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Therapeutic impacts of GNE‑477‑loaded H2O2 stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma

  • Authors:
    • Songmu Pan
    • Zhuan Zou
    • Xiaofeng Zhou
    • Jiyong Wei
    • Huijiang Liu
    • Zhongyi Su
    • Gui Liao
    • Guangyu Huang
    • Zonggui Huang
    • Yi Xu
    • Minan Lu
    • Ronghe Gu
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, The First People's Hospital of Nanning, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530022, P.R. China, Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Orthopedic Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
    Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 69
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    Published online on: June 27, 2024
       https://doi.org/10.3892/ijmm.2024.5393
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Abstract

Osteosarcoma (OS) is a highly malignant primary bone neoplasm that is the leading cause of cancer‑associated death in young people. GNE‑477 belongs to the second generation of mTOR inhibitors and possesses promising potential in the treatment of OS but dose tolerance and drug toxicity limit its development and utilization. The present study aimed to prepare a novel H2O2 stimulus‑responsive dodecanoic acid (DA)‑phenylborate ester‑dextran (DA‑B‑DEX) polymeric micelle delivery system for GNE‑477 and evaluate its efficacy. The polymer micelles were characterized by morphology, size and critical micelle concentration. The GNE‑477 loaded DA‑B‑DEX (GNE‑477@DBD) tumor‑targeting drug delivery system was established and the release of GNE‑477 was measured. The cellular uptake of GNE‑477@DBD by three OS cell lines (MG‑63, U2OS and 143B cells) was analyzed utilizing a fluorescent tracer technique. The hydroxylated DA‑B was successfully grafted onto dextran at a grafting rate of 3%, suitable for forming amphiphilic micelles. Following exposure to H2O2, the DA‑B‑DEX micelles ruptured and released the drug rapidly, leading to increased uptake of GNE‑477@DBD by cells with sustained release of GNE‑477. The in vitro experiments, including MTT assay, flow cytometry, western blotting and RT‑qPCR, demonstrated that GNE‑477@DBD inhibited tumor cell viability, arrested cell cycle in G1 phase, induced apoptosis and blocked the PI3K/Akt/mTOR cascade response. In vivo, through the observation of mice tumor growth and the results of H&E staining, the GNE‑477@DBD group exhibited more positive therapeutic outcomes than the free drug group with almost no adverse effects on other organs. In conclusion, H2O2‑responsive DA‑B‑DEX presents a promising delivery system for hydrophobic anti‑tumor drugs for OS therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Pan S, Zou Z, Zhou X, Wei J, Liu H, Su Z, Liao G, Huang G, Huang Z, Xu Y, Xu Y, et al: Therapeutic impacts of GNE‑477‑loaded H<sub>2</sub>O<sub>2</sub> stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma. Int J Mol Med 54: 69, 2024.
APA
Pan, S., Zou, Z., Zhou, X., Wei, J., Liu, H., Su, Z. ... Gu, R. (2024). Therapeutic impacts of GNE‑477‑loaded H<sub>2</sub>O<sub>2</sub> stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma. International Journal of Molecular Medicine, 54, 69. https://doi.org/10.3892/ijmm.2024.5393
MLA
Pan, S., Zou, Z., Zhou, X., Wei, J., Liu, H., Su, Z., Liao, G., Huang, G., Huang, Z., Xu, Y., Lu, M., Gu, R."Therapeutic impacts of GNE‑477‑loaded H<sub>2</sub>O<sub>2</sub> stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma". International Journal of Molecular Medicine 54.2 (2024): 69.
Chicago
Pan, S., Zou, Z., Zhou, X., Wei, J., Liu, H., Su, Z., Liao, G., Huang, G., Huang, Z., Xu, Y., Lu, M., Gu, R."Therapeutic impacts of GNE‑477‑loaded H<sub>2</sub>O<sub>2</sub> stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma". International Journal of Molecular Medicine 54, no. 2 (2024): 69. https://doi.org/10.3892/ijmm.2024.5393
Copy and paste a formatted citation
x
Spandidos Publications style
Pan S, Zou Z, Zhou X, Wei J, Liu H, Su Z, Liao G, Huang G, Huang Z, Xu Y, Xu Y, et al: Therapeutic impacts of GNE‑477‑loaded H<sub>2</sub>O<sub>2</sub> stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma. Int J Mol Med 54: 69, 2024.
APA
Pan, S., Zou, Z., Zhou, X., Wei, J., Liu, H., Su, Z. ... Gu, R. (2024). Therapeutic impacts of GNE‑477‑loaded H<sub>2</sub>O<sub>2</sub> stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma. International Journal of Molecular Medicine, 54, 69. https://doi.org/10.3892/ijmm.2024.5393
MLA
Pan, S., Zou, Z., Zhou, X., Wei, J., Liu, H., Su, Z., Liao, G., Huang, G., Huang, Z., Xu, Y., Lu, M., Gu, R."Therapeutic impacts of GNE‑477‑loaded H<sub>2</sub>O<sub>2</sub> stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma". International Journal of Molecular Medicine 54.2 (2024): 69.
Chicago
Pan, S., Zou, Z., Zhou, X., Wei, J., Liu, H., Su, Z., Liao, G., Huang, G., Huang, Z., Xu, Y., Lu, M., Gu, R."Therapeutic impacts of GNE‑477‑loaded H<sub>2</sub>O<sub>2</sub> stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma". International Journal of Molecular Medicine 54, no. 2 (2024): 69. https://doi.org/10.3892/ijmm.2024.5393
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