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Tytuł: Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
Autorzy: Misiak, Paweł
Niemirowicz-Laskowska, Katarzyna
Markiewicz, Karolina H.
Misztalewska-Turkowicz, Iwona
Wielgat, Przemysław
Kurowska, Izabela
Siemaszko, Gabriela
Destarac, Mathias
Car, Halina
Wilczewska, Agnieszka Z.
Słowa kluczowe: cholesterol-end capped poly(N-isopropylacrylamide)
cell-penetrating molecules
thermoresponsive polymer micelles
drug carriers
Data wydania: 2020
Data dodania: 4-cze-2024
Wydawca: Dove Medical Press
Źródło: International Journal of Nanomedicine, Vol. 15, 2020, p. 7263-7278
Abstrakt: Purpose: Efficient intracellular delivery of a therapeutic compound is an important feature of smart drug delivery systems (SDDS). Modification of a carrier structure with a cellpenetrating ligand, ie, cholesterol moiety, is a strategy to improve cellular uptake. Cholesterol end-capped poly(N-isopropylacrylamide)s offer a promising foundation for the design of efficient thermoresponsive drug delivery systems. Methods: A series of cholesterol end-capped poly(N-isopropylacrylamide)s (PNIPAAm) with number-average molar masses ranging from 3200 to 11000 g·mol–1 were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization from original xanthate-functionalized cholesterol and self-assembled into micelles. The physicochemical characteristics and cytotoxicity of cholesterol end-capped poly(N-isopropylacrylamide)s have been thoroughly investigated. Results: Phase transition temperature dependence on the molecular weight and hydrophilic/hydrophobic ratio in the polymers were observed in water. Biological test results showed that the obtained materials, both in disordered and micellar form, are non-hemolytic, highly compatible with fibroblasts, and toxic to glioblastoma cells. It was found that the polymer termini dictates the mode of action of the system. Conclusion: The cholesteryl moiety acts as a cell-penetrating agent, which enables disruption of the plasma membrane and in effect leads to the restriction of the tumor growth. Cholesterol end-capped PNIPAAm showing in vitro anticancer efficacy can be developed not only as drug carriers but also as components of combined/synergistic therapy.
Afiliacja: Pawel Misiak - Faculty of Chemistry, University of Bialystok, Bialystok, Poland
Katarzyna Niemirowicz-Laskowska - Department of Experimental Pharmacology, Medical University of Bialystok, Bialystok, Poland
Karolina H. Markiewicz - Faculty of Chemistry, University of Bialystok, Bialystok, Poland
Iwona Misztalewska-Turkowicz - Faculty of Chemistry, University of Bialystok, Bialystok, Poland
Przemysław Wielgat - Department of Clinical Pharmacology, Medical University of Bialystok, Bialystok, Poland;
Izabela Kurowska - Faculty of Chemistry, University of Bialystok, Bialystok, Poland; Doctoral School of Exact and Natural Sciences, University of Bialystok, Bialystok, Poland;
Gabriela Siemiaszko - Faculty of Chemistry, University of Bialystok, Bialystok, Poland
Mathias Destarac - 5IMRCP, CNRS UMR 5623, Université de Toulouse, Toulouse, France
Halina Car - Department of Experimental Pharmacology, Medical University of Bialystok, Bialystok, Poland
Agnieszka Z. Wilczewska - Faculty of Chemistry, University of Bialystok, Bialystok, Poland
E-mail: Agnieszka Z. Wilczewska: agawilcz@uwb.edu.pl
Karolina H. Markiewicz: k.markiewicz@uwb.edu.pl
URI: http://hdl.handle.net/11320/16603
DOI: 10.2147/ijn.s262582
ISSN: 1176-9114
metadata.dc.identifier.orcid: 0000-0002-6882-3519
0000-0002-3311-7147
0000-0002-4857-0489
0000-0001-6191-6053
Typ Dokumentu: Article
metadata.dc.rights.uri: http://creativecommons.org/licenses/by-nc/4.0/
Właściciel praw: © 2020 Misiak et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Występuje w kolekcji(ach):Artykuły naukowe (WChem)

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