posted on 2025-08-11, 11:26authored byFatma Nalan Cetin, Zulfiya Cernochova, Edward Vermeersch, Vít HerynekVít Herynek, Ondrej Groborz, ewa Pavlova, Miroslav Šlouf, Martin Hruby, Arn Mignon, Richard Hoogenboom, Sandra Van Vlierberghe, Kristyna Kolouchova
<p dir="ltr"><a href="" target="_blank">Theranostic systems that integrate therapeutic delivery with diagnostic imaging hold strong potential in biomedical applications. Nanocarriers with imaging and controlled release functions enable real-time tracking and localization of therapeutics, while hydrogels with diagnostic capabilities support applications such as sustained drug release, cell encapsulation, and cell tracking. Fluorine-19 magnetic resonance imaging (<sup>19</sup>F MRI) is a promising non-invasive complement to conventional proton MRI, though its clinical translation remains limited by the lack of optimal tracer systems. Herein, we report the development of BAB-type triblock copolymers comprising a hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) A block and a thermoresponsive poly[N-(2,2-difluoroethyl)acrylamide] (PDFEA) B block, statistically copolymerized with a ROS-responsive monomer bearing phenylboronic ester groups. These polymers self-assemble into nanoparticles at low concentrations and form thermogelling hydrogels at higher concentrations, allowing for formulation-dependent versatility. The ROS-sensitive component enables disassembly at pathophysiologically relevant ROS levels (~0.4–2 mM), facilitating targeted therapeutic release in oxidative environments such as tumors. The polymers form physically crosslinked nanogels (hydrodynamic radius ≈160–760</a> nm) at 37 °C, which undergo ROS-triggered disassembly. Selected formulations demonstrated excellent <sup>19</sup>F MRI relaxation properties suitable for in vivo imaging. Cytocompatibility was confirmed in vitro using human foreskin fibroblasts. Overall, the developed polymers offer a versatile platform for biomedical applications—ranging from thermogelling injectable hydrogels for drug delivery or cell encapsulation, to nanocarriers for ROS-triggered therapeutic release—all while enabling non-invasive monitoring via <sup>19</sup>F MRI.</p>
Funding
Research Foundation Flanders (FWO) (G075621N, 1SC1225N, K215824N, 1229422N and 1247425N)
Grant Agency of Charles University (GA UK), project No. 199125
Ministry of Education, Youth and Sports of the Czech Republic (grant # LM2023053 EATRIS-CZ)
Ministry of Health of the Czech Republic (grant # NW24-03-00387)
New Technologies for Translational Research in Pharmaceutical Sciences/NETPHARM, project ID CZ.02.01.01/00/22_008/0004607, co-funded by the European Union