Open Access

Iron oxide nanoparticles induce ferroptosis via the autophagic pathway by synergistic bundling with paclitaxel

  • Authors:
    • Qi Nie
    • Wenqing Chen
    • Tianmei Zhang
    • Shangrong Ye
    • Zhongyu Ren
    • Peng Zhang
    • Jian Wen
  • View Affiliations

  • Published online on: September 6, 2023     https://doi.org/10.3892/mmr.2023.13085
  • Article Number: 198
  • Copyright: © Nie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In recent years, inhibiting tumor cell activity by triggering cell ferroptosis has become a research hotspot. The development of generic targeted nanotherapeutics might bring new ideas for non‑invasive applications. Currently, the potential mechanism underlying the universal application of paclitaxel (PTX)‑loaded iron oxide nanoparticles (IONP@PTX) to different types of tumors is unclear. The present study aimed to prepare IONP@PTX for targeted cancer therapy and further explore the potential mechanisms underlying the inhibitory effects of this material on the NCI‑H446 human small cell lung cancer and brain M059K malignant glioblastoma cell lines. First, a CCK‑8 assay was performed to determine cell viability, and then the combination index for evaluating drug combination interaction effect was evaluated. Intracellular reactive oxygen species (ROS) and lipid peroxidation levels were monitored using a DCFH‑DA fluorescent probe and a C11‑BODIPY™ fluorescent probe, respectively. Furthermore, western blotting assay was performed to determine the expression of autophagy‑ and iron death‑related proteins. The experimental results showed that, compared with either IONP monotherapy, PTX monotherapy, or IONP + PTX, IONP@PTX exerted a synergistic effect on the viability of both cell types, with significantly increased total iron ion concentration, ROS levels and lipid peroxidation levels. IONP@PTX significantly increased the expression of autophagy‑related proteins Beclin 1 and histone deacetylase 6 (HDAC6) in both cell lines (P<0.05), increased the expression of light chain 3 (LC3)‑II/I in NCI‑H446 cells (P<0.05) and decreased that of sequestosome1 (p62) in M059K cells (P<0.05). Moreover, the addition of rapamycin enhanced the IONP@PTX‑induced the upregulation of Beclin 1, LC3‑II/I and HDAC6 and the downregulation of mTORC1 protein in both cell lines (P<0.05). Moreover, rapamycin enhanced the IONP@PTX‑induced downregulation of p62 protein in NCI‑H446 cells (P<0.05), suggesting that IONP@PTX induces ferroptosis, most likely through autophagy. Collectively, the present findings show that IONP works synergistically with PTX to induce ferroptosis via the autophagic pathway.
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October-2023
Volume 28 Issue 4

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

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Copy and paste a formatted citation
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Spandidos Publications style
Nie Q, Chen W, Zhang T, Ye S, Ren Z, Zhang P and Wen J: Iron oxide nanoparticles induce ferroptosis via the autophagic pathway by synergistic bundling with paclitaxel. Mol Med Rep 28: 198, 2023
APA
Nie, Q., Chen, W., Zhang, T., Ye, S., Ren, Z., Zhang, P., & Wen, J. (2023). Iron oxide nanoparticles induce ferroptosis via the autophagic pathway by synergistic bundling with paclitaxel. Molecular Medicine Reports, 28, 198. https://doi.org/10.3892/mmr.2023.13085
MLA
Nie, Q., Chen, W., Zhang, T., Ye, S., Ren, Z., Zhang, P., Wen, J."Iron oxide nanoparticles induce ferroptosis via the autophagic pathway by synergistic bundling with paclitaxel". Molecular Medicine Reports 28.4 (2023): 198.
Chicago
Nie, Q., Chen, W., Zhang, T., Ye, S., Ren, Z., Zhang, P., Wen, J."Iron oxide nanoparticles induce ferroptosis via the autophagic pathway by synergistic bundling with paclitaxel". Molecular Medicine Reports 28, no. 4 (2023): 198. https://doi.org/10.3892/mmr.2023.13085