Open Access

Development of a cancer cells self‑activating and miR‑125a‑5p expressing poly‑pharmacological nanodrug for cancer treatment

  • Authors:
    • Yung-Chieh Chang
    • Min-Chieh Shieh
    • Yen-Hsuan Chang
    • Wei-Lun Huang
    • Wu-Chou Su
    • Fong-Yu Cheng
    • Chun Hei Antonio Cheung
  • View Affiliations

  • Published online on: June 14, 2022     https://doi.org/10.3892/ijmm.2022.5158
  • Article Number: 102
  • Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cancer cells can acquire resistance to targeted therapeutic agents when the designated targets or their downstream signaling molecules develop protein conformational or activity changes. There is an increasing interest in developing poly‑pharmacologic anticancer agents to target multiple oncoproteins or signaling pathways in cancer cells. The microRNA 125a‑5p (miR‑125a‑5p) is a tumor suppressor, and its expression has frequently been downregulated in tumors. By contrast, the anti‑apoptotic molecule BIRC5/SURVIVIN is highly expressed in tumors but not in the differentiated normal tissues. In the present study, the development of a BIRC5 gene promoter‑driven, miR‑125a‑5p expressing, poly‑L‑lysine‑conjugated magnetite iron poly‑pharmacologic nanodrug (pL‑MNP‑pSur‑125a) was reported. The cancer cells self‑activating property and the anticancer effects of this nanodrug were examined in both the multidrug efflux protein ABCB1/MDR1‑expressing/‑non‑expressing cancer cells in vitro and in vivo. It was demonstrated that pL‑MNP‑pSur‑125a decreased the expression of ERBB2/HER2, HDAC5, BIRC5, and SP1, which are hot therapeutic targets for cancer in vitro. Notably, pL‑MNP‑pSur‑125a also downregulated the expression of TDO2 in the human KB cervical carcinoma cells. PL‑MNP‑pSur‑125a decreased the viability of various BIRC5‑expressing cancer cells, regardless of the tissue origin or the expression of ABCB1, but not of the human BIRC5‑non‑expressing HMEC‑1 endothelial cells. In vivo, pL‑MNP‑pSur‑125a exhibited potent antitumor growth effects, but without inducing liver toxicity, in various zebrafish human‑ABCB1‑expressing and ABCB1‑non‑expressing tumor xenograft models. In conclusion, pL‑MNP‑pSur‑125a is an easy‑to‑prepare and a promising poly‑pharmacological anticancer nanodrug that has the potential to manage numerous malignancies, particularly for patients with BIRC5/ABCB1‑related drug resistance after prolonged chemotherapeutic treatments.
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August-2022
Volume 50 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chang Y, Shieh M, Chang Y, Huang W, Su W, Cheng F and Cheung CA: Development of a cancer cells self‑activating and miR‑125a‑5p expressing poly‑pharmacological nanodrug for cancer treatment. Int J Mol Med 50: 102, 2022
APA
Chang, Y., Shieh, M., Chang, Y., Huang, W., Su, W., Cheng, F., & Cheung, C.A. (2022). Development of a cancer cells self‑activating and miR‑125a‑5p expressing poly‑pharmacological nanodrug for cancer treatment. International Journal of Molecular Medicine, 50, 102. https://doi.org/10.3892/ijmm.2022.5158
MLA
Chang, Y., Shieh, M., Chang, Y., Huang, W., Su, W., Cheng, F., Cheung, C. A."Development of a cancer cells self‑activating and miR‑125a‑5p expressing poly‑pharmacological nanodrug for cancer treatment". International Journal of Molecular Medicine 50.2 (2022): 102.
Chicago
Chang, Y., Shieh, M., Chang, Y., Huang, W., Su, W., Cheng, F., Cheung, C. A."Development of a cancer cells self‑activating and miR‑125a‑5p expressing poly‑pharmacological nanodrug for cancer treatment". International Journal of Molecular Medicine 50, no. 2 (2022): 102. https://doi.org/10.3892/ijmm.2022.5158