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

doi:10.1016/j.ijpharm.2014.11.066

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

School of Pharmacy

Research output: Contribution to journal › Article › peer-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 language	American English
Pages (from-to)	504-516
Number of pages	13
Journal	International Journal of Pharmaceutics
Volume	478
Issue number	2
DOIs	https://doi.org/10.1016/j.ijpharm.2014.11.066
State	Published - 30 Jan 2015

Bibliographical note

Funding Information:
The work was supported by a joint research grant from Drexel and HU-IDR and by a research grant from the Alex Grass foundation for Medicinal Chemistry . The authors would like to acknowledge the skillful work of Mr. Mordechai Goldminz and Ms. Gefen Amit. Abraham Rubinstein and Eylon Yavin are affiliated with David R. Bloom Center of Pharmacy.

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

Keywords

Cationized polyacrylamide
Colon cancer
Microbubbles
Real time diagnosis
Recognition peptide
Ultrasound

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ijpharm.2014.11.066

Cite this

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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.",

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author = "Meital Bloch and Lauren Jablonowski and Eylon Yavin and Dorit Moradov and Irena Djavsarov and Abraham Nyska and Margaret Wheatley and Abraham Rubinstein",

note = "Funding Information: The work was supported by a joint research grant from Drexel and HU-IDR and by a research grant from the Alex Grass foundation for Medicinal Chemistry . The authors would like to acknowledge the skillful work of Mr. Mordechai Goldminz and Ms. Gefen Amit. Abraham Rubinstein and Eylon Yavin are affiliated with David R. Bloom Center of Pharmacy. Publisher Copyright: {\textcopyright} 2014, Elsevier B.V. All rights reserved.",

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AU - Bloch, Meital

AU - Jablonowski, Lauren

AU - Yavin, Eylon

AU - Moradov, Dorit

AU - Djavsarov, Irena

AU - Nyska, Abraham

AU - Wheatley, Margaret

AU - Rubinstein, Abraham

N1 - Funding Information: The work was supported by a joint research grant from Drexel and HU-IDR and by a research grant from the Alex Grass foundation for Medicinal Chemistry . The authors would like to acknowledge the skillful work of Mr. Mordechai Goldminz and Ms. Gefen Amit. Abraham Rubinstein and Eylon Yavin are affiliated with David R. Bloom Center of Pharmacy. Publisher Copyright: © 2014, Elsevier B.V. All rights reserved.

PY - 2015/1/30

Y1 - 2015/1/30

N2 - 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.

AB - 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.

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KW - Real time diagnosis

KW - Recognition peptide

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JF - International Journal of Pharmaceutics

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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