title: Multi-modal detection of colon malignancy by NIR-tagged recognition polymers and ultrasound contrast agents.
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.
authors.affiliation: The Hebrew University of Jerusalem, Faculty of Medicine, The School of Pharmacy Institute for Drug Research, P.O. Box 12065, Jerusalem 91120, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Bloch
authors.affiliation: Drexel University, School of Biomedical Engineering, Science & Health Systems, Philadelphia 19104, PA, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Jablonowski
authors.affiliation: The Hebrew University of Jerusalem, Faculty of Medicine, The School of Pharmacy Institute for Drug Research, P.O. Box 12065, Jerusalem 91120, Israel.
authors.forename: Eylon
authors.initials: E
authors.lastname: Yavin
authors.affiliation: The Hebrew University of Jerusalem, Faculty of Medicine, The School of Pharmacy Institute for Drug Research, P.O. Box 12065, Jerusalem 91120, Israel.
authors.forename: Dorit
authors.initials: D
authors.lastname: Moradov
authors.affiliation: The Hebrew University of Jerusalem, Faculty of Medicine, The School of Pharmacy Institute for Drug Research, P.O. Box 12065, Jerusalem 91120, Israel.
authors.forename: Irena
authors.initials: I
authors.lastname: Djavsarov
authors.affiliation: Timrat 36576, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.affiliation: Drexel University, School of Biomedical Engineering, Science & Health Systems, Philadelphia 19104, PA, USA. Electronic address: wheatley@coe.drexel.edu.
authors.forename: Margaret
authors.initials: M
authors.lastname: Wheatley
authors.affiliation: The Hebrew University of Jerusalem, Faculty of Medicine, The School of Pharmacy Institute for Drug Research, P.O. Box 12065, Jerusalem 91120, Israel. Electronic address: avrir@ekmd.huji.ac.il.
authors.forename: Abraham
authors.initials: A
authors.lastname: Rubinstein
mesh_terms: D000162:Acoustics; D000180:Acrylic Resins / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D045423:Microbubbles; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D014463:Ultrasonography; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D003287:Contrast Media; D005456:Fluorescent Dyes; D019344:Lactic Acid; D010446:Peptide Fragments; D011091:Polyesters; D011108:Polymers; D000099166:Polyacrylamides; C033616:poly(lactide)
keywords: Cationized polyacrylamide; Colon cancer; Microbubbles; Real time diagnosis; Recognition peptide; Ultrasound