Thioflavins released from nanoparticles target fibrillar amyloid beta in the hippocampus of APP/PS1 transgenic mice.
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.
Siegemund
T
T
Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, D-04109 Leipzig, Germany.
Paulke
B-R
BR
Schmiedel
H
H
Bordag
N
N
Hoffmann
A
A
Harkany
T
T
Tanila
H
H
Kacza
J
J
Härtig
W
W
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D049329:Nanostructures; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage*; D013997:Time Factors
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; D013844:Thiazoles; C009462:thioflavin T