title: Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood-brain barrier.
abstract: Nanoparticle-based platforms have drawn considerable attention for their potential effect on oncology and other biomedical fields. However, their in vivo application is challenged by insufficient accumulation and retention within tumors due to limited specificity to the target, and an inability to traverse biological barriers. Here, we present a nanoprobe that shows an ability to cross the blood-brain barrier and specifically target brain tumors in a genetically engineered mouse model, as established through in vivo magnetic resonance and biophotonic imaging, and histologic and biodistribution analyses. The nanoprobe is comprised of an iron oxide nanoparticle coated with biocompatible polyethylene glycol-grafted chitosan copolymer, to which a tumor-targeting agent, chlorotoxin, and a near-IR fluorophore are conjugated. The nanoprobe shows an innocuous toxicity profile and sustained retention in tumors. With the versatile affinity of the targeting ligand and the flexible conjugation chemistry for alternative diagnostic and therapeutic agents, this nanoparticle platform can be potentially used for the diagnosis and treatment of a variety of tumor types.
authors.affiliation: Departments of Materials Science and Engineering, University of Washington, Seattle, Washington 99195, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Veiseh
authors.forename: Conroy
authors.initials: C
authors.lastname: Sun
authors.forename: Chen
authors.initials: C
authors.lastname: Fang
authors.forename: Narayan
authors.initials: N
authors.lastname: Bhattarai
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gunn
authors.forename: Forrest
authors.initials: F
authors.lastname: Kievit
authors.forename: Kim
authors.initials: K
authors.lastname: Du
authors.forename: Barbara
authors.initials: B
authors.lastname: Pullar
authors.forename: Donghoon
authors.initials: D
authors.lastname: Lee
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
authors.forename: Jim
authors.initials: J
authors.lastname: Olson
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005290:Ferric Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D012604:Scorpion Venoms / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005290:Ferric Compounds; D012604:Scorpion Venoms; C091539:Chlorotoxin; C000499:ferric oxide; D011092:Polyethylene Glycols; D048271:Chitosan