TY - JOUR
T1 - Synthesis, Characterization, and Evaluation of Near-IR Boron Dipyrromethene Bioconjugates for Labeling of Adenocarcinomas by Selectively Targeting the Epidermal Growth Factor Receptor
AU - Kaufman, Nichole E.M.
AU - Meng, Qianli
AU - Griffin, Kaitlin E.
AU - Singh, Sitanshu S.
AU - Dahal, Achyut
AU - Zhou, Zehua
AU - Fronczek, Frank R.
AU - Mathis, J. Michael
AU - Jois, Seetharama D.
AU - Vicente, M. Graça H.
N1 - Funding Information:
This work was supported by the National Institutes of Health, grant number R01 CA179902, and the National Science Foundation, grant number 1800126. Notes The authors declare no competing financial interest.
Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/4/11
Y1 - 2019/4/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064228199&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.8b01746
DO - 10.1021/acs.jmedchem.8b01746
M3 - Article
C2 - 30835998
AN - SCOPUS:85064228199
SN - 0022-2623
VL - 62
SP - 3323
EP - 3335
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 7
ER -