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Neural Tracing Protein-Functionalized Nanoparticles Capable of Fast Retrograde Axonal Transport in Live Neurons.

Wenqian Wang1, Md Musfizur Hassan1, Natasha Kapoor-Kaushik2

  • 1School of Chemical Engineering, University of New South Wales (UNSW Sydney), Sydney, NSW, 2052, Australia.

Small (Weinheim an Der Bergstrasse, Germany)
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Researchers developed nanoparticle-based neural tracers that can bypass the blood-brain barrier (BBB) for central nervous system (CNS) drug delivery. Modified gold nanoparticles show enhanced transport in neurons, paving the way for new nanomedicines.

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axonal transportmicrofluidicsneural tracing proteinsingle‐particle trackingtwo‐photon confocal microscopy

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Area of Science:

  • Neuroscience
  • Nanotechnology
  • Biomedical Engineering

Background:

  • Neural tracing proteins like WGA-HRP facilitate CNS targeting via retrograde transport without breaching the blood-brain barrier (BBB).
  • Nanoparticle conjugation offers a potential strategy for developing BBB-bypassing nanomedicine for neurological disorders.

Purpose of the Study:

  • To screen nanocarriers for efficient neuronal transport and understand their mechanisms of action.
  • To investigate the impact of protein modification on nanoparticle uptake and axonal transport dynamics.
  • To develop a cell-based assay for evaluating neuron-targeted nanoparticles.

Main Methods:

  • Utilized microfluidics and two-photon confocal microscopy to analyze nanocarrier transport in neurons.
  • Modified gold nanoparticles with WGA-HRP and compared their axonal transport to nonconjugated nanoparticles.
  • Performed trajectory analysis of endosomes containing nanoparticles to quantify transport parameters.

Main Results:

  • Protein modification of gold nanoparticles enhanced cellular uptake at the axonal terminal and activated fast retrograde transport.
  • Endosomes carrying WGA-HRP-conjugated gold nanoparticles exhibited significantly longer run durations and faster instantaneous velocities compared to nonconjugated nanoparticles.
  • Mechanistic insights into axonal transport dynamics were elucidated, revealing differences based on nanoparticle conjugation.

Conclusions:

  • WGA-HRP-conjugated gold nanoparticles demonstrate improved axonal transport, suggesting potential for BBB-bypassing nanomedicine.
  • The developed cell-based assay provides a functional evaluation of neuron-targeted nanoparticles.
  • This research contributes to the development of novel therapeutic strategies for nervous system disorders.