title: Vascular-targeted photothermal therapy of an orthotopic murine glioma model.
abstract: OBJECTIVE
  To develop nanoshells for vascular-targeted photothermal therapy of glioma.
  
  
  METHODS
  The ability of nanoshells conjugated to VEGF and/or poly(ethylene glycol) (PEG) to thermally ablate VEGF receptor-2-positive endothelial cells upon near-infrared laser irradiation was evaluated in vitro. Subsequent in vivo studies evaluated therapy in mice bearing intracerebral glioma tumors by exposing tumors to near-infrared light after systemically delivering saline, PEG-coated nanoshells, or VEGF-coated nanoshells. The treatment effect was monitored with intravital microscopy and histology.
  
  
  RESULTS
  VEGF-coated but not PEG-coated nanoshells bound VEGF receptor-2-positive cells in vitro to enable targeted photothermal ablation. In vivo, VEGF targeting doubled the proportion of nanoshells bound to tumor vessels and vasculature was disrupted following laser exposure. Vessels were not disrupted in mice that received saline. The normal brain was unharmed in all treatment and control mice.
  
  
  CONCLUSIONS
  Nanoshell therapy can induce vascular disruption in glioma.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Day
authors.forename: Linna
authors.initials: L
authors.lastname: Zhang
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Thompson
authors.forename: Janice A
authors.initials: JA
authors.lastname: Zawaski
authors.forename: Caterina C
authors.initials: CC
authors.lastname: Kaffes
authors.forename: M Waleed
authors.initials: MW
authors.lastname: Gaber
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D005910:Glioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D051379:Mice; D057145:Nanoshells / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D010789:Phototherapy / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; D040301:Vascular Endothelial Growth Factor Receptor-2