Bispecific antibody conjugated manganese-based magnetic engineered iron oxide for imaging of HER2/neu- and EGFR-expressing tumors

Shou Cheng Wu, Yu Jen Chen, Hsiang Ching Wang, Min Yuan Chou, Teng Yuan Chang, Shyng Shiou Yuan, Chiao Yun Chen, Ming Feng Hou, John Tsu An Hsu, Yun-Ming Wang*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The overexpression of HER2/neu and EGFR receptors plays important roles in tumorigenesis and tumor progression. Targeting these two receptors simultaneously can have a more widespread application in early diagnosis of cancers. In this study, a new multifunctional nanoparticles (MnMEIO-CyTE777-(Bis)-mPEG NPs) comprising a manganese-doped iron oxide nanoparticle core (MnMEIO), a silane-amino functionalized poly(ethylene glycol) copolymer shell, a near infrared fluorescence dye (CyTE777), and a covalently conjugated anti-HER2/neu and anti-EGFR receptors bispecific antibody (Bis) were successfully developed. In vitro T 2 -weighted MR imaging studies in SKBR-3 and A431 tumor cells incubated with MnMEIO-CyTE777-(Bis)-mPEG NPs showed - 94.8 ± 3.8 and - 84.1 ± 2.8% negative contrast enhancement, respectively. Pharmacokinetics study showed that MnMEIO-CyTE777-(Bis)-mPEG NPs were eliminated from serum with the half-life of 21.3 mins. In vivo MR imaging showed that MnMEIO-CyTE777-(Bis)-mPEG NPs could specifically and effectively target to HER2/neu- and EGFR-expressing tumors in mice; the relative contrast enhancements were 11.8 (at 2 hrs post-injection) and 61.5 (at 24 hrs post-injection) fold higher in SKBR-3 tumors as compared to Colo-205 tumors. T 2 -weighted MR and optical imaging studies revealed that the new contrast agent (MnMEIO-CyTE777-(Bis)-mPEG NPs) could specifically and effectively target to HER2/neu- and/or EGFR-expressing tumors. Our results demonstrate that MnMEIO-CyTE777-(Bis)-mPEG NPs are able to recognize the tumors expressing both HER2/neu and/or EGFR, and may provide a novel molecular imaging tool for early diagnosis of cancers expressing HER2/neu and/or EGFR.

Original languageEnglish
Pages (from-to)118-130
Number of pages13
JournalTheranostics
Volume6
Issue number1
DOIs
StatePublished - 1 Jan 2016

Keywords

  • Bispecific antibody
  • EGFR
  • HER2/neu
  • Magnetic resonance imaging
  • MnMEIO

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    Wu, S. C., Chen, Y. J., Wang, H. C., Chou, M. Y., Chang, T. Y., Yuan, S. S., Chen, C. Y., Hou, M. F., Hsu, J. T. A., & Wang, Y-M. (2016). Bispecific antibody conjugated manganese-based magnetic engineered iron oxide for imaging of HER2/neu- and EGFR-expressing tumors. Theranostics, 6(1), 118-130. https://doi.org/10.7150/thno.13069