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<p>Copper cytotoxicity provides a viable way to fight microbial infections and cancer. While it is generally known that redox homeostasis in the mitochondria critically affects copper cytotoxicity, its precise impact remains elusive due to the lack of suitable characterization techniques. Here, we designed a multifunctional plasmonic nanosensor and propose the concept of a redox index, which combined allow dynamic real-time monitoring of the mitochondrial redox state during copper-induced cell death via surface-enhanced Raman spectroscopy. This revealed significant redox swings throughout the cell death process and showed that reactive oxygen species (ROS) significantly elevated copper cytotoxicity. This understanding offers insight into the design of combinatorial therapeutic strategies. For example, we showed that the addition of micromolars of external ROS stimulants improved copper-based cancer treatment efficacy by &gt;6 times. Beyond biological applications, we envisage that our nanosensor will become a useful tool for a wide range of applications based on redox chemistry.</p>

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Direct visualization of mitochondrial redox states via redox index-assisted surface-enhanced Raman spectroscopy enables improved copper-based cancer therapy

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Chengye Xi,
  • Yi Wang,
  • Junjie Yu,
  • Shiyi Zhang,
  • Hanbin Xu,
  • Yue He,
  • Sining Wang,
  • Huaying Chen,
  • Yikai Xu,
  • Dawei Li

摘要

Copper cytotoxicity provides a viable way to fight microbial infections and cancer. While it is generally known that redox homeostasis in the mitochondria critically affects copper cytotoxicity, its precise impact remains elusive due to the lack of suitable characterization techniques. Here, we designed a multifunctional plasmonic nanosensor and propose the concept of a redox index, which combined allow dynamic real-time monitoring of the mitochondrial redox state during copper-induced cell death via surface-enhanced Raman spectroscopy. This revealed significant redox swings throughout the cell death process and showed that reactive oxygen species (ROS) significantly elevated copper cytotoxicity. This understanding offers insight into the design of combinatorial therapeutic strategies. For example, we showed that the addition of micromolars of external ROS stimulants improved copper-based cancer treatment efficacy by >6 times. Beyond biological applications, we envisage that our nanosensor will become a useful tool for a wide range of applications based on redox chemistry.