標題: Bispecific Antibody Conjugated Manganese-Based Magnetic Engineered Iron Oxide for Imaging of HER2/neu- and EGFR-Expressing Tumors
作者: Wu, Shou-Cheng
Chen, Jen
Wang, Hsiang-Ching
Chou, Min-Yuan
Chang, Teng-Yuan
Yuan, Shyng-Shiou
Chen, Chiao-Yun
Hou, Ming-Feng
Hsu, John Tsu-An
Wang, Yun-Ming
生物資訊及系統生物研究所
Institude of Bioinformatics and Systems Biology
關鍵字: bispecific antibody;MnMEIO;magnetic resonance imaging;HER2/neu;EGFR
公開日期: 1-Jan-2016
摘要: 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. T2-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.
URI: http://dx.doi.org/10.7150/thno.13069
http://hdl.handle.net/11536/133583
ISSN: 1838-7640
DOI: 10.7150/thno.13069
期刊: THERANOSTICS
Volume: 6
Issue: 1
起始頁: 118
結束頁: 130
Appears in Collections:Articles


Files in This Item:

  1. 5fa30bed61d796e73588f4f2df8d2ab3.pdf