title: Enhanced delivery of gold nanoparticles with therapeutic potential into the brain using MRI-guided focused ultrasound.
abstract: The blood brain barrier (BBB) is a major impediment to the delivery of therapeutics into the central nervous system (CNS). Gold nanoparticles (AuNPs) have been successfully employed in multiple potential therapeutic and diagnostic applications outside the CNS. However, AuNPs have very limited biodistribution within the CNS following intravenous administration. Magnetic resonance imaging guided focused ultrasound (MRgFUS) is a novel technique that can transiently increase BBB permeability allowing delivery of therapeutics into the CNS. MRgFUS has not been previously employed for delivery of AuNPs into the CNS. This work represents the first demonstration of focal enhanced delivery of AuNPs into the CNS using MRgFUS in a rat model both safely and effectively. Histologic visualization and analytical quantification of AuNPs within the brain parenchyma suggest BBB transgression. These results suggest a role for MRgFUS in the delivery of AuNPs with therapeutic potential into the CNS for targeting neurological diseases.
  
  
  BACKGROUND
  Gold nanoparticles have been successfully utilized in experimental diagnostic and therapeutic applications; however, the blood-brain barrier (BBB) is not permeable to these particles. In this paper, the authors demonstrated that MRI guided focused ultrasound is capable to transiently open the BBB thereby enabling CNS access.
authors.affiliation: The Hospital for Sick Children - Arthur and Sonia Labatt Brain Tumour Research Centre, Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada.
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Etame
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Diaz
authors.forename: Meaghan A
authors.initials: MA
authors.lastname: O'Reilly
authors.forename: Christian A
authors.initials: CA
authors.lastname: Smith
authors.forename: Todd G
authors.initials: TG
authors.lastname: Mainprize
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000528:radiation effects; D001921:Brain / Q000378:metabolism* / Q000528:radiation effects; D016503:Drug Delivery Systems / Q000379:methods*; D006046:Gold / Q000737:chemistry / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D013016:Sound
chemical_list: D006046:Gold