title: Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors.
abstract: This study explored the possibility of utilizing iron oxide nanoparticles as a drug delivery vehicle for minimally invasive, MRI-monitored magnetic targeting of brain tumors. In vitro determined hydrodynamic diameter of approximately 100 nm, saturation magnetization of 94 emicro/g Fe and T2 relaxivity of 43 s(-1)mm(-)(1) of the nanoparticles suggested their applicability for this purpose. In vivo effect of magnetic targeting on the extent and selectivity of nanoparticle accumulation in tumors of rats harboring orthotopic 9L-gliosarcomas was quantified with MRI. Animals were intravenously injected with nanoparticles (12 mg Fe/kg) under a magnetic field density of 0 T (control) or 0.4 T (experimental) applied for 30 min. MR images were acquired prior to administration of nanoparticles and immediately after magnetic targeting at 1h intervals for 4h. Image analysis revealed that magnetic targeting induced a 5-fold increase in the total glioma exposure to magnetic nanoparticles over non-targeted tumors (p=0.005) and a 3.6-fold enhancement in the target selectivity index of nanoparticle accumulation in glioma over the normal brain (p=0.025). In conclusion, accumulation of iron oxide nanoparticles in gliosarcomas can be significantly enhanced by magnetic targeting and successfully quantified by MR imaging. Hence, these nanoparticles appear to be a promising vehicle for glioma-targeted drug delivery.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Chertok
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Moffat
authors.forename: Allan E
authors.initials: AE
authors.lastname: David
authors.forename: Faquan
authors.initials: F
authors.lastname: Yu
authors.forename: Christian
authors.initials: C
authors.lastname: Bergemann
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009368:Neoplasm Transplantation; D051381:Rats
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; C000499:ferric oxide