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Pharmaceutics
Volume 12
Issue 1
10.3390/pharmaceutics12010031
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Article

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

by
Robert Pola
1,
Eliška Böhmová
1,
Marcela Filipová
1,
Michal Pechar
1,
Jan Pankrác
2,
David Větvička
3,
Tomáš Olejár
3,
Martina Kabešová
3,
Pavla Poučková
3,
Luděk Šefc
2,
Michal Zábrodský
4,
Olga Janoušková
1,
Jan Bouček
4,* and
Tomáš Etrych
1,*
1
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 162 06 Prague 6, Czech Republic
2
Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, U Nemocnice 5, 120 00 Prague 2, Czech Republic
3
Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Salmovská 1, 120 00 Prague 2, Czech Republic
4
Department of Otorhinolaryngology Head and Neck Surgery, First Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, 150 06 Prague 5, Czech Republic
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 31; https://doi.org/10.3390/pharmaceutics12010031
Received: 5 November 2019 / Revised: 11 December 2019 / Accepted: 19 December 2019 / Published: 1 January 2020
(This article belongs to the Special Issue Advanced Polymeric Delivery Systems for Cancer Therapy)
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Abstract

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. View Full-Text
Keywords: fluorescence; polymeric conjugate; guided surgery; HPMA; tumor; Head and Neck carcinoma fluorescence; polymeric conjugate; guided surgery; HPMA; tumor; Head and Neck carcinoma
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Pola, R.; Böhmová, E.; Filipová, M.; Pechar, M.; Pankrác, J.; Větvička, D.; Olejár, T.; Kabešová, M.; Poučková, P.; Šefc, L.; Zábrodský, M.; Janoušková, O.; Bouček, J.; Etrych, T. Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors. Pharmaceutics 2020, 12, 31. https://doi.org/10.3390/pharmaceutics12010031

AMA Style

Pola R, Böhmová E, Filipová M, Pechar M, Pankrác J, Větvička D, Olejár T, Kabešová M, Poučková P, Šefc L, Zábrodský M, Janoušková O, Bouček J, Etrych T. Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors. Pharmaceutics. 2020; 12(1):31. https://doi.org/10.3390/pharmaceutics12010031

Chicago/Turabian Style

Pola, Robert, Eliška Böhmová, Marcela Filipová, Michal Pechar, Jan Pankrác, David Větvička, Tomáš Olejár, Martina Kabešová, Pavla Poučková, Luděk Šefc, Michal Zábrodský, Olga Janoušková, Jan Bouček, and Tomáš Etrych. 2020. "Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors" Pharmaceutics 12, no. 1: 31. https://doi.org/10.3390/pharmaceutics12010031

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