Get access

Gadolinium-conjugated folate–poly(ethylene glycol)–polyamidoamine dendrimer–carboxyl nanoparticles as potential tumor-targeted, circulation-prolonged macromolecular magnetic resonance imaging contrast agents. II

Authors

  • Wei-Lu Zhang,

    Corresponding author
    1. Department of Applied Chemistry, College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, Zhejiang Province, People's Republic of China
    2. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
    • Wei-Lu Zhang, Department of Applied Chemistry, College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, Zhejiang Province, People's Republic of China===

      Jia-Hui Yu, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China===

    Search for more papers by this author
  • Na Li,

    1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
    Search for more papers by this author
  • Jin Huang,

    1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
    Search for more papers by this author
  • Shu-Fang Luo,

    1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
    Search for more papers by this author
  • Ming-Xia Fan,

    1. Shanghai Key Laboratory of Functional Magnetic Resonance Imaging, East China Normal University, Shanghai 200062, People's Republic of China
    Search for more papers by this author
  • Shi-Yuan Liu,

    1. Department of Diagnostic Imaging, Changzheng Hospital, Shanghai 200003, People's Republic of China
    Search for more papers by this author
  • Ben Muir,

    1. The Commonwealth Scientific and Industrial Research Organisation, Bayview Ave, Bag 10, Clayton South, Melbourne, Victoria 3169, Australia
    Search for more papers by this author
  • Jia-Hui Yu

    Corresponding author
    1. Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China
    • Wei-Lu Zhang, Department of Applied Chemistry, College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, Zhejiang Province, People's Republic of China===

      Jia-Hui Yu, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, People's Republic of China===

    Search for more papers by this author

Abstract

A new macromolecular gadolinium-based magnetic resonance imaging (MRI) contrast agent, folic acid (FA)–poly(ethylene glycol) (PEG)–polyamidoamine dendrimer (PAMAM)–Gd, was synthesized with a core of PAMAM, which was modified with conjugates of FA and PEG and then chelated by gadolinium ions. The final products, with FA as the targeting moiety, were evaluated for their tumor-targeting MRI contrast-agent potential. The concentration detection limits in vitro; contrast-enhanced MRI in the heart, kidney, and liver of mice; and metabolism of FA–PEG–PAMAM–Gd were measured by a Siemens Tim Trio human MRI scanner at 3 T. Transmission electron microscopy was used to determine the targeting of FA–PEG–PAMAM–Gd to human epidermoid carcinomas cell lines (KB) or murine aneuploid fibrosarcoma cell lines (L929). The toxicity was also assayed to evaluate the biocompatibility of this contrast agent. The minimum detectable concentration of FA–PEG4K–PAMAM–Gd (where the subscript 4K indicates a molecular weight of 4000 Da) was 15-fold lower than that of the commercially available contrast agent gadopentetate dimeglumine. The MRI images displayed a gradual persistent signal enhancement on tumors, and millimeter-sized (∼ 3 mm) tumors were well visualized with FA–PEG4K–PAMAM–Gd. In conclusion, the dendritic complexes were well suited for use as an FA-mediated targeting contrast agent for early diagnosis of tumors in mice. The dendritic contrast agents displayed lower concentration detection limits, which suggests their future use in molecular imaging. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Ancillary