Work

Dual thermo- and ROS-responsive triblock copolymers as 19F MRI tracers for functional nanoparticles and hydrogels

Year: 2025

Type: article

Abstract: • Well-defined nanoparticle formation via direct dissolution owing to LCST properties. • Nanogels at physiological temperature which can form physically cross-linked hydrogels. • Excellent ROS-responsive 19 F MRI tracer copolymers with suitable relaxation times even in oxidized state. 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 ( 19 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 nm) at 37 °C, which undergo ROS-triggered disassembly. Selected formulations demonstrated excellent 19 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 19 F-MRI.

Source: European Polymer Journal

DOI: 10.1016/j.eurpolymj.2025.114211