsets of liver cells to suppress pathogenesis of NASH.

Targeting mitochondria-located circRNAs specifically resolves the inflammation in NASH.

Spherical nucleic acids, non-coding RNA, coacervate and small extracellular vesicles significantly enhance the efficiency of hepatic delivery and gene manipulation to treat NASH.

Machine-learning technology greatly accelerates the design of optimal drug-excipient pair to increase drug loading capacity in treating liver diseases.

Nonalcoholic steatohepatitis (NASH), a severe systemic and inflammatory subtype of nonalcoholic 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.

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.

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.

NASH therapeutics

nanoparticle

specific delivery

integration

© 2023 Published by Elsevier GmbH.