TY - JOUR
T1 - Rationally Designed Galactose Dendrimer for Hepatocyte-Specific Targeting and Intracellular Drug Delivery for the Treatment of Liver Disorders
AU - Sharma, Rishi
AU - Porterfield, Joshua E.
AU - An, Hyoung Tae
AU - Jimenez, Ambar Scarlet
AU - Lee, Seulki
AU - Kannan, Sujatha
AU - Sharma, Anjali
AU - Kannan, Rangaramanujam M.
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/8/9
Y1 - 2021/8/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85112535746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85112535746&partnerID=8YFLogxK
U2 - 10.1021/acs.biomac.1c00649
DO - 10.1021/acs.biomac.1c00649
M3 - Article
C2 - 34324818
AN - SCOPUS:85112535746
SN - 1525-7797
VL - 22
SP - 3574
EP - 3589
JO - Biomacromolecules
JF - Biomacromolecules
IS - 8
ER -