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Nanoparticle targeting to neurons in a rat hippocampal slice culture model

Academic Article
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Overview

authors

  • Walters, R.
  • Kraig, R. P.
  • Medintz, I.
  • Delehanty, J. B.
  • Stewart, M. H.
  • Susumu, K.
  • Huston, A. L.
  • Dawson, Philip
  • Dawson, G.

publication date

  • 2012

journal

  • ASN Neuro  Journal

abstract

  • We have previously shown that CdSe/ZnS core/shell luminescent semiconductor nanocrystals or QDs (quantum dots) coated with PEG [poly(ethylene glycol)]-appended DHLA (dihydrolipoic acid) can bind AcWG(Pal)VKIKKP(9)GGH(6) (Palm1) through the histidine residues. The coating on the QD provides colloidal stability and this peptide complex uniquely allows the QDs to be taken up by cultured cells and readily exit the endosome into the soma. We now show that use of a polyampholyte coating [in which the neutral PEG is replaced by the negatively heterocharged CL4 (compact ligand)], results in the specific targeting of the palmitoylated peptide to neurons in mature rat hippocampal slice cultures. There was no noticeable uptake by astrocytes, oligodendrocytes or microglia (identified by immunocytochemistry), demonstrating neuronal specificity to the overall negatively charged CL4 coating. In addition, EM (electron microscopy) images confirm the endosomal egress ability of the Palm1 peptide by showing a much more disperse cytosolic distribution of the CL4 QDs conjugated to Palm1 compared with CL4 QDs alone. This suggests a novel and robust way of delivering neurotherapeutics to neurons.

subject areas

  • Animals
  • Animals, Newborn
  • Drug Delivery Systems
  • Endosomes
  • Excitatory Amino Acid Agonists
  • Hippocampus
  • Luminescence
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • N-Methylaspartate
  • Neurons
  • Organ Culture Techniques
  • Peptides
  • Phosphopyruvate Hydratase
  • Polyethylene Glycols
  • Quantum Dots
  • Rats
  • Rats, Wistar
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Research

keywords

  • cell targeting
  • drug delivery
  • nanoparticle
  • neuronal uptake
  • pyramidal neuron
  • quantum dot
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Identity

PubMed Central ID

  • PMC3479791

International Standard Serial Number (ISSN)

  • 1759-0914

Digital Object Identifier (DOI)

  • 10.1042/an20120042

PubMed ID

  • 22973864
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Additional Document Info

start page

  • e00099

volume

  • 4

issue

  • 6

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