Oligopeptide-targeted polymer nanoprobes for fluorescence-guided endoscopic surgery

0506036 - ÚMCH 2020 RIV GB eng J - Journal Article
Pola, Robert - Parnica, Jozef - Zuska, Kryštof - Böhmová, Eliška - Filipová, Marcela - Pechar, Michal - Pankrác, J. - Mucksová, J. - Kalina, J. - Trefil, P. - Šefc, L. - Větvička, D. - Poučková, P. - Bouček, J. - Janoušková, Olga - Etrych, Tomáš
Oligopeptide-targeted polymer nanoprobes for fluorescence-guided endoscopic surgery.
Multifunctional Materials. Roč. 2, č. 2 (2019), s. 1-13, č. článku 024004. ISSN 2399-7532
R&D Projects: GA MZd(CZ) NV16-28594A; GA MPO(CZ) FV10370; GA ČR(CZ) GA16-17207S; GA ČR(CZ) GA17-13283S; GA MŠMT(CZ) LO1507
Institutional support: RVO:61389013
Keywords : polymer carrier * endoscopic surgery * peptide targeting
OECD category: Polymer science
Method of publishing: Limited access
https://iopscience.iop.org/article/10.1088/2399-7532/ab159e

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.
Permanent Link: http://hdl.handle.net/11104/0306641