Open Access

Evaluation of the liver targeting and anti‑liver cancer activity of artesunate‑loaded and glycyrrhetinic acid‑coated nanoparticles

  • 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
  • View Affiliations

  • Published online on: September 21, 2023     https://doi.org/10.3892/etm.2023.12215
  • Article Number: 516
  • Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 in vivo. 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.
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November-2023
Volume 26 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Pan X, Huang J, Liu S, Shao Y, Xi J, He R, Shi T, Zhuang R and Bao J: Evaluation of the liver targeting and anti‑liver cancer activity of artesunate‑loaded and glycyrrhetinic acid‑coated nanoparticles. Exp Ther Med 26: 516, 2023.
APA
Pan, X., Huang, J., Liu, S., Shao, Y., Xi, J., He, R. ... Bao, J. (2023). Evaluation of the liver targeting and anti‑liver cancer activity of artesunate‑loaded and glycyrrhetinic acid‑coated nanoparticles. Experimental and Therapeutic Medicine, 26, 516. https://doi.org/10.3892/etm.2023.12215
MLA
Pan, X., Huang, J., Liu, S., Shao, Y., Xi, J., He, R., Shi, T., Zhuang, R., Bao, J."Evaluation of the liver targeting and anti‑liver cancer activity of artesunate‑loaded and glycyrrhetinic acid‑coated nanoparticles". Experimental and Therapeutic Medicine 26.5 (2023): 516.
Chicago
Pan, X., Huang, J., Liu, S., Shao, Y., Xi, J., He, R., Shi, T., Zhuang, R., Bao, J."Evaluation of the liver targeting and anti‑liver cancer activity of artesunate‑loaded and glycyrrhetinic acid‑coated nanoparticles". Experimental and Therapeutic Medicine 26, no. 5 (2023): 516. https://doi.org/10.3892/etm.2023.12215