title: Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice.
abstract: OBJECTIVE
  To study the distribution and clearance of polyethylene glycol (PEG)-ylated single-walled carbon nanotube (SWCNTs) as drug delivery vehicles for the anticancer drug cisplatin in mice.
  
  
  METHODS
  PEG layers were attached to SWCNTs and dispersed in aqueous media and characterized using dynamic light scattering, scanning transmission electron microscopy and Raman spectroscopy. Cytotoxicity was assessed in vitro using Annexin-V assay, and the distribution and clearance pathways in mice were studied by histological staining and Raman spectroscopy. Efficacy of PEG-SWCNT-cisplatin for tumor growth inhibition was studied in mice.
  
  
  CONCLUSIONS
  PEG-SWCNTs were efficiently dispersed in aqueous media compared with controls, and did not induce apoptosis in vitro. Hematoxylin and eosin staining, and Raman bands for SWCNTs in tissues from several vital organs from mice injected intravenously with nanotube bioconjugates revealed that control SWCNTs were lodged in lung tissue as large aggregates compared with the PEG-SWCNTs, which showed little or no accumulation. Characteristic SWCNT Raman bands in feces revealed the presence of bilary or renal excretion routes. Attachment of cisplatin on bioconjugates was visualized with Z-contrast scanning transmission electron microscopy. PEG-SWCNT-cisplatin with the attached targeting ligand EGF successfully inhibited growth of head and neck tumor xenografts in mice.
  
  
  CONCLUSIONS
  PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors.
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs, CT, USA.
authors.forename: Ashwin A
authors.initials: AA
authors.lastname: Bhirde
authors.forename: Sachin
authors.initials: S
authors.lastname: Patel
authors.forename: Alioscka A
authors.initials: AA
authors.lastname: Sousa
authors.forename: Vyomesh
authors.initials: V
authors.lastname: Patel
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Molinolo
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Ji
authors.forename: Richard D
authors.initials: RD
authors.lastname: Leapman
authors.forename: J Silvio
authors.initials: JS
authors.lastname: Gutkind
authors.forename: James F
authors.initials: JF
authors.lastname: Rusling
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006258:Head and Neck Neoplasms / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017348:Microscopy, Electron, Scanning Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry*; D013059:Spectrum Analysis, Raman
chemical_list: D037742:Nanotubes, Carbon; D011092:Polyethylene Glycols