title: Glioma selectivity of magnetically targeted nanoparticles: a role of abnormal tumor hydrodynamics.
abstract: Magnetic targeting is a promising strategy for achieving localized drug delivery. Application of this strategy to treat brain tumors, however, is complicated by their deep intracranial location, since magnetic field density cannot be focused at a distance from an externally applied magnet. This study intended to examine whether, with magnetic targeting, pathological alteration in brain tumor flow dynamics could be of value in discriminating the diseased site from healthy brain. To address this question, the capture of magnetic nanoparticles was first assessed in vitro using a simple flow system under theoretically estimated glioma and normal brain flow conditions. Secondly, accumulation of nanoparticles via magnetic targeting was evaluated in vivo using 9L-glioma bearing rats. In vitro results that predicted a 7.6-fold increase in nanoparticle capture at glioma- versus contralateral brain-relevant flow rates were relatively consistent with the 9.6-fold glioma selectivity of nanoparticle accumulation over the contralateral brain observed in vivo. Based on these finding, the in vitro ratio of nanoparticle capture can be viewed as a plausible indicator of in vivo glioma selectivity. Overall, it can be concluded that the decreased blood flow rate in glioma, reflecting tumor vascular abnormalities, is an important contributor to glioma-selective nanoparticle accumulation with magnetic targeting.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Chertok
authors.forename: Allan E
authors.initials: AE
authors.lastname: David
authors.forename: Yongzhuo
authors.initials: Y
authors.lastname: Huang
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D002196:Capillaries / Q000502:physiology; D045744:Cell Line, Tumor; D002560:Cerebrovascular Circulation / Q000502:physiology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy; D005910:Glioma / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D004337:Drug Carriers