期刊
ADVANCED MATERIALS
卷 30, 期 33, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201803163
关键词
contrast agents; dotted core-shell nanoparticles; longitudinal relaxivity (r(1)); magnetic resonance imaging; transverse relaxivity (r(2))
类别
资金
- Youth Innovation Promotion Association of the Chinese Academy of Sciences [2016269]
- National Natural Science Foundation of China [51761145021, U1501501, U1432114]
- Public Welfare Technology Application Research Project of Zhejiang Province [2017C33129]
- National Key Research and Development Program [2016YFC1400600, SQ2018YFD080066]
- Intramural Research Program (IRP)
- National Institute of Biomedical Imaging and Bioengineering (NIBIB)
- National Institutes of Health (NIH) [ZIA EB000073]
- Hundred Talents Program of Chinese Academy of Sciences [2010-735]
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [ZIAEB000083, ZIAEB000073] Funding Source: NIH RePORTER
Gd-based T-1-weighted contrast agents have dominated the magnetic resonance imaging (MRI) contrast agent market for decades. Nevertheless, they are reported to be nephrotoxic and the U.S. Food and Drug Administration has issued a general warning concerning their use. In order to reduce the risk of nephrotoxicity, the MRI performance of the Gd-based T-1-weighted contrast agents needs to be improved to allow a much lower dosage. In this study, novel dotted core-shell nanoparticles (FeGd-HN3-RGD2) with superhigh r(1) value (70.0 mM(-1) s(-1)) and very low r(2)/r(1) ratio (1.98) are developed for high-contrast T-1-weighted MRI of tumors. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and histological analyses show good biocompatibility of FeGd-HN3-RGD2. Laser scanning confocal microscopy images and flow cytometry demonstrate active targeting to integrin alpha(v)beta(3) positive tumors. MRI of tumors shows high tumor Delta SNR for FeGd-HN3-RGD2 (477 +/- 44%), which is about 6-7-fold higher than that of Magnevist (75 +/- 11%). MRI and inductively coupled plasma results further confirm that the accumulation of FeGd-HN3-RGD2 in tumors is higher than liver and spleen due to the RGD2 targeting and small hydrodynamic particle size (8.5 nm), and FeGd-HN3-RGD2 is readily cleared from the body by renal excretion.
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