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

Authors Misiak P, Niemirowicz-Laskowska K, Markiewicz KH, Misztalewska-Turkowicz I, Wielgat P, Kurowska I, Siemiaszko G, Destarac M, Car H, Wilczewska AZ

Received 21 May 2020

Accepted for publication 30 July 2020

Published 30 September 2020 Volume 2020:15 Pages 7263—7278

DOI https://doi.org/10.2147/IJN.S262582

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 agawilcz@uwb.edu.pl; k.markiewicz@uwb.edu.pl

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

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