Intracellular Quantum Sensing of Free-Radical Generation Induced by Acetaminophen (APAP) in the Cytosol, in Mitochondria and the Nucleus of Macrophages

Rokshana Sharmin, Anggrek C. Nusantara, Linyan Nie, Kaiqi Wu, Arturo Elias Llumbet, Willem Woudstra, Aldona Mzyk, Romana Schirhagl*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)
92 Downloads (Pure)

Abstract

Acetaminophen overdoses cause cell injury in the liver. It is widely accepted that liver toxicity is initiated by the reactive N-acetyl-para-aminophenol (APAP) metabolite N-acetyl-p-benzoquinone imine (NAPQI), which first depletes glutathione and then irreversibly binds to mitochondrial proteins and nuclear DNA. As a consequence, mitochondrial respiration is inhibited, and DNA strands break. NAPQI also promotes the oxidative stress since glutathione is one of the main free-radical scavengers in the cell. However, so far it is unknown where exactly free radicals are generated. In this study, we used relaxometry, a novel technique that allows nanoscale magnetic resonance imaging detection of free radicals. The method is based on fluorescent nanodiamonds, which change their optical properties based on their magnetic surrounding. To achieve subcellular resolution, these nanodiamonds were targeted to cellular locations, that is, the cytoplasm, mitochondria, and the nucleus. Since relaxometry is sensitive to spin noise from radicals, we were able to measure the radical load in these different organelles. For the first time, we measured APAP-induced free-radical production in an organelle-specific manner, which helps predict and better understand cellular toxicity.

Original languageEnglish
Pages (from-to)3326-3334
Number of pages9
JournalACS Sensors
Volume7
Issue number11
DOIs
Publication statusPublished - 10-Nov-2022

Keywords

  • cells
  • liver toxicity
  • nanodiamonds
  • NV centers
  • relaxometry

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