Thermoresponsive Triblock Copolymers as Widely Applicable ¹⁹F Magnetic Resonance Imaging Tracers

Abstract

Fluorine-19 magnetic resonance imaging ( 19 F MRI) has emerged as a promising noninvasive diagnostic tool, broadening the diagnostic possibilities of commonly used proton MRI. Despite the potential of 19 F MRI, an ideal tracer paving the way toward the entry of this method into common medical practice is yet to be developed. In this study, we report on a series of polymeric systems based on thermoresponsive poly[N-(2,2difluoroethyl)acrylamide] (PDFEA), a polymer considered to be an ideal tracer for 19 F MRI. The described systems are designed as BAB triblock copolymers, where B corresponds to thermoresponsive PDFEA blocks and A is a hydrophilic poly(ethylene glycol) block. These BAB triblock copolymers are able to form nanoparticles in dilute aqueous solutions, which undergo a transition into physically cross-linked hydrogels upon increasing the polymer concentration. Since thermoresponsive particle-and hydrogel-based systems are applicable in a wide range of biomedical applications, we created a diagnostic system with potential therapeutic properties (theranostic) as a widely tunable platform through straightforward synthesis while serving a multitude of applications. We analyzed the effect of the BAB block ratio on the self-assembly, thermoresponsiveness, and mechanical properties of the studied hydrogels, together with their suitability for 19 F MRI. Finally, their biocompatibility was assessed on a relevant cell line.

Cell-Interactive Gelatin-Based 19F MRI Tracers: An In Vitro Proof-of-Concept Study

“…20% of fluorine). This result corroborates our previous study, where we demonstrated that DFEA-based nanogels are characterized by a single population of T 1 fluorine relaxation ( T 1 ≈ 450 ms) but 2 populations of T 2 fluorine relaxation ( T 2 ≈ 120 ms and ≈10 ms) . Importantly, the material composition has only a negligible effect on the MR properties of the hydrogels (Section S5.8).…”

“…This result corroborates our previous study, where we demonstrated that DFEA-based nanogels are characterized by a single population of T 1 fluorine relaxation (T 1 ≈ 450 ms) but 2 populations of T 2 fluorine relaxation (T 2 ≈ 120 ms and ≈10 ms). 54 Importantly, the material composition has only a negligible effect on the MR properties of the hydrogels (Section S5.8). 55,56 Regardless of the material composition and properties, in most samples, a vast majority of fluorine atoms exhibited T 2 values higher than 40 ms (usually more than 100 ms; Figure S102).…”

Photoprintable Radiopaque Hydrogels for Regenerative Medicine

“…Increasing the content of AATIPA in the hydrogels increased their G′ values and decreased their SRs in water (Table S13), which is in line with what was described earlier for other small-molecular comonomers. 24,26 This effect likely arises because increasing the content of a small-molecular comonomer decreases the hydrophilicity of the hydrogels, thereby limiting their ability to swell and thereby increasing their mechanical stiffness. In the context of tissue engineering, the G′ values of the hydrogels need to match the G′ values of soft tissues (e.g., adipose tissue, G′ = 0.3−1.3 kPa; intervertebral disk, G′ = 8−93 kPa; prostate, G′ = 6.6−21.9 kPa).…”

Branched Copolymer Surfactants as Versatile Templates for Responsive Emulsifiers with Bespoke Temperature‐Triggered Emulsion‐Breaking or Gelation

“…This approach allowed for the stabilization of the sample morphology at elevated temperatures, which could then be observed using the TEM microscope at laboratory temperature, as documented in previous studies. [37,38] Hot-Stage Light Microscopy of Emulsions: The emulsions were subjected to hot stage light microscopy, with the use of a Nikon Eclipse 80i microscope with a Linkam THMS600 temperature control stage (UK). To begin, a small quantity of the emulsion (which was kept in the refrigerator at 4 °C before the experiment) was placed on a microscope cover glass, followed by another cover glass, and then inserted into the temperature control stage.…”

“…This approach allowed for the stabilization of the sample morphology at elevated temperatures, which could then be observed using the TEM microscope at laboratory temperature, as documented in previous studies. [ 37,38 ]…”