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A pH‑responsive hyaluronic acid nano‑vehicle co‑encapsulating doxorubicin and all‑trans retinoic acid for the inhibition of hepatic stellate cell‑induced tumor growth and metastasis

  • Authors:
    • Qiao Lu
    • Xueyang Gong
    • Guangtao Jia
    • Jingliang Wu
    • Siwei Liu
    • Ke Song
    • Guixiang Tian
  • View Affiliations

  • Published online on: June 9, 2023     https://doi.org/10.3892/mmr.2023.13029
  • Article Number: 142
  • Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

All‑trans retinoic acid (ATRA) has been implicated in the differentiation of hepatic stellate cells (HSCs). In the present study, the liver‑targeting hyaluronic acid micelles (ADHG) were prepared for co‑delivery of ATRA and doxorubicin (DOX) to block the HSC‑hepatoma interrelation. To simulate the tumor microenvironment, an in vitro dual‑cell model and an in vivo co‑implantation mouse model were established for anticancer studies. The experimental methods involved the MTT assay, wound‑healing assay, cellular uptake, flow cytometry and and in vivo antitumor study. The results revealed that the HSCs in the research models notably promoted tumor proliferation and migration. Furthermore, ADHG were readily internalized by cancer cells and HSCs simultaneously, and widely distributed in cancer regions. The in vivo antitumor studies demonstrated that ADHG could notably decrease HSC activation and extracellular matrix deposition, as well as constrain tumor growth and metastasis. Therefore, ATRA could facilitate DOX‑induced anti‑proliferation and anti‑metastasis effects, and ADHG are a promising nano‑sized formulation for the combination therapy of hepatocellular carcinoma.
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August-2023
Volume 28 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Lu Q, Gong X, Jia G, Wu J, Liu S, Song K and Tian G: A pH‑responsive hyaluronic acid nano‑vehicle co‑encapsulating doxorubicin and all‑trans retinoic acid for the inhibition of hepatic stellate cell‑induced tumor growth and metastasis. Mol Med Rep 28: 142, 2023
APA
Lu, Q., Gong, X., Jia, G., Wu, J., Liu, S., Song, K., & Tian, G. (2023). A pH‑responsive hyaluronic acid nano‑vehicle co‑encapsulating doxorubicin and all‑trans retinoic acid for the inhibition of hepatic stellate cell‑induced tumor growth and metastasis. Molecular Medicine Reports, 28, 142. https://doi.org/10.3892/mmr.2023.13029
MLA
Lu, Q., Gong, X., Jia, G., Wu, J., Liu, S., Song, K., Tian, G."A pH‑responsive hyaluronic acid nano‑vehicle co‑encapsulating doxorubicin and all‑trans retinoic acid for the inhibition of hepatic stellate cell‑induced tumor growth and metastasis". Molecular Medicine Reports 28.2 (2023): 142.
Chicago
Lu, Q., Gong, X., Jia, G., Wu, J., Liu, S., Song, K., Tian, G."A pH‑responsive hyaluronic acid nano‑vehicle co‑encapsulating doxorubicin and all‑trans retinoic acid for the inhibition of hepatic stellate cell‑induced tumor growth and metastasis". Molecular Medicine Reports 28, no. 2 (2023): 142. https://doi.org/10.3892/mmr.2023.13029