title: Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: potential for targeting experimental brain tumors.
abstract: Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50nm or 120nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors.
  
  
  BACKGROUND
  This study demonstrates the use of magnetic resonance image-guided transcranial focused ultrasound to open the BBB and enable spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS)-based molecular imaging for experimental tumor tracking.
authors.affiliation: The Hospital for Sick Children, Arthur & Sonia Labatt Brain Tumour Research Centre, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Roberto Jose
authors.initials: RJ
authors.lastname: Diaz
authors.affiliation: Division of Biophysics and Imaging, Ontario Cancer Institute, University Health Network, and the University of Toronto, Toronto, Canada.
authors.forename: Patrick Z
authors.initials: PZ
authors.lastname: McVeigh
authors.affiliation: Division of Imaging Research at Sunnybrook Research Institute, and Department of Medical Biophysics at the University of Toronto, Toronto, Canada.
authors.forename: Meaghan A
authors.initials: MA
authors.lastname: O'Reilly
authors.affiliation: The Hospital for Sick Children, Arthur & Sonia Labatt Brain Tumour Research Centre, Toronto, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Burrell
authors.affiliation: The Hospital for Sick Children, Arthur & Sonia Labatt Brain Tumour Research Centre, Toronto, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bebenek
authors.affiliation: The Hospital for Sick Children, Arthur & Sonia Labatt Brain Tumour Research Centre, Toronto, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Neuro-Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Etame
authors.affiliation: Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Toronto Western Hospital University Health Network, Toronto, Canada.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Zadeh
authors.affiliation: Division of Imaging Research at Sunnybrook Research Institute, and Department of Medical Biophysics at the University of Toronto, Toronto, Canada.
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
authors.affiliation: Division of Biophysics and Imaging, Ontario Cancer Institute, University Health Network, and the University of Toronto, Toronto, Canada.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.affiliation: The Hospital for Sick Children, Arthur & Sonia Labatt Brain Tumour Research Centre, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada. Electronic address: james.rutka@sickkids.ca.
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000528:radiation effects*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism*; D051381:Rats; D013016:Sound
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors
keywords: Blood-brain barrier; Focused ultrasound; Giloma; Imaging; Nanoparticles