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ACS Nano

ACS Nano

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Fully Bioactive Nanodrugs: Stem Cell-Derived Exosomes Engineered with Biomacromolecules to Treat CCl4- and Extreme Hepatectomy-Induced Acute Liver Failure

Published:3 December 2024 DOI: 10.1021/acsnano.4c07408
Meng Sun, Min Li, Min Hu, Yueyun Fan, Yanhong Liu, Jian Sun, Jinfeng Zhang

Abstract

Acute liver failure (ALF) is a serious global disease characterized by rapid onset and high mortality. Currently, the clinical treatment of ALF faces considerable hurdles due to limited medication options and the scarcity of liver transplants. Despite biomacromolecules such as hepatocyte growth factor (HGF) and glutathione (GSH) having been applied for ALF symptom relief in the clinic, they still face substantial challenges including poor stability, difficulty in acting on intracellular targets, and inadequate therapeutic outcome. In this work, by taking advantage of the innate targeting and regenerative capabilities of mesenchymal stem cells (MSCs), we harnessed MSC-derived exosomes as natural bioactive carriers for the simultaneous delivery of HGF and GSH, forming a fully bioactive nanodrug termed HG@Exo. Impressively, the HG@Exo demonstrated potent therapeutic effects against both carbon tetrachloride (CCl4)- and extreme hepatectomy-induced ALF through multiple mechanisms, including regulation of oxidative stress, reduction of inflammation, and promotion of hepatocyte regeneration, which were facilitated by its inflammation-targeting to damaged liver tissues. Furthermore, an FDA-approved near-infrared fluorescent dye, indocyanine green (ICG), has been incorporated into the exosomes (HGI@Exo) to endow them with real-time in vivo tracking capability, which showed favorable liver accumulation of the HGI@Exo in both CCl4- and surgery-induced ALF animal models, providing crucial insights into their biodistribution and therapeutic efficacy. Overall, the presented fully bioactive nanodrugs with targeting and theranostic abilities hold significant promise for potentiating the therapeutic efficacy of biomacromolecules for the improved treatment of ALF and other inflammatory diseases.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Glutathione 70-18-8 C10H17N3O6S 1139 suppliers $6.00-$3420.00
Trypsin 9002-07-7 C35H47N7O10 456 suppliers $17.70-$24930.00
Indocyanine green 3599-32-4 C43H49N2NaO6S2 380 suppliers $38.00-$943.00
2-Methyl-2-butanol 75-85-4 C5H12O 368 suppliers $9.00-$1310.00

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