Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood-brain barrier.
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.
Veiseh
Omid
O
Departments of Materials Science and Engineering, University of Washington, Seattle, Washington 99195, USA.
Sun
Conroy
C
Fang
Chen
C
Bhattarai
Narayan
N
Gunn
Jonathan
J
Kievit
Forrest
F
Du
Kim
K
Pullar
Barbara
B
Lee
Donghoon
D
Ellenbogen
Richard G
RG
Olson
Jim
J
Zhang
Miqin
M
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
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005290:Ferric Compounds; D012604:Scorpion Venoms; C091539:Chlorotoxin; C000499:ferric oxide; D011092:Polyethylene Glycols; D048271:Chitosan