The relative roles of charge and a recognition peptide in luminal targeting of colorectal cancer by fluorescent polyacrylamide

Meital Bloch, Yossi Kam, Eylon Yavin, Dorit Moradov, Aviram Nissan, Ilana Ariel, Abraham Rubinstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Real time detection of biomarkers at the mucosal level is imperative for the prevention and efficient treatment of colorectal cancer. Cationized polyacrylamide (CPAA) with increasing charge densities was prepared by radical polymerization of acrylamide and different mol% ratios of N-acryloyl, N′-(tert-butyl-carbonyl) diaminoethane. The NIR fluorophore derivative of IR-783, IR-783-S-Ph-COOH, was attached to the CPAA to give CPAA-783. After selecting the optimal IR-783-S-Ph-COOH ratio that avoids quenching, the preferential binding of the polymer was tested in SW-620, SW-480, HT-29, and LS-174T cancer cells. The optimal polymeric product was tested in situ in gut sac preparations of the dimethylhydrazine induced rat model. To increase the detection capabilities of CPAA-783, the FITC-labeled peptide EPPT1, that targets the cell transmembrane underglycosylated MUC-1 (uMUC-1), was conjugated to the polymer to obtain CPAA-783-EPPT1. The dually labeled modified polymer was tested in HT-29 and LS-174T cells (over expressing uMUC-1), followed by an examination in an orthotopic mouse model. CPAA-783 preferentially bound to the cancer cells, depending on CRC staging. The best binding occurred when the fraction of the cationic monomer was 100 mol%, labeled with 0.75 mol% of IR-783-S-Ph-COOH. An increase in the recognition of the dually labeled polymeric product, CPAA-783-EPPT1, towards HT-29 and LS-174T cells occurred in the lowest EPPT1 molar ratio (0.63 mol%) only, probably due to quenching phenomena and steric hindrance. Similar observation was obtained in the orthotopic mice. It is concluded that fluorescently tagged CPAA can be used for the detection of malignant tissues in colorectal cancer after luminal instillation. Dually targeted CPAA with EPPT1is feasible, but requires further optimization.

Original languageAmerican English
Pages (from-to)904-913
Number of pages10
JournalEuropean Journal of Pharmaceutical Sciences
Issue number5
StatePublished - 18 Dec 2012

Bibliographical note

Funding Information:
The results reported here are included in the dissertation project of Y.K. in partial fulfillment of his Ph.D. degree and MB in partial fulfillment of her M.Sc. degree requirements at The Hebrew University of Jerusalem. The work was supported by a research grant # 38813 from the Biomedical Photonics Consortium of the Israeli Ministry of Industry and Trade. The skilful assistance of Ms. R. Carmeli from the Authority of Biological and Biomedical Models in the conductance of the rat studies and Ms. M. Steiner, Harlan Laboratories, Israel, in the conductance of the murine studies is greatly appreciated.


  • Cationized polyacrylamide
  • Colon cancer
  • EEPT-1 peptide
  • In vivo recognition
  • Near-IR imaging
  • Real time diagnosis


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