Nanoparticle Targeting to Neurons in a Rat Hippocampal Slice Culture Model
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...
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2012-09-01
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Series: | ASN Neuro |
Online Access: | https://doi.org/10.1042/AN20120042 |
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doaj-4de718887d8044bb8c401ecc2742bc062020-11-25T03:26:30ZengSAGE PublishingASN Neuro1759-09141759-90912012-09-01410.1042/AN2012004210.1042_AN20120042Nanoparticle Targeting to Neurons in a Rat Hippocampal Slice Culture ModelRyan Walters0Richard P Kraig1Igor Medintz2James B Delehanty3Michael H Stewart4Kimihiro Susumu5Alan L Huston6Philip E Dawson7Glyn Dawson8 Committee on Neurobiology, University of Chicago, Chicago, IL 60637, U.S.A. Department of Neurology, University of Chicago, Chicago, IL 60637, U.S.A. Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375, U.S.A. Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375, U.S.A. Optical Sciences Division, Code 5611, U.S. Naval Research Laboratory, Washington, DC 20375, U.S.A. Optical Sciences Division, Code 5611, U.S. Naval Research Laboratory, Washington, DC 20375, U.S.A. Optical Sciences Division, Code 5611, U.S. Naval Research Laboratory, Washington, DC 20375, U.S.A. Scripps Research Institute, La Jolla, CA 92037, U.S.A. Departments of Pediatrics, Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, U.S.A.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.https://doi.org/10.1042/AN20120042 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ryan Walters Richard P Kraig Igor Medintz James B Delehanty Michael H Stewart Kimihiro Susumu Alan L Huston Philip E Dawson Glyn Dawson |
spellingShingle |
Ryan Walters Richard P Kraig Igor Medintz James B Delehanty Michael H Stewart Kimihiro Susumu Alan L Huston Philip E Dawson Glyn Dawson Nanoparticle Targeting to Neurons in a Rat Hippocampal Slice Culture Model ASN Neuro |
author_facet |
Ryan Walters Richard P Kraig Igor Medintz James B Delehanty Michael H Stewart Kimihiro Susumu Alan L Huston Philip E Dawson Glyn Dawson |
author_sort |
Ryan Walters |
title |
Nanoparticle Targeting to Neurons in a Rat Hippocampal Slice Culture Model |
title_short |
Nanoparticle Targeting to Neurons in a Rat Hippocampal Slice Culture Model |
title_full |
Nanoparticle Targeting to Neurons in a Rat Hippocampal Slice Culture Model |
title_fullStr |
Nanoparticle Targeting to Neurons in a Rat Hippocampal Slice Culture Model |
title_full_unstemmed |
Nanoparticle Targeting to Neurons in a Rat Hippocampal Slice Culture Model |
title_sort |
nanoparticle targeting to neurons in a rat hippocampal slice culture model |
publisher |
SAGE Publishing |
series |
ASN Neuro |
issn |
1759-0914 1759-9091 |
publishDate |
2012-09-01 |
description |
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. |
url |
https://doi.org/10.1042/AN20120042 |
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