Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury

Molecular Therapy, 2015 · DOI: 10.1038/mt.2015.50 · Published: June 1, 2015

Simple Explanation

The study investigates the potential of PEG-functionalized gold nanoparticles (PEG-AuNPs) to aid recovery after spinal cord injury (SCI) in mice. It addresses the challenge of limited regeneration in the central nervous system after injury. The researchers delivered PEG-AuNPs directly into the spinal cord of mice shortly after injury. They observed improvements in hind limb motor function, reduced inflammation, enhanced motor neuron survival, and increased myelination. The findings suggest that PEG-AuNPs can serve as a beneficial drug-delivery platform for treating SCI, potentially improving outcomes by minimizing acute phase damage and promoting nerve regeneration.

Study Duration

8 Weeks

Participants

C57BL/6J female mice

Evidence Level

Not specified

Key Findings

1
Intraspinal delivery of PEG-AuNP-40 improved hind limb motor function recovery in mice after spinal cord injury.
2
PEG-AuNP-40 treatment attenuated the inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown axons.
3
PEG-AuNP-40 promoted remyelination after injury, contributing to the restoration of conductivity in spared and/or regrown axons.

Research Summary

This study demonstrates that intraspinal administration of PEG-functionalized gold nanoparticles during the acute phase after spinal cord injury is beneficial in restoring hind limb motor function. The positive functional outcome was accompanied in cellular terms by an attenuated microglial/macrophage response, enhanced neuroprotection, and reformation of synapses after injury and increased remyelination. The overall beneficial effects of the PEG-functionalized colloidal gold nanoparticles used in this study are congruent with the membrane-sealing properties of PEG.

Practical Implications

Drug Delivery Platform

PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential for SCI treatment.

Acute Intervention

The study supports the relevance of immediate intervention after injury, suggesting PEG-AuNPs could be applied at the same time as early spinal decompression and stabilization surgery.

Combination Therapy

The nanocarrier system could be combined with biomolecular enhancers of regeneration for more effective clinical adaptation.

Study Limitations

1
The study did not gain evidence that improved functional recovery in the PEG-AuNP-40 group of mice could be ascribed to enhanced axonal sparing or regrowth despite the enhanced neurite outgrowth supported by PEG-AuNP-40 in in vitro, reflecting the complexity of the environment in vivo.
2
Additional control groups receiving either AuNP-14 or AuNP-40 without PEG coating, although desirable, could not be included in the study because uncoated citrate-stabilized AuNPs are incompatible with biological environments, both in vitro and in vivo due to their high tendency to aggregate and sediment.
3
We cannot exclude that differences in toxicity might also play a role.

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