Fluorine-Containing Block and Gradient Copoly(2-oxazoline)s Based on 2-(3,3,3-Trifluoropropyl)-2-oxazoline: A Quest for the Optimal Self-Assembled Structure for 19F Imaging
Kaberov L.I. Kaberova Z. Murmiliuk A. Trousil J. Sedláček O. Konefal R. Zhigunov A. Pavlova E. Vít M. Jirák D. Hoogenboom R. Filippov S.K.
12 July 2021American Chemical Society
Biomacromolecules
2021#22Issue 72963 - 2975 pp.
The use of fluorinated contrast agents in magnetic resonance imaging (MRI) facilitates improved image quality due to the negligible amount of endogenous fluorine atoms in the body. In this work, we present a comprehensive study of the influence of the amphiphilic polymer structure and composition on its applicability as contrast agents in 19F MRI. Three series of novel fluorine-containing poly(2-oxazoline) copolymers and terpolymers, hydrophilic-fluorophilic, hydrophilic-lipophilic-fluorophilic, and hydrophilic-thermoresponsive-fluorophilic, with block and gradient distributions of the fluorinated units, were synthesized. It was discovered that the CF3 in the 2-(3,3,3-trifluoropropyl)-2-oxazoline (CF3EtOx) group activated the cationic chain end, leading to faster copolymerization kinetics, whereby spontaneous monomer gradients were formed with accelerated incorporation of 2-methyl-2-oxazoline or 2-n-propyl-2-oxazoline with a gradual change to the less-nucleophilic CF3EtOx monomer. The obtained amphiphilic copolymers and terpolymers form spherical or wormlike micelles in water, which was confirmed using transmission electron microscopy (TEM), while small-angle X-ray scattering (SAXS) revealed the core-shell or core-double-shell morphologies of these nanoparticles. The core and shell sizes obey the scaling laws for starlike micelles predicted by the scaling theory. Biocompatibility studies confirm that all copolymers obtained are noncytotoxic and, at the same time, exhibit high sensitivity during in vitro 19F MRI studies. The gradient copolymers provide the best 19F MRI signal-to-noise ratio in comparison with the analogue block copolymer structures, making them most promising as 19F MRI contrast agents.
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Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, Prague, 162 06, Czech Republic
Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Hlavova 8, Prague, 128 40, Czech Republic
Institute for Clinical and Experimental Medicine, Vídeňská 9, Prague, 140 21, Czech Republic
Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 S4, Ghent, B-9000, Belgium
Faculty of Mechatronics Informatics and Interdisciplinary Studies, Technical University of Liberec, Studentská 1402/2, Liberec, 461 17, Czech Republic
Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University in Prague, Salmovská 1, Prague, 120 00, Czech Republic
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, 20520, Finland
Department of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Institute of Macromolecular Chemistry
Department of Physical and Macromolecular Chemistry
Institute for Clinical and Experimental Medicine
Supramolecular Chemistry Group
Faculty of Mechatronics Informatics and Interdisciplinary Studies
Institute of Biophysics and Informatics
Pharmaceutical Sciences Laboratory
Department of Chemistry and Chemical Technology
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