Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application to Injured Brain

Authors

Karthik Mouli
Anton V Liopo
Emily A McHugh
Erica Underwood
Jing Zhao
Pramod K Dash
Anh T T Vo
Vikas H Malojirao
Muralidhar L Hegde
James M Tour
Paul J Derry
Thomas A Kent

Publication Date

3-1-2025

Journal

Advanced Healthcare Materials

Abstract

Pro-energetic effects of functionalized, oxidized carbon nanozymes (OCNs) are reported. OCNs, derived from harsh acid oxidation of single-wall carbon nanotubes or activated charcoal are previously shown to possess multiple nanozymatic activities including mimicking superoxide dismutase and catalyzing the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to NAD+. These actions are predicted to generate a glycolytic shift and enhance mitochondrial energetics under impaired conditions. Impaired mitochondrial energy metabolism is increasingly recognized as an important facet of traumatic brain injury (TBI) pathophysiology and decreases the efficiency of electron transport chain (ETC)-coupled adenosine triphosphate (ATP) and NAD+ regeneration. In vitro, OCNs promote a pro-aerobic shift in energy metabolism that persists through ETC inhibition and enhances glycolytic flux, glycolytic ATP production, and cellular generation of lactate, a crucial auxiliary substrate for energy metabolism. To address specific mechanisms of iron injury from hemorrhage, OCNs with the iron chelator, deferoxamine (DEF), covalently-linked were synthesized. DEF-linked OCNs induce a glycolytic shift in-vitro and in-vivo in tissue sections from a rat model of TBI complicated by hemorrhagic contusion. OCNs further reduced hemorrhage volumes 3 days following TBI. These results suggest OCNs are promising as pleiotropic mediators of cell and tissue resilience to injury.

Keywords

Animals, Rats, Energy Metabolism, Oxidation-Reduction, Rats, Sprague-Dawley, Brain Injuries, Traumatic, Male, Nanotubes, Carbon, Carbon, Nanoparticles, Deferoxamine, Glycolysis, NAD, Mitochondria, Adenosine Triphosphate, bioenergetics, lactate, Mitochondria, Oxidized carbon nanozyme, traumatic brain injury

DOI

10.1002/adhm.202401629

PMID

39329414

PMCID

PMC11937864

PubMedCentral® Posted Date

9-27-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes