Assessment of zero-valent iron-based nanotherapeutics for ferroptosis induction and resensitization strategy in cancer cells

Kuang Jing Huang, Yau Huei Wei, Yen Chi Chiu, Shang Rung Wu, Dar Bin Shieh

研究成果: Article同行評審

20 引文 斯高帕斯(Scopus)

摘要

Addressing nanomedicine resistance is critical for its ultimate clinical success; despite this, advancing .the therapeutic designs for cancer therapy are rarely discussed in the literature. In this study, we discovered that ferroptosis is the central mechanism governing the therapeutic efficacy and resistance of treatment with zero-valent iron nanoparticles (ZVI NPs). In ZVI-sensitive oral cancer cells, ZVI NPs-induced ferroptosis was characterized by mitochondrial lipid peroxidation and reduced levels of glutathione peroxidases (GPx) in subcellular organelles. However, resistant cells could attenuate ZVI-induced oxidative stress and GPx reduction. They also showed stronger mitochondrial respiration ability, thus resisting ZVI NPs-induced mitochondrial membrane potential loss. Transcriptome comparison and quantitative polymerase chain reaction (qPCR) analysis revealed that ZVI-resistant cancer cells expressed a gene set related to enhanced NADPH supply, higher detoxification capacity of reactive oxygen species, and decreased sensitivity to ferroptosis inducers (FINs). Finally, we discovered that certain FINs were able to sensitize ZVI-resistant cancer cells to become treatable without compromising healthy non-malignant cells. These findings suggest that ferroptosis can serve as a druggable target for anti-cancer nanomedicine and therapeutic resistance modulation using ZVI NPs.

原文English
頁(從 - 到)1311-1322
頁數12
期刊Biomaterials Science
7
發行號4
DOIs
出版狀態Published - 2019 四月

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Materials Science(all)

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