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Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application to Injured Brain.

Karthik Mouli1, Anton V Liopo1,2, Emily A McHugh2,3

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Oxidized carbon nanozymes (OCNs) enhance cellular energy production, boosting glycolysis and ATP generation. These nanozymes show promise in mitigating traumatic brain injury complications and reducing hemorrhage.

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Area of Science:

  • Biomaterials Science
  • Neuroscience
  • Biochemistry

Background:

  • Impaired mitochondrial energy metabolism is a key factor in traumatic brain injury (TBI) pathophysiology.
  • This impairment reduces the efficiency of electron transport chain (ETC)-coupled adenosine triphosphate (ATP) and NAD+ regeneration.
  • Oxidized carbon nanozymes (OCNs) exhibit nanozymatic activities, including superoxide dismutase mimicry and NADH oxidation.

Purpose of the Study:

  • To investigate the pro-energetic effects of OCNs on cellular metabolism, particularly under conditions mimicking TBI.
  • To explore the potential of OCNs, functionalized with an iron chelator (deferoxamine, DEF), in addressing iron-related injury in TBI with hemorrhage.
  • To evaluate the in vitro and in vivo efficacy of OCNs in improving energy metabolism and reducing injury severity.

Main Methods:

  • OCNs were synthesized via harsh acid oxidation of carbon nanotubes or activated charcoal.
  • In vitro studies assessed OCNs' effects on glycolytic flux, ATP production, and NAD+ regeneration, including under ETC inhibition.
  • DEF-linked OCNs were synthesized and tested in vitro and in vivo using a rat model of TBI with hemorrhagic contusion.

Main Results:

  • OCNs promoted a pro-aerobic shift in energy metabolism, enhancing glycolytic flux and ATP production.
  • This pro-energetic effect persisted even with ETC inhibition.
  • DEF-linked OCNs induced a glycolytic shift in vitro and in vivo, and OCNs reduced hemorrhage volumes in a TBI model.

Conclusions:

  • OCNs demonstrate significant pro-energetic effects by enhancing glycolysis and cellular ATP generation.
  • Functionalized OCNs show potential in mitigating TBI complications, including hemorrhage.
  • OCNs represent promising pleiotropic mediators for enhancing cell and tissue resilience to injury.