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Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors

This report describes the design, synthesis and evaluation of tumor-targeted polymer probes to visualize epidermal growth factor receptor (EGFR)-positive malignant tumors for successful resection via fluorescence guided endoscopic surgery. Fluorescent polymer probes of various molecular weights enab...

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Autores principales: Pola, Robert, Böhmová, Eliška, Filipová, Marcela, Pechar, Michal, Pankrác, Jan, Větvička, David, Olejár, Tomáš, Kabešová, Martina, Poučková, Pavla, Šefc, Luděk, Zábrodský, Michal, Janoušková, Olga, Bouček, Jan, Etrych, Tomáš
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022460/
https://www.ncbi.nlm.nih.gov/pubmed/31906300
http://dx.doi.org/10.3390/pharmaceutics12010031
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author Pola, Robert
Böhmová, Eliška
Filipová, Marcela
Pechar, Michal
Pankrác, Jan
Větvička, David
Olejár, Tomáš
Kabešová, Martina
Poučková, Pavla
Šefc, Luděk
Zábrodský, Michal
Janoušková, Olga
Bouček, Jan
Etrych, Tomáš
author_facet Pola, Robert
Böhmová, Eliška
Filipová, Marcela
Pechar, Michal
Pankrác, Jan
Větvička, David
Olejár, Tomáš
Kabešová, Martina
Poučková, Pavla
Šefc, Luděk
Zábrodský, Michal
Janoušková, Olga
Bouček, Jan
Etrych, Tomáš
author_sort Pola, Robert
collection PubMed
description This report describes the design, synthesis and evaluation of tumor-targeted polymer probes to visualize epidermal growth factor receptor (EGFR)-positive malignant tumors for successful resection via fluorescence guided endoscopic surgery. Fluorescent polymer probes of various molecular weights enabling passive accumulation in tumors via enhanced permeability and retention were prepared and evaluated, showing an optimal molecular weight of 200,000 g/mol for passive tumor targeting. Moreover, poly(N-(2-hydroxypropyl)methacrylamide)-based copolymers labeled with fluorescent dyes were targeted with the EGFR-binding oligopeptide GE-11 (YHWYGYTPQNVI), human EGF or anti-EGFR monoclonal antibody cetuximab were all able to actively target the surface of EGFR-positive tumor cells. Nanoprobes targeted with GE-11 and cetuximab showed the best targeting profile but differed in their tumor accumulation kinetics. Cetuximab increased tumor accumulation after 15 min, whereas GE 11 needed at least 4 h. Interestingly, after 4 h, there were no significant differences in tumor targeting, indicating the potential of oligopeptide targeting for fluorescence-navigated surgery. In conclusion, fluorescent polymer probes targeted by oligopeptide GE-11 or whole antibody are excellent tools for surgical navigation during oncological surgery of head and neck squamous cell carcinoma, due to their relatively simple design, synthesis and cost, as well as optimal pharmacokinetics and accumulation in tumors.
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spelling pubmed-70224602020-03-09 Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors Pola, Robert Böhmová, Eliška Filipová, Marcela Pechar, Michal Pankrác, Jan Větvička, David Olejár, Tomáš Kabešová, Martina Poučková, Pavla Šefc, Luděk Zábrodský, Michal Janoušková, Olga Bouček, Jan Etrych, Tomáš Pharmaceutics Article This report describes the design, synthesis and evaluation of tumor-targeted polymer probes to visualize epidermal growth factor receptor (EGFR)-positive malignant tumors for successful resection via fluorescence guided endoscopic surgery. Fluorescent polymer probes of various molecular weights enabling passive accumulation in tumors via enhanced permeability and retention were prepared and evaluated, showing an optimal molecular weight of 200,000 g/mol for passive tumor targeting. Moreover, poly(N-(2-hydroxypropyl)methacrylamide)-based copolymers labeled with fluorescent dyes were targeted with the EGFR-binding oligopeptide GE-11 (YHWYGYTPQNVI), human EGF or anti-EGFR monoclonal antibody cetuximab were all able to actively target the surface of EGFR-positive tumor cells. Nanoprobes targeted with GE-11 and cetuximab showed the best targeting profile but differed in their tumor accumulation kinetics. Cetuximab increased tumor accumulation after 15 min, whereas GE 11 needed at least 4 h. Interestingly, after 4 h, there were no significant differences in tumor targeting, indicating the potential of oligopeptide targeting for fluorescence-navigated surgery. In conclusion, fluorescent polymer probes targeted by oligopeptide GE-11 or whole antibody are excellent tools for surgical navigation during oncological surgery of head and neck squamous cell carcinoma, due to their relatively simple design, synthesis and cost, as well as optimal pharmacokinetics and accumulation in tumors. MDPI 2020-01-01 /pmc/articles/PMC7022460/ /pubmed/31906300 http://dx.doi.org/10.3390/pharmaceutics12010031 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pola, Robert
Böhmová, Eliška
Filipová, Marcela
Pechar, Michal
Pankrác, Jan
Větvička, David
Olejár, Tomáš
Kabešová, Martina
Poučková, Pavla
Šefc, Luděk
Zábrodský, Michal
Janoušková, Olga
Bouček, Jan
Etrych, Tomáš
Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors
title Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors
title_full Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors
title_fullStr Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors
title_full_unstemmed Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors
title_short Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors
title_sort targeted polymer-based probes for fluorescence guided visualization and potential surgery of egfr-positive head-and-neck tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022460/
https://www.ncbi.nlm.nih.gov/pubmed/31906300
http://dx.doi.org/10.3390/pharmaceutics12010031
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