title: Enhanced magnetic resonance imaging of experimental pancreatic tumor in vivo by block copolymer-coated magnetite nanoparticles with TGF-beta inhibitor.
abstract: Early detection of solid tumors, particularly pancreatic cancer, is of substantial importance in clinics. Enhanced magnetic resonance imaging (MRI) with iron oxide nanoparticles is an available way to detect the cancer. The effective and selective accumulation of these nanoparticles in the tumor tissue is needed for improved imaging, and in this regard, their longevity in the blood circulation time is crucial. We developed here block copolymer-coated magnetite nanoparticles for pancreatic cancer imaging, by means of a chelation between the carboxylic acid groups in poly(ethylene glycol)-poly(aspartic acid) block copolymer (PEG-PAsp) and Fe on the surface of the iron oxide nanoparticles. These nanoparticles had considerably narrow distribution, even upon increased ionic strength or in the presence of fetal bovine serum. The PEG-PAsp-coated nanoparticles were further shown to be potent as a contrast agent for enhanced MRI for an experimental pancreatic cancer, xenografts of the human-derived BxPC3 cell line in BALB/c nude mice, with combined administration of TGF-beta inhibitor. Iron staining of tumor tissue confirmed the accumulation of the nanoparticles in tumor tissue. Use of the PEG-PAsp-coated magnetite nanoparticles, combined with the TGF-beta inhibitor, is of promising clinical importance for the detection of intractable solid cancers, including pancreatic cancer.
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kumagai
authors.forename: Mitsunobu R
authors.initials: MR
authors.lastname: Kano
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Morishita
authors.forename: Motomi
authors.initials: M
authors.lastname: Ota
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Sekino
authors.forename: Shoogo
authors.initials: S
authors.lastname: Ueno
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazono
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004563:Electrochemistry; D005260:Female; D052203:Ferrosoferric Oxide; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008027:Light; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D012542:Scattering, Radiation; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D007202:Indicators and Reagents; D016212:Transforming Growth Factor beta; C493635:polyethylene glycol-block-polyaspartic acid; D011092:Polyethylene Glycols; D052203:Ferrosoferric Oxide