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ASN Neuro. 2012; 4(6): e00099.
Published online Oct 23, 2012. Prepublished online Sep 13, 2012. doi:  10.1042/AN20120042
PMCID: PMC3479791
Nanoparticle targeting to neurons in a rat hippocampal slice culture model
Ryan Walters,* Richard P Kraig,* Igor Medintz, James B Delehanty, Michael H Stewart,§ Kimihiro Susumu,§ Alan L Huston,§ Philip E Dawson, and Glyn Dawson* 1
*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.
§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.
1To whom correspondence should be addressed (email dawg/at/uchicago.edu).
Received June 14, 2012; Revised August 23, 2012; Accepted August 31, 2012.
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)VKIKKP9GGH6 (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.
Keywords: cell targeting, drug delivery, nanoparticle, neuronal uptake, pyramidal neuron, quantum dot
Abbreviations: CL4, compact ligand; CNS, central nervous system; CPP, cell-penetrating peptide; DAPI, 4′,6-diamidino-2-phenylindole; DHLA, dihydrolipoic acid; EM, electron microscopy; ER, endoplasmic reticulum; GFAP, glial fibrillary acidic protein; HEK-293, human embryonic kidney 293 cell; NeuN, neuron-specific nuclear protein; PEG, polyethylene glycol; PPT1, palmitoyl:protein thioesterase 1; QD, quantum dot
Articles from ASN NEURO are provided here courtesy of
American Society for Neurochemistry