標題: Peptide-based MRI contrast agent and near-infrared fluorescent probe for intratumoral legumain detection
作者: Chen, Yu-Jen
Wu, Shou-Cheng
Chen, Chung-Yung
Tzou, Shey-Cherng
Cheng, Tian-Lu
Huang, Ying-Fang
Yuan, Shyng-Shiou
Wang, Yun-Ming
生物科技學系
Department of Biological Science and Technology
關鍵字: Legumain;MRI;Optical imaging;Contrast agent
公開日期: 1-一月-2014
摘要: Recent studies suggest that intratumoral legumain promotes tumorigenesis. To monitor legumain activity in tumors, we developed a new MM contrast agent ([Gd-NBCB-TTDA-Leg(L)]) and a NIR fluorescence probe (CyTE777-Leg(L)-CyTE807). The MRI contrast agent was prepared by introduction of cyclobutyl and benzyl group residues to TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triaza-dodecanedioic acid), followed by the attachment of a legumain-specific substrate peptide (Leg(L)). The NIR fluorescence probe was designed by conjugating two NIR fluorochromes (CyTE777 and CyTE807) with Leg(L). Peptide cleavage of the MM contrast agent by legumain can increase its hydrophobicity and promote rotational correlation time (tau(R)). Peptide cleavage of the NIR probes by the legumain relieves the self quench of the probe. Peptide cleavage of the MRI contrast agent and the NIR fluorescence probe by legumain were confirmed by T-1 relaxometric studies and by fluorescence studies, respectively. In vivo MR images showed that [Gd-NBCB-TTDA-Leg(L)] attained 55.3 fold (254.2% versus 4.6%, at 2.0 h post-injection) higher imaging enhancement, as compared with control contrast agent bearing a noncleaveable peptide ([Gd-NBCB-TTDA-Leg(D)], in the CT-26 (legumain(+)) tumors. Similarly, optical imaging probe CyTE777-Leg(L)-CyTE807 attained 15.2 fold (3.34 x 10(9) photons/min versus 0.22 x 10(9) photons/min, at 24.0 h post-injection) higher imaging enhancement in the CT-26 (legumain(+)) tumors, compared to a NIR control probe (CyTE777-Leg(D)-CyTE807). These data indicate that the [Gd-NBCB-TTDA-Leg(L)] and the CyTE777-Leg(L)-CyTE807 probes may be promising tools to image the legumain-expressing cancers for diagnoses and targeted treatments. (C) 2013 Elsevier Ltd. All rights reserved.
URI: http://dx.doi.org/10.1016/j.biomaterials.2013.09.100
http://hdl.handle.net/11536/23194
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2013.09.100
期刊: BIOMATERIALS
Volume: 35
Issue: 1
起始頁: 304
結束頁: 315
顯示於類別:期刊論文


文件中的檔案:

  1. 000328006100030.pdf