Synthesis, Characterization, and Evaluation of Near-IR Boron Dipyrromethene Bioconjugates for Labeling of Adenocarcinomas by Selectively Targeting the Epidermal Growth Factor Receptor

Nichole E.M. Kaufman, Qianli Meng, Kaitlin E. Griffin, Sitanshu S. Singh, Achyut Dahal, Zehua Zhou, Frank R. Fronczek, James Michael Mathis, Seetharama D. Jois, M. Graça H. Vicente

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A series of five boron dipyrromethene (BODIPY) bioconjugates containing an epidermal growth factor receptor (EGFR)-targeted pegylated LARLLT peptide and/or a glucose or biotin ethylene diamine group were synthesized, and the binding capability of the new conjugates to the extracellular domain of EGFR was investigated using molecular modeling, surface plasmon resonance, fluorescence microscopy, competitive binding assays, and animal studies. The BODIPY conjugates with a LARLLT peptide were found to bind specifically to EGFR, whereas those lacking the peptide bound weakly and nonspecifically. All BODIPY conjugates showed low cytotoxicity (IC50 > 94 μM) in HT-29 cells, both in the dark and upon light activation (1.5 J/cm2). Studies of nude mice bearing subcutaneous human HT-29 xenografts revealed that only BODIPY conjugates bearing the LARLLT peptide showed tumor localization 24 h after intravenous administration. The results of our studies demonstrate that BODIPY bioconjugates bearing the EGFR-targeting peptide 3PEG-LARLLT show promise as near-IR fluorescent imaging agents for colon cancers overexpressing EGFR.

Original languageEnglish
Pages (from-to)3323-3335
Number of pages13
JournalJournal of Medicinal Chemistry
Volume62
Issue number7
DOIs
StatePublished - 11 Apr 2019

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leucyl-alanyl-arginyl-leucyl-leucyl-threonine
Boron
Epidermal Growth Factor Receptor
Adenocarcinoma
HT29 Cells
Competitive Binding
Diamines
Surface Plasmon Resonance
Biotin
Fluorescent Dyes
Fluorescence Microscopy
Heterografts
Nude Mice
Intravenous Administration
Colonic Neoplasms
Inhibitory Concentration 50
dipyrromethene
Light
Glucose
Peptides

Cite this

Kaufman, Nichole E.M. ; Meng, Qianli ; Griffin, Kaitlin E. ; Singh, Sitanshu S. ; Dahal, Achyut ; Zhou, Zehua ; Fronczek, Frank R. ; Mathis, James Michael ; Jois, Seetharama D. ; Vicente, M. Graça H. / Synthesis, Characterization, and Evaluation of Near-IR Boron Dipyrromethene Bioconjugates for Labeling of Adenocarcinomas by Selectively Targeting the Epidermal Growth Factor Receptor. In: Journal of Medicinal Chemistry. 2019 ; Vol. 62, No. 7. pp. 3323-3335.
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abstract = "A series of five boron dipyrromethene (BODIPY) bioconjugates containing an epidermal growth factor receptor (EGFR)-targeted pegylated LARLLT peptide and/or a glucose or biotin ethylene diamine group were synthesized, and the binding capability of the new conjugates to the extracellular domain of EGFR was investigated using molecular modeling, surface plasmon resonance, fluorescence microscopy, competitive binding assays, and animal studies. The BODIPY conjugates with a LARLLT peptide were found to bind specifically to EGFR, whereas those lacking the peptide bound weakly and nonspecifically. All BODIPY conjugates showed low cytotoxicity (IC50 > 94 μM) in HT-29 cells, both in the dark and upon light activation (1.5 J/cm2). Studies of nude mice bearing subcutaneous human HT-29 xenografts revealed that only BODIPY conjugates bearing the LARLLT peptide showed tumor localization 24 h after intravenous administration. The results of our studies demonstrate that BODIPY bioconjugates bearing the EGFR-targeting peptide 3PEG-LARLLT show promise as near-IR fluorescent imaging agents for colon cancers overexpressing EGFR.",
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Synthesis, Characterization, and Evaluation of Near-IR Boron Dipyrromethene Bioconjugates for Labeling of Adenocarcinomas by Selectively Targeting the Epidermal Growth Factor Receptor. / Kaufman, Nichole E.M.; Meng, Qianli; Griffin, Kaitlin E.; Singh, Sitanshu S.; Dahal, Achyut; Zhou, Zehua; Fronczek, Frank R.; Mathis, James Michael; Jois, Seetharama D.; Vicente, M. Graça H.

In: Journal of Medicinal Chemistry, Vol. 62, No. 7, 11.04.2019, p. 3323-3335.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Meng, Qianli

AU - Griffin, Kaitlin E.

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AU - Zhou, Zehua

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AU - Mathis, James Michael

AU - Jois, Seetharama D.

AU - Vicente, M. Graça H.

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