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

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 cell-penetrating ligand, ie, cholesterol moiety, is a strategy to improve cellular uptake. Cholesterol end-capped poly(N-isopr...

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Autores principales: Misiak, Pawel, Niemirowicz-Laskowska, Katarzyna, Markiewicz, Karolina H, Misztalewska-Turkowicz, Iwona, Wielgat, Przemysław, Kurowska, Izabela, Siemiaszko, Gabriela, Destarac, Mathias, Car, Halina, Wilczewska, Agnieszka Z
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533236/
https://www.ncbi.nlm.nih.gov/pubmed/33061380
http://dx.doi.org/10.2147/IJN.S262582
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author Misiak, Pawel
Niemirowicz-Laskowska, Katarzyna
Markiewicz, Karolina H
Misztalewska-Turkowicz, Iwona
Wielgat, Przemysław
Kurowska, Izabela
Siemiaszko, Gabriela
Destarac, Mathias
Car, Halina
Wilczewska, Agnieszka Z
author_facet Misiak, Pawel
Niemirowicz-Laskowska, Katarzyna
Markiewicz, Karolina H
Misztalewska-Turkowicz, Iwona
Wielgat, Przemysław
Kurowska, Izabela
Siemiaszko, Gabriela
Destarac, Mathias
Car, Halina
Wilczewska, Agnieszka Z
author_sort Misiak, Pawel
collection PubMed
description 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 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.
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spelling pubmed-75332362020-10-14 Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells Misiak, Pawel Niemirowicz-Laskowska, Katarzyna Markiewicz, Karolina H Misztalewska-Turkowicz, Iwona Wielgat, Przemysław Kurowska, Izabela Siemiaszko, Gabriela Destarac, Mathias Car, Halina Wilczewska, Agnieszka Z Int J Nanomedicine Original Research 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 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. Dove 2020-09-30 /pmc/articles/PMC7533236/ /pubmed/33061380 http://dx.doi.org/10.2147/IJN.S262582 Text en © 2020 Misiak et al. http://creativecommons.org/licenses/by-nc/3.0/ 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).
spellingShingle Original Research
Misiak, Pawel
Niemirowicz-Laskowska, Katarzyna
Markiewicz, Karolina H
Misztalewska-Turkowicz, Iwona
Wielgat, Przemysław
Kurowska, Izabela
Siemiaszko, Gabriela
Destarac, Mathias
Car, Halina
Wilczewska, Agnieszka Z
Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533236/
https://www.ncbi.nlm.nih.gov/pubmed/33061380
http://dx.doi.org/10.2147/IJN.S262582
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