Development of electrochemical nanoprobe for real-time intracellular measurements of Fe2+ during ferroptosis

Abstract Ferroptosis is an iron-dependent form of regulated cell death driven by phospholipid peroxidation and the accumulation of reactive oxygen species (ROS), holding significant importance for therapeutic applications via its induction or inhibition. Accurate detection of intracellular Fe2+ and...

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Main Authors: Yanmei Ma, Xinhao Li, Weikang Hu, Muyang Ruan, Ming Yang, Lingqian Chang, Hongri Gu, Chengzhi Hu
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:Microsystems & Nanoengineering
Online Access:https://doi.org/10.1038/s41378-025-00930-6
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author Yanmei Ma
Xinhao Li
Weikang Hu
Muyang Ruan
Ming Yang
Lingqian Chang
Hongri Gu
Chengzhi Hu
author_facet Yanmei Ma
Xinhao Li
Weikang Hu
Muyang Ruan
Ming Yang
Lingqian Chang
Hongri Gu
Chengzhi Hu
author_sort Yanmei Ma
collection DOAJ
description Abstract Ferroptosis is an iron-dependent form of regulated cell death driven by phospholipid peroxidation and the accumulation of reactive oxygen species (ROS), holding significant importance for therapeutic applications via its induction or inhibition. Accurate detection of intracellular Fe2+ and ROS is essential, as these molecules play essential roles in initiating and propagating ferroptosis. In this study, we present a novel electrochemical nanoprobe for real-time, highly selective detection of intracellular Fe2+. The nanoprobes are prepared by coating gold nanoparticles (AuNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT) onto silicon carbide nanowires (SiC NWs), which are subsequently functionalized with ferrocenyl endoperoxide carboxylic acid (FDCA) and integrated with a liquid metal-filled glass nanopipette. FDCA is specifically synthesized to enable precise electrochemical detection of Fe2+ with high selectivity (0.1 nM to 1 µM) and exceptional specificity. PEDOT and AuNPs can improve electrical conductivity and provide a versatile interface for further FDCA decoration. We use the nanoprobes to evaluate the intracellular change of Fe2+ in MCF-7 breast cancer cells during erastin-induced ferroptosis. We observe a significant increase in intracellular Fe2+ levels in MCF-7 cells undergoing ferroptosis, accompanied by a notable rise in ROS levels. These findings underscore the potential of this nanoprobe to enhance our understanding of the mechanism of ferroptosis in tumor development and as a potential treatment target.
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spelling doaj-art-e1c73c61318641b38f27a6d8b0eef3ea2025-08-20T03:46:03ZengNature Publishing GroupMicrosystems & Nanoengineering2055-74342025-07-0111111010.1038/s41378-025-00930-6Development of electrochemical nanoprobe for real-time intracellular measurements of Fe2+ during ferroptosisYanmei Ma0Xinhao Li1Weikang Hu2Muyang Ruan3Ming Yang4Lingqian Chang5Hongri Gu6Chengzhi Hu7Shenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and TechnologyShenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and TechnologyShenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and TechnologyShenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and TechnologyShenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and TechnologyBeijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang UniversityDivision of Integrative Systems and Design, Hong Kong University of Science and TechnologyShenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and TechnologyAbstract Ferroptosis is an iron-dependent form of regulated cell death driven by phospholipid peroxidation and the accumulation of reactive oxygen species (ROS), holding significant importance for therapeutic applications via its induction or inhibition. Accurate detection of intracellular Fe2+ and ROS is essential, as these molecules play essential roles in initiating and propagating ferroptosis. In this study, we present a novel electrochemical nanoprobe for real-time, highly selective detection of intracellular Fe2+. The nanoprobes are prepared by coating gold nanoparticles (AuNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT) onto silicon carbide nanowires (SiC NWs), which are subsequently functionalized with ferrocenyl endoperoxide carboxylic acid (FDCA) and integrated with a liquid metal-filled glass nanopipette. FDCA is specifically synthesized to enable precise electrochemical detection of Fe2+ with high selectivity (0.1 nM to 1 µM) and exceptional specificity. PEDOT and AuNPs can improve electrical conductivity and provide a versatile interface for further FDCA decoration. We use the nanoprobes to evaluate the intracellular change of Fe2+ in MCF-7 breast cancer cells during erastin-induced ferroptosis. We observe a significant increase in intracellular Fe2+ levels in MCF-7 cells undergoing ferroptosis, accompanied by a notable rise in ROS levels. These findings underscore the potential of this nanoprobe to enhance our understanding of the mechanism of ferroptosis in tumor development and as a potential treatment target.https://doi.org/10.1038/s41378-025-00930-6
spellingShingle Yanmei Ma
Xinhao Li
Weikang Hu
Muyang Ruan
Ming Yang
Lingqian Chang
Hongri Gu
Chengzhi Hu
Development of electrochemical nanoprobe for real-time intracellular measurements of Fe2+ during ferroptosis
Microsystems & Nanoengineering
title Development of electrochemical nanoprobe for real-time intracellular measurements of Fe2+ during ferroptosis
title_full Development of electrochemical nanoprobe for real-time intracellular measurements of Fe2+ during ferroptosis
title_fullStr Development of electrochemical nanoprobe for real-time intracellular measurements of Fe2+ during ferroptosis
title_full_unstemmed Development of electrochemical nanoprobe for real-time intracellular measurements of Fe2+ during ferroptosis
title_short Development of electrochemical nanoprobe for real-time intracellular measurements of Fe2+ during ferroptosis
title_sort development of electrochemical nanoprobe for real time intracellular measurements of fe2 during ferroptosis
url https://doi.org/10.1038/s41378-025-00930-6
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