Thioflavins released from nanoparticles target fibrillar amyloid beta in the hippocampus of APP/PS1 transgenic mice

Int J Dev Neurosci. 2006 Apr-May;24(2-3):195-201. doi: 10.1016/j.ijdevneu.2005.11.012. Epub 2005 Dec 28.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Benzothiazoles
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Mice
  • Mice, Transgenic
  • Nanostructures
  • Neurofibrillary Tangles / drug effects*
  • Neurofibrillary Tangles / metabolism
  • Protein Binding / drug effects
  • Thiazoles / administration & dosage*
  • Time Factors

Substances

  • Amyloid
  • Amyloid beta-Protein Precursor
  • Benzothiazoles
  • Thiazoles
  • thioflavin T