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During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
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The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
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Enhancing ROS-Inducing Nanozyme through Intraparticle Electron Transport.

Zhongchao Yi1, Xiaoyue Yang1, Ying Liang2

  • 1F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY, 40536, USA.

Small (Weinheim an Der Bergstrasse, Germany)
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Summary

Wüstite (FeO) nanoparticles show superior Fenton catalytic activity for reactive oxygen species (ROS) generation compared to other iron oxide nanoparticles. This discovery enhances the potential of ROS-dependent disease treatments using nanozymes.

Keywords:
Fenton reactioniron oxide nanoparticlesreactive oxygen specieswüstite nanoparticles

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Area of Science:

  • Nanotechnology
  • Materials Science
  • Biomedical Engineering

Background:

  • Iron oxide nanoparticles (IONPs) are promising for reactive oxygen species (ROS)-dependent disease treatment due to biocompatibility and Fenton catalytic activity.
  • Low catalytic activity of current IONPs hinders clinical translation for effective ROS-dependent therapies.

Purpose of the Study:

  • To investigate and enhance the Fenton catalytic activity of different iron oxide nanoparticle compositions for improved ROS generation.
  • To identify the mechanism behind the enhanced catalytic activity of specific IONPs for therapeutic applications.

Main Methods:

  • Synthesis and characterization of wüstite (FeO), magnetite (Fe3O4), and maghemite (γ-Fe2O3) nanoparticles.
  • Evaluation of Fenton reaction kinetics under pharmacologically relevant conditions.
  • Analysis of intraparticle electron transport mechanisms and ROS generation in cancer cells.

Main Results:

  • Wüstite (FeO) nanoparticles demonstrated significantly higher Fenton catalytic activity compared to magnetite and maghemite nanoparticles of similar size and coating.
  • The enhanced activity of wüstite is attributed to internal low-valence iron (Fe0 and Fe2+) facilitating efficient Fe3+/Fe2+ recycling via intraparticle electron transport.
  • Ultrasmall wüstite nanoparticles exhibited a 5.3-fold higher Fenton reaction rate than ferumoxytol, increasing intracellular ROS levels in mouse mammary carcinoma cells.

Conclusions:

  • Wüstite (FeO) nanoparticles represent a novel, highly efficient nanozyme platform for ROS generation, overcoming limitations of existing IONPs.
  • The findings present a new mechanism for enhancing nanozyme catalytic activity and offer significant improvements for developing advanced ROS-inducing therapeutics.
  • This study expands the therapeutic potential of nanozymes for ROS-dependent diseases.