Multi-modal detection of colon malignancy by NIR-tagged recognition polymers and ultrasound contrast agents

Meital Bloch, Lauren Jablonowski, Eylon Yavin, Dorit Moradov, Irena Djavsarov, Abraham Nyska, Margaret Wheatley*, Abraham Rubinstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

To increase colonoscopy capability to discriminate benign from malignant polyps, we suggest combining two imaging approaches based on targeted polymeric platforms. Water-soluble cationized polyacrylamide (CPAA) was tagged with the near infrared (NIR) dye IR-783-S-Ph-COOH to form Flu-CPAA. The recognition peptide VRPMPLQ (reported to bind specifically to CRC tissues) was then conjugated with the Flu-CPAA to form Flu-CPAA-Pep which was then incorporated into echogenic microbubbles (MBs) made of polylactic acid (PLA) that are highly responsive to ultrasound. The ultimate design includes intravenous administration combined with local ultrasound and intra-colon inspection at the NIR range. In this proof of principle study PLA MBs were prepared by the double emulsion technique and loaded with several types of Flu-CPAA-Pep polymers. After insonation the submicron PLA fragments (SPF)-containing Flu-CPAA-Pep were examined in vitro for their ability to attach to colon cancer cells and in vivo (DMH induced rat model) for their ability to attach to colon malignant tissues and compared to the specific attachment of the free Flu-CPAA-Pep. The generation of SPF-containing Flu-CPAA-Pep resulted in a tissue attachment similar to that of the free, unloaded Flu-CPAA-Pep. The addition of VRPMPLQ to the polymeric backbone of the Flu-CPAA reduced cytotoxicity and improved the specific binding.

Original languageAmerican English
Pages (from-to)504-516
Number of pages13
JournalInternational Journal of Pharmaceutics
Volume478
Issue number2
DOIs
StatePublished - 30 Jan 2015

Bibliographical note

Publisher Copyright:
© 2014, Elsevier B.V. All rights reserved.

Keywords

  • Cationized polyacrylamide
  • Colon cancer
  • Microbubbles
  • Real time diagnosis
  • Recognition peptide
  • Ultrasound

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