Gewählte Publikation:
SHR
Neuro
Krebs
Kardio
Lipid
Stoffw
Microb
Siegemund, T; Paulke, BR; Schmiedel, H; Bordag, N; Hoffmann, A; Harkany, T; Tanila, H; Kacza, J; Härtig, W.
Thioflavins released from nanoparticles target fibrillar amyloid beta in the hippocampus of APP/PS1 transgenic mice.
Int J Dev Neurosci. 2006; 24(2-3):195-201
Doi: 10.1016/j.ijdevneu.2005.11.012
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
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Bordag Natalie
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- Abstract:
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For the delivery of drugs into the brain, the use of nanoparticles as carriers has been described as a promising approach. Here, we prepared nanoparticles as carriers for the model drugs thioflavin T and thioflavin S that bind fibrillar amyloid beta peptides (Abeta). These polymer colloids are composed of a polystyrene core and a degradable PBCA [poly(butyl-2-cyanoacrylate)] shell with a diameter of 90-100nm as shown by dynamic light scattering. Fluorescence spectrophotometric analysis revealed that encapsulated thioflavin T exhibited significantly stronger fluorescence than the free fluorophore. The enzymatic degradation of core-shell nanoparticles, as required in vivo, was shown after their treatment with porcine liver esterase, a non-specific esterase, in vitro. Shells of nanoparticles were dose-dependently degraded while their polystyrene cores remained intact. In the cortices of 7-14 months old APP/PS1 mice with age-dependent beta-amyloidosis, thioflavins selectively targeted fibrillar Abeta after biodegradation-induced release from their nanoparticulate carriers upon intracerebral injection. Collectively, our data suggest that core-shell nanoparticles with controlled degradation in vivo can become versatile tools to trace and clear Abeta in the brain.
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Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Alzheimer Disease - pathology
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Amyloid - metabolism
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Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism
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Animals -
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Disease Models, Animal -
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Dose-Response Relationship, Drug -
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Drug Delivery Systems -
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Hippocampus - drug effects Hippocampus - metabolism
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Mice -
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Mice, Transgenic -
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Nanostructures -
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Neurofibrillary Tangles - drug effects Neurofibrillary Tangles - metabolism
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Protein Binding - drug effects
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Thiazoles - administration & dosage
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Time Factors -
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Alzheimer's disease
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drug delivery
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drug targeting
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dynamic light scattering
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senile plaque