A polymer probe based on N-(2-hydroxypropyl)methacrylamide copolymers labelled with a fluorescent dye Dy-633 or Cy-7 and decorated with targeting oligopeptides GE-7 or GE-11, specific targeting ligands binding to epidermal growth factor receptor (EGFR) highly expressed on surface of tumour cells, was designed, synthesised and characterised. Specific accumulation of the polymer probe in the tumour mass is a prerequisite for successful fluorescence-guided endoscopic surgery as the fluorescence signal from the malignant cells enables more precise resection of the tumour without damaging the healthy tissue. Flow cytometry and confocal microscopy was used to assess the binding efficacy of the oligopeptide conjugates to EGFR on the cell membranes of the malignant cells. The results showed that the highest binding efficacy was achieved with polymers bearing the GE-11 targeting oligopeptide in human EGFR-positive hypopharyngeal carcinoma cells (FaDu) and in breast adenocarcinoma cells (MDA-MB-231). Similarly, the polymer probes targeted by the GE-11 oligopeptidewere found in vivo as highly effective in tumour accumulation, as determined from fluorescence imaging. Indeed, the ex vivo cross-section of the tumours showed significant tumour border fluorescence proving the potential of the studied polymer probes. Moreover, the presence of the active targeting moiety on the polymer-drug conjugate should enable the use of such a conjugate as a targeted polymer system for treatment of solid tumours. Replacement of the fluorescent probe with a cytostatic drug provides a targeted polymer nanocancerostatic for advanced treatment of neoplastic diseases, thus the polymer probes have multiple functions.

1st Faculty of Medicine Charles University Prague U Nemocnice 5 120 00 Prague 2 Czechia

BIOPHARM Research Institute of Biopharmacy and Veterinary Drugs a s 254 49 Jilove u Prahy Czechia

Department of Otorhinolaryngology Head and Neck Surgery 1st Faculty of Medicine Charles University and University Hospital Motol 5 Úvalu 84 150 06 Prague 5 Czechia

Institute of Biophysics and Informatics 1st Faculty of Medicine Charles University Salmovská 1 120 00 Prague 2 Czechia

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovského sq 2 162 06 Prague 6 Czechia

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$a Pola, Robert $7 xx0232782 $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 162 06 Prague 6, Czechia (www.imc.cas.cz)

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$a Oligopeptide-targeted polymer nanoprobes for fluorescence-guided endoscopic surgery / $c R Pola, J Parnica, K Zuska, E Böhmová, M Filipová, M Pechar, J Pankrác, J Mucksová, J Kalina, P Trefil, L Šefc, D Větvička, P Poučková, J Bouček, O Janoušková and T Etrych

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$a A polymer probe based on N-(2-hydroxypropyl)methacrylamide copolymers labelled with a fluorescent dye Dy-633 or Cy-7 and decorated with targeting oligopeptides GE-7 or GE-11, specific targeting ligands binding to epidermal growth factor receptor (EGFR) highly expressed on surface of tumour cells, was designed, synthesised and characterised. Specific accumulation of the polymer probe in the tumour mass is a prerequisite for successful fluorescence-guided endoscopic surgery as the fluorescence signal from the malignant cells enables more precise resection of the tumour without damaging the healthy tissue. Flow cytometry and confocal microscopy was used to assess the binding efficacy of the oligopeptide conjugates to EGFR on the cell membranes of the malignant cells. The results showed that the highest binding efficacy was achieved with polymers bearing the GE-11 targeting oligopeptide in human EGFR-positive hypopharyngeal carcinoma cells (FaDu) and in breast adenocarcinoma cells (MDA-MB-231). Similarly, the polymer probes targeted by the GE-11 oligopeptidewere found in vivo as highly effective in tumour accumulation, as determined from fluorescence imaging. Indeed, the ex vivo cross-section of the tumours showed significant tumour border fluorescence proving the potential of the studied polymer probes. Moreover, the presence of the active targeting moiety on the polymer-drug conjugate should enable the use of such a conjugate as a targeted polymer system for treatment of solid tumours. Replacement of the fluorescent probe with a cytostatic drug provides a targeted polymer nanocancerostatic for advanced treatment of neoplastic diseases, thus the polymer probes have multiple functions.

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$a Parnica, J $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 162 06 Prague 6, Czechia (www.imc.cas.cz)

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$a Zuska, K $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 162 06 Prague 6, Czechia (www.imc.cas.cz)

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$a Böhmová, Eliška $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 162 06 Prague 6, Czechia (www.imc.cas.cz) $7 xx0232781

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$a Filipová, M $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 162 06 Prague 6, Czechia (www.imc.cas.cz)

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$a Pechar, Michal, $d 1967- $u First Faculty of Medicine, Charles University Prague, U Nemocnice 5, 120 00, Prague 2, Czechia $7 xx0141621

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$a Pankrác, J $u First Faculty of Medicine, Charles University Prague, U Nemocnice 5, 120 00, Prague 2, Czechia

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$a Mucksová, J $u BIOPHARM, Research Institute of Biopharmacy and Veterinary Drugs, a.s., 254 49 Jilove u Prahy, Czechia

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$a Kalina, J $u BIOPHARM, Research Institute of Biopharmacy and Veterinary Drugs, a.s., 254 49 Jilove u Prahy, Czechia

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$a Trefil, P $u BIOPHARM, Research Institute of Biopharmacy and Veterinary Drugs, a.s., 254 49 Jilove u Prahy, Czechia

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$a Šefc, Luděk, $d 1960- $u First Faculty of Medicine, Charles University Prague, U Nemocnice 5, 120 00, Prague 2, Czechia $7 xx0092587

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$a Větvička, David $u Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Salmovská 1, 120 00, Prague 2, Czechia $7 xx0214483

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$a Poučková, Pavla, $d 1950- $u Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Salmovská 1, 120 00, Prague 2, Czechia $7 jo2002102951

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$a Bouček, Jan, $d 1976- $u Department of Otorhinolaryngology Head and Neck Surgery, First Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, 150 06, Prague 5, Czechia $7 xx0100852

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$a Janoušková, O $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 162 06 Prague 6, Czechia (www.imc.cas.cz)

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$a Etrych, T $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 162 06 Prague 6, Czechia (www.imc.cas.cz)

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