The purpose of this study was to use a near-infrared (NIR) fluorescent cyclic His-Try-
Gly-Phe peptide to characterize and image the expressions of
matrix metalloproteinases (
MMPs), which are correlated with
cancer promotion, in an
inflammation-induced
colorectal cancer (ICRC) model. We explored the relationship between the development of
colon cancer and the expression of
MMPs at the same colonic sites in ICRC models. To develop ICRC models, mice were administered a single intraperitoneal dose (10 mg/kg) of
azoxymethane (AOM) and exposed orally to 2%
dextran sodium sulfate (DSS) for one week. MMP-2 expression and β-
catenin activation in colonic lesions were characterized by immunohistochemical (IHC) staining. After being treated with inducers for some time, cancerous lesions were found to express high β-
catenin and MMP-2. The profiles of
MMP expression were correlated with β-
catenin activation in the colonic lesions. c(KAHWGFTLD)NH(2) (C6)
peptide was prepared by standard Fmoc
peptide synthesis to target
MMPs. Molecular weight of Cy5.5-C6 was 1,954.78 g/mol (calculated MW = 1955.23 g/mol). The in vitro characterization of Cy5.5-C6 showed
MMP binding specificity in a cell experiment. In vivo NIRF imaging showed high accumulation of Cy5.5-C6 in
tumors with associated expression of MMP-2 in colonic lesions after
intravenous injection. The MMP-2 specificity of Cy5.5-C6 was confirmed by successful inhibition of probe uptake in the
tumor due to the presence of excess C6
peptide. The use of Cy5.5-C6 to target MMP-2 has the potential to be developed into an effective molecular imaging agent to monitor ICRC progress.