Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells

Pawel Misiak,1 Katarzyna Niemirowicz-Laskowska,2 Karolina H Markiewicz,1 Iwona Misztalewska-Turkowicz,1 Przemysław Wielgat,3 Izabela Kurowska,1,4 Gabriela Siemiaszko,1 Mathias Destarac,5 Halina Car,2 Agnieszka Z Wilczewska1 1Faculty of Chemistry, University of Bialystok, Bialystok, Poland; 2Departme...

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Autores principales:	Misiak P, Niemirowicz-Laskowska K, Markiewicz KH, Misztalewska-Turkowicz I, Wielgat P, Kurowska I, Siemiaszko G, Destarac M, Car H, Wilczewska AZ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	cholesterol-end capped poly(n-isopropylacrylamide) cell-penetrating molecules thermoresponsive polymer micelles drug carriers Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/47109fb6d1474f0a946510ca9e0d3b77
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spelling	oai:doaj.org-article:47109fb6d1474f0a946510ca9e0d3b772021-12-02T05:25:13ZEvaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells1178-2013https://doaj.org/article/47109fb6d1474f0a946510ca9e0d3b772020-09-01T00:00:00Zhttps://www.dovepress.com/evaluation-of-cytotoxic-effect-of-cholesterol-end-capped-polyn-isoprop-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Pawel Misiak,1 Katarzyna Niemirowicz-Laskowska,2 Karolina H Markiewicz,1 Iwona Misztalewska-Turkowicz,1 Przemysław Wielgat,3 Izabela Kurowska,1,4 Gabriela Siemiaszko,1 Mathias Destarac,5 Halina Car,2 Agnieszka Z Wilczewska1 1Faculty of Chemistry, University of Bialystok, Bialystok, Poland; 2Department of Experimental Pharmacology, Medical University of Bialystok, Bialystok, Poland; 3Department of Clinical Pharmacology, Medical University of Bialystok, Bialystok, Poland; 4Doctoral School of Exact and Natural Sciences, University of Bialystok, Bialystok, Poland; 5IMRCP, CNRS UMR 5623, Université de Toulouse, Toulouse, FranceCorrespondence: Agnieszka Z Wilczewska; Karolina H Markiewicz Tel +48 85 7388037Email agawilcz@uwb.edu.pl; k.markiewicz@uwb.edu.plPurpose: Efficient intracellular delivery of a therapeutic compound is an important feature of smart drug delivery systems (SDDS). Modification of a carrier structure with a cell-penetrating 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.Keywords: cholesterol-end capped poly(N-isopropylacrylamide), cell-penetrating molecules, thermoresponsive polymer micelles, drug carriersMisiak PNiemirowicz-Laskowska KMarkiewicz KHMisztalewska-Turkowicz IWielgat PKurowska ISiemiaszko GDestarac MCar HWilczewska AZDove Medical Pressarticlecholesterol-end capped poly(n-isopropylacrylamide)cell-penetrating moleculesthermoresponsive polymer micellesdrug carriersMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 7263-7278 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	cholesterol-end capped poly(n-isopropylacrylamide) cell-penetrating molecules thermoresponsive polymer micelles drug carriers Medicine (General) R5-920
spellingShingle	cholesterol-end capped poly(n-isopropylacrylamide) cell-penetrating molecules thermoresponsive polymer micelles drug carriers Medicine (General) R5-920 Misiak P Niemirowicz-Laskowska K Markiewicz KH Misztalewska-Turkowicz I Wielgat P Kurowska I Siemiaszko G Destarac M Car H Wilczewska AZ Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
description	Pawel Misiak,1 Katarzyna Niemirowicz-Laskowska,2 Karolina H Markiewicz,1 Iwona Misztalewska-Turkowicz,1 Przemysław Wielgat,3 Izabela Kurowska,1,4 Gabriela Siemiaszko,1 Mathias Destarac,5 Halina Car,2 Agnieszka Z Wilczewska1 1Faculty of Chemistry, University of Bialystok, Bialystok, Poland; 2Department of Experimental Pharmacology, Medical University of Bialystok, Bialystok, Poland; 3Department of Clinical Pharmacology, Medical University of Bialystok, Bialystok, Poland; 4Doctoral School of Exact and Natural Sciences, University of Bialystok, Bialystok, Poland; 5IMRCP, CNRS UMR 5623, Université de Toulouse, Toulouse, FranceCorrespondence: Agnieszka Z Wilczewska; Karolina H Markiewicz Tel +48 85 7388037Email agawilcz@uwb.edu.pl; k.markiewicz@uwb.edu.plPurpose: Efficient intracellular delivery of a therapeutic compound is an important feature of smart drug delivery systems (SDDS). Modification of a carrier structure with a cell-penetrating 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.Keywords: cholesterol-end capped poly(N-isopropylacrylamide), cell-penetrating molecules, thermoresponsive polymer micelles, drug carriers
format	article
author	Misiak P Niemirowicz-Laskowska K Markiewicz KH Misztalewska-Turkowicz I Wielgat P Kurowska I Siemiaszko G Destarac M Car H Wilczewska AZ
author_facet	Misiak P Niemirowicz-Laskowska K Markiewicz KH Misztalewska-Turkowicz I Wielgat P Kurowska I Siemiaszko G Destarac M Car H Wilczewska AZ
author_sort	Misiak P
title	Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
title_short	Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
title_full	Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
title_fullStr	Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
title_full_unstemmed	Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
title_sort	evaluation of cytotoxic effect of cholesterol end-capped poly(n-isopropylacrylamide)s on selected normal and neoplastic cells
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/47109fb6d1474f0a946510ca9e0d3b77
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Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells

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