Nanoparticles for Delivery of Imaging Probes Through the Blood-Brain-Barrier In Vivo in Alzheimer’s Disease Model Mice

When: Wednesday, March 14, 2012 at 10:30 am
Where: EG 306
Speaker: Tara L. Spire-Jones, DPhil
Organization: Instructor in Neurology, Harvard Medical School, Assistant in Neuroscience, MGH
Sponsor: IGERT

In vivo imaging of animal models of neurodegenerative disease has proved a valuable tool for studying the dynamics of degenerative processes. However, imaging is hampered by the necessity of introducing contrast agents through the blood brain barrier (BBB). Poly(n-butyl cyanoacrylate) dextran polymers coated with polysorbate-80 (PBCA nanoparticles) are promising agents for circumventing the BBB that we have developed for targeting BBB impermeable imaging agents ranging from 500 Da to 150,000 Da into the brains of anesthetized Alzheimer’s disease transgenic mouse models. Using this technique, we have introduced nuclear markers to follow cells over time, amyloid plaque labeling dyes, and fluorescently labeled antibodies. Mechanistically, we find that PBCA nanoparticles do not induce nonspecific BBB disinteruption (confirmed with EM and MRI), but collaborate with plasma apolipoprotein E to facilitate BBB crossing (demonstrated by lack of efficacy in apolipoprotein E knockout mice). Collectively, these findings highlight the potential of using nanocarrier systems to deliver BBB-impermeable targeted molecular probes into the brain for diagnostic neuroimaging.