TY - JOUR
T1 - Enhanced magnetic resonance imaging of experimental pancreatic tumor in vivo by block copolymer-coated magnetite nanoparticles with TGF-β inhibitor
AU - Kumagai, Michiaki
AU - Kano, Mitsunobu R.
AU - Morishita, Yasuyuki
AU - Ota, Motomi
AU - Imai, Yutaka
AU - Nishiyama, Nobuhiro
AU - Sekino, Masaki
AU - Ueno, Shoogo
AU - Miyazono, Kohei
AU - Kataoka, Kazunori
N1 - Funding Information:
The authors thank Dr James R. Christie II, The University of Tokyo, for editing the English of the manuscript. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Core Research for Evolution of Science and Technology (CREST), Japan Science and Technology Corporation (JST), and the 21st century COE program ‘Human-Friendly Materials based on Chemistry’ from MEXT.
PY - 2009/12/16
Y1 - 2009/12/16
N2 - 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-β 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-β inhibitor, is of promising clinical importance for the detection of intractable solid cancers, including pancreatic cancer. Graphical abstract: {A figure is presented}.
AB - 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-β 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-β inhibitor, is of promising clinical importance for the detection of intractable solid cancers, including pancreatic cancer. Graphical abstract: {A figure is presented}.
KW - Magnetic resonance imaging
KW - Magnetite nanoparticles
KW - Pancreatic cancer
KW - Poly(ethylene glycol)
KW - TGF-β
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U2 - 10.1016/j.jconrel.2009.06.002
DO - 10.1016/j.jconrel.2009.06.002
M3 - Article
C2 - 19524625
AN - SCOPUS:70449719188
SN - 0168-3659
VL - 140
SP - 306
EP - 311
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -