Peptide-based MRI contrast agent and near-infrared fluorescent probe for intratumoral legumain detection

Yu Jen Chen, Shou Cheng Wu, Chung Yung Chen, Shey-Cherng Tzou, Tian Lu Cheng, Ying Fang Huang, Shyng Shiou Yuan, Yun-Ming Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Recent studies suggest that intratumoral legumain promotes tumorigenesis. To monitor legumain activity in tumors, we developed a new MRI 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 MRI contrast agent by legumain can increase its hydrophobicity and promote rotational correlation time (τR). 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 T1 relaxometric studies and by fluorescence studies, respectively. Invivo MR images showed that [Gd-NBCB-TTDA-Leg(L)] attained 55.3 fold (254.2% versus 4.6%, at 2.0h 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 (3.34×109 photons/min versus 0.22×109 photons/min, at 24.0h 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.

Original languageEnglish
Pages (from-to)304-315
Number of pages12
JournalBiomaterials
Volume35
Issue number1
DOIs
StatePublished - 1 Jan 2014

Keywords

  • Contrast agent
  • Legumain
  • MRI
  • Optical imaging

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