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Fabrication of polymer-gadolinium (III) complex nanomicelle from poly(ethylene glycol)-polysuccinimide conjugate and diethylenetriaminetetraacetic acid-gadolinium as magnetic resonance imaging contrast agents

Authors

  • Wei-Lu Zhang,

    1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
    2. Department of Applied Chemistry, College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325035, Zhejiang Province, People's Republic of China
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  • Da-Wei Yong,

    1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
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  • Jin Huang,

    1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
    2. College of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, People's Republic of China
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  • Jia-Hui Yu,

    Corresponding author
    1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
    • Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
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  • Shi-Yuan Liu,

    Corresponding author
    1. Department of Diagnostic Imaging, Changzheng Hospital, Shanghai 200003, People's Republic of China
    • Department of Diagnostic Imaging, Changzheng Hospital, Shanghai 200003, People's Republic of China
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  • Ming-Xia Fan

    1. Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai 200062, People's Republic of China
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Abstract

Methoxy poly (ethylene glycol)-graft-α, β-poly (aspartic acid) derivatives (mPEG-g-PAA-N3) were synthesized by sequential ring-opening reaction of polysuccinimide (PSI) with mPEG-NH2 (MW: 2000 Da), and 1-azido-3-aminopropane, respectively. Then N2-(hex-5-yne)-diethylenetriamine-tetra-t-butylacetate (DTTA-der) was conjugated to mPEG-g-PAA-N3 by click cycloaddition. After deprotection of carboxylic groups, mPEG-g-PAA-DTTA macromolecular ligands were obtained. MPEG-g-PAA-(DTTA-Gd) complex nanomicelles were fabricated from mPEG-g-PAA-DTTA and Gadolinium chloride. The formation of nanomicelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. It was found that all the nanomicelles showed spherical shapes with core-shell structures and narrow size distributions. Their sizes ranged from 50 to 80 nm, suggesting their passive targeting potential to tumor tissue. With the increase of graft degree (GD) of mPEG, the sizes of mPEG-g-PAA-(DTTA-Gd) nanomicelles showed a tendency to decrease. Compared with gadopentetate dimeglumine (Gd-DTPA), mPEG-g-PAA-(DTTA-Gd) nanomicelles showed essential decreased cytotoxicity to KB cell line and enhanced T1-weighted signal intensity, especially at low concentration of gadolinium (III), suggesting their great potentials as magnetic resonance imaging contrast agents. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

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