Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(N-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells
Received 21 May 2020
Accepted for publication 30 July 2020
Published 30 September 2020 Volume 2020:15 Pages 7263—7278
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo
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, France
Correspondence: Agnieszka Z Wilczewska; Karolina H Markiewicz Tel +48 85 7388037
Email firstname.lastname@example.org; email@example.com
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.
Keywords: cholesterol-end capped poly(N-isopropylacrylamide), cell-penetrating molecules, thermoresponsive polymer micelles, drug carriers
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. 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.Download Article [PDF] View Full Text [HTML][Machine readable]