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Nicotinamide-Loaded Peptoid Nanotubes for Energy Regeneration in Acute Brain Injury
Hui Du1, Thi Kim Hoang Trinh2, Olivia C Brandon3
1Department of Chemical Engineering, University of Washington, Seattle Washington 98195, United States.
ACS Nano
|April 13, 2026
Summary
New nanopeptoid nanotubes deliver nicotinamide (NAM) to brain cells, restoring energy and reducing damage after acute brain injury. This targeted approach improves cell viability and neuropathology in preclinical models.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Nanotechnology
Background:
- Acute brain injuries cause energy depletion and inflammation, hindering recovery.
- Nicotinamide adenine dinucleotide (NAD+) is vital for ATP regeneration and DNA repair.
- Effective cell-specific delivery of NAD+ precursors like nicotinamide (NAM) remains a challenge.
Purpose of the Study:
- To develop a nanopeptoid delivery system for targeted intracellular delivery of NAM.
- To investigate the therapeutic potential of NAM-conjugated peptoid nanotubes (NAM-PNTs) in acute brain injury models.
Main Methods:
- Self-assembly of peptoids into NAM-conjugated nanotubes (NAM-PNTs).
- In vitro testing on oxygen-glucose-deprived (OGD) BV-2 cells and organotypic brain slices.
- In vivo studies using term-equivalent rats subjected to hypoxia-ischemia.
Main Results:
- NAM-PNTs enhanced cell viability and replenished ATP levels in OGD BV-2 cells within 24 hours.
- Treatment reduced proinflammatory cytokines and increased anti-inflammatory cytokines in OGD brain slices.
- Systemic NAM-PNT administration localized to microglia in the injured hemisphere, reducing tissue loss and improving neuropathology in rats.
Conclusions:
- NAM-PNTs offer a promising strategy for cell-specific targeted delivery of NAM to restore energy in the acutely injured brain.
- This nanopeptoid platform demonstrates potential for treating neonatal brain injuries.
- The study showcases a comprehensive development pipeline from nanoparticle design to in vivo efficacy.
