Evaluation of the Liver Targeting and Anti‑liver Cancer Activity of Artesunate‑loaded and Glycyrrhetinic Acid‑coated Nanoparticles

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2023 Oct 19

PMID 37854499

Authors

Xu-Wang Pan

Jin-Song Huang

Shou-Rong Liu

Yi-Dan Shao

Jian-Jun Xi

Ruo-Yu He

Ting-Ting Shi

Rang-Xiao Zhuang

Jian-Feng Bao

Affiliations

Soon will be listed here.

Abstract

Globally, liver cancer ranks among the most lethal cancers, with chemotherapy being one of its primary treatments. However, poor selectivity, systemic toxicity, a narrow treatment window, low response rate and multidrug resistance limit its clinical application. Liver-targeted nanoparticles (NPs) exhibit excellent targeted delivery ability and promising effectivity in treating liver cancer. The present study aimed to investigate the liver-targeting and anti-liver cancer effect of artesunate (ART)-loaded and glycyrrhetinic acid (GA)-decorated polyethylene glycol (PEG)-poly (lactic-co-glycolic acid) (PLGA) (ART/GA-PEG-PLGA) NPs. GA-coated NPs significantly increased hepatoma-targeted cellular uptake, with micropinocytosis and caveolae-mediated endocytosis as its chief internalization pathways. Moreover, ART/GA-PEG-PLGA NPs exhibited pro-apoptotic effects on HepG2 cells, mainly via the induction of a high level of reactive oxygen species, decline in mitochondrial membrane potential and induction of cell cycle arrest. Additionally, ART/GA-PEG-PLGA NPs induced internal apoptosis pathways by upregulating the activity of cleaved caspase-3/7 and expression of cleaved poly (ADP-Ribose)-polymerase and Phos-p38 mitogen-activated protein kinase in HepG2 cells. Furthermore, ART/GA-PEG-PLGA NPs exhibited higher liver accumulation and longer mean retention time, resulting in increased bioavailability. Finally, ART/GA-PEG-PLGA NPs promoted the liver-targeting distribution of ART, increased the retention time and promoted its antitumour effects . Therefore, ART/GA-PEG-PLGA NPs afforded excellent hepatoma-targeted delivery and anti-liver cancer efficacy, and thus, they may be a promising strategy for treating liver cancer.

Citing Articles

Recent advances in polymeric nanoparticles for the treatment of hepatic diseases.

Gao F, Feng X, Li X Front Pharmacol. 2025; 16:1528752.

PMID: 39925843 PMC: 11802823. DOI: 10.3389/fphar.2025.1528752.

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