期刊
ASN NEURO
卷 4, 期 6, 页码 -出版社
SAGE PUBLICATIONS LTD
DOI: 10.1042/AN20120042
关键词
cell targeting; drug delivery; nanoparticle; neuronal uptake; pyramidal neuron; quantum dot
资金
- USPHS (United States Public Health Service) [NS36866-38, NS-19108]
- P50 Grant [HD09402]
- Childrens Brain Disease Foundation
- NRL (Naval Research Laboratory)
- NRL NSI (Naval Research Laboratory Nanoscience Institute)
- ONR (Office of Naval Research)
- DARPA (Defense Advanced Research Project Agency)
- DTRA (Defense Threat Research Agency) JSTO (Joint Science and Technology Office) MIPR (Military Interdepartmental Purchase Request) [B112582M]
- [GM098871]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [P01HD009402] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM098871] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS019108, R01NS036866] Funding Source: NIH RePORTER
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.
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