Fluorescently-tagged anti-ganglioside antibody selectively identifies peripheral nerve in living animals

Sci Rep. 2015 Oct 30:5:15766. doi: 10.1038/srep15766.

Abstract

Selective in vivo delivery of cargo to peripheral nervous system (PNS) has broad clinical and preclinical applications. An important applicability of this approach is systemic delivery of fluorescently conjugated ligands that selectively label PNS, which could allow visualization of peripheral nerves during any surgery. We examine the use of an anti-ganglioside monoclonal antibody (mAb) as selective neuronal delivery vector for surgical imaging of peripheral nerves. Systemic delivery of an anti-ganglioside mAb was used for selective intraneuronal/axonal delivery of fluorescent agents to visualize nerves by surgical imaging in living mice. In this study, we show that intact motor, sensory, and autonomic nerve fibers/paths are distinctly labeled following a single nanomolar systemic injection of fluorescently labeled anti-ganglioside mAb. Tissue biodistribution studies with radiolabeled mAb were used to validate neuronal uptake of fluorescently labeled mAb. Implications of this proof of concept study are that fluorescent conjugates of anti-ganglioside mAbs are valuable delivery vectors to visualize nerves during surgery to avoid nerve injury and monitor nerve degeneration and regeneration after injury. These findings support that antibodies, and their derivatives/fragments, can be used as selective neuronal delivery vector for transport of various cargos to PNS in preclinical and clinical settings.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Axons / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Fluorescent Dyes / chemistry
  • Gangliosides / immunology
  • Gangliosides / metabolism*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Nerve Degeneration / pathology
  • Peripheral Nerves / metabolism*
  • Radioisotopes / chemistry
  • Tissue Distribution
  • Zirconium / chemistry

Substances

  • Antibodies, Monoclonal
  • Bacterial Proteins
  • Fluorescent Dyes
  • Gangliosides
  • Luminescent Proteins
  • Radioisotopes
  • yellow fluorescent protein, Bacteria
  • Zirconium