New Nanoengineered Neuroprobes for Magnetic Resonance Imaging of Dopamine Transporters

When: Friday, November 22, 2013 at 1:00 pm
Where: SNL 121
Speaker: Gordana Vitaliano, MD, MS
Organization: Director, Brain Imaging Nanotechnology Group (BING), McLean Hospital, Harvard Medical School
Sponsor: IGERT Nanomedicine Seminar

Magnetic Resonance Imaging (MRI) is a noninvasive visualization technique with high spatial resolution, but low sensitivity for visualization of brain transporters or receptors. Gadolinium (Gd) contrast agents are used to improve MRI sensitivity, but they cannot cross an intact blood-brain-barrier (BBB). Our goal was to develop MRI Gd-nanoprobes with high T1 relaxivity that can cross an intact BBB and target dopamine transporters (DAT) in the rat brain. We found that clathrin nanoparticles can be constituted as triskelia (18.5 nm in size) and assembled in cages (55 nm) with high relaxivity. These clathrin triskelia and cages can serve as robust MRI nanoplatforms onto which multiple functional motifs can be added through chemical modifications. Clathrin cages exhibited 20 times higher ionic relaxivity and 8,000-fold greater molecular relaxivity than gadopentetate dimeglumine. Clathrin-nanoplatforms successfully crossed and/or bypassed an intact BBB without enhancers. Triskelia were also able to deliver adequate concentrations of Gdcontrast agent and DAT-ligands to the rat brain and to target dopamine transporters. These results should encourage further investigations into the use of clathrin as a new brain imaging and drug delivery nanoplatform. This technology may lead to development of non-radioactive, stable molecular nanoprobes to assist in early detection of neurobiological changes in dopamine-related disorders (e.g., Parkinson’s, Huntington’s Disease, ADHD, drug addiction, psychotic disorders etc.); to monitor progression of the disease and recovery process; and to help evaluate the effectiveness of drugs aimed at treating these disorders.