Rationally Designed Galactose Dendrimer for Hepatocyte-Specific Targeting and Intracellular Drug Delivery for the Treatment of Liver Disorders.

Autor: Sharma R; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States., Porterfield JE; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States., An HT; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States.; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States., Jimenez AS; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States., Lee S; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States.; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States., Kannan S; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States.; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States.; Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, Maryland 21205, United States., Sharma A; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States., Kannan RM; Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.; Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, Maryland 21205, United States.
Jazyk: angličtina
Zdroj: Biomacromolecules [Biomacromolecules] 2021 Aug 09; Vol. 22 (8), pp. 3574-3589. Date of Electronic Publication: 2021 Jul 29.
DOI: 10.1021/acs.biomac.1c00649
Abstrakt: Over two million people die of liver disorders every year globally. Hepatocytes are the key cells affected in several acute and chronic liver diseases. The current clinical outcomes of liver-targeted nanoparticles are limited, necessitating the need to develop smart hepatocyte-targeted drug delivery systems. Here, we present the rational design and development of a hepatocyte-targeting glycodendrimer (GAL-24) built from biocompatible building blocks, using expedite and facile chemical methodology. GAL-24 is designed to inherently target asialoglycoprotein receptor 1 (ASGP-R) on hepatocytes and shows significant accumulation in the liver (20% of injected dose), just 1 h after systemic administration. This is highly specific to hepatocytes, with over 80% of hepatocytes showing GAL-24-Cy5 signal at 24 h. GAL-24-Cy5 maintains hepatocyte-targeting capabilities in both a mouse model of severe acetaminophen poisoning-induced hepatic necrosis and a rat model of nonalcoholic steatohepatitis (NASH). This GAL-24 nanoplatform holds great promise for improved drug delivery to hepatocytes to combat many liver disorders.
Databáze: MEDLINE
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