Fluorine magnetic resonance imaging (19F MRI) using polymer tracers overcomes limitations of conventional proton MRI by offering enhanced specificity. However, the lack of systematic comparisons among fluorinated polymers has hindered rational tracer design. In this study, we synthesized an extensive library of water-soluble fluorinated copolymers by varying ratios of hydrophilic and fluorinated monomers and evaluated their 19F MRI properties to identify key structure-property relationships. Optimizing the hydrophilicity of the non-fluorinated comonomer increased fluorine content without compromising water solubility, thereby enhancing the MRI signal. Factors such as chemical structure, molecular interactions, and magnetic relaxation times also significantly influenced tracer performance. The optimized copolymer, poly((N-(2,2,2-trifluoroethyl)acrylamide)60-stat-(N-(2-hydroxyethyl)acrylamide)40), exhibited unprecedented 19F MRI sensitivity with detection limits below 1 mg mL-1, the highest reported to date. We demonstrated the tracer's potential through successful in vivo 19F MRI visualization of solid tumors in mouse models, highlighting its promise for advanced biomedical imaging applications.

• Publication type
• Journal Article MeSH

In recent years, polymerization-induced self-assembly (PISA) has emerged as a powerful method for the straightforward synthesis of polymer nanoparticles at high concentration. In this study, we describe for the first time the synthesis of poly(2-oxazoline) nanoparticles by dispersion cationic ring-opening polymerization-induced self-assembly (CROPISA) in n-dodecane. Specifically, a n-dodecane-soluble aliphatic poly(2-(3-ethylheptyl)-2-oxazoline) (PEHOx) block was chain-extended with poly(2-phenyl-2-oxazoline) (PPhOx). While the PhOx monomer is soluble in n-dodecane, its polymerization leads to n-dodecane-insoluble PPhOx, which leads to in situ self-assembly of the formed PEHOx-b-PPhOx copolymers. The polymerization kinetics and micellization upon second block formation were studied, and diverse nanoparticle dispersions were prepared, featuring varying block lengths and polymer concentrations, leading to dispersions with distinctive morphologies and physical properties. Finally, we developed a single-step protocol for the synthesis of polymer nanoparticles directly from monomers via gradient copolymerization CROPISA, which exploits the significantly greater reactivity of EHOx compared to that of PhOx during the statistical copolymerization of both monomers. Notably, this approach provides access to formulations with monomer compositions otherwise unattainable through the block copolymerization method. Given the synthetic versatility and application potential of poly(2-oxazolines), the developed CROPISA method can pave the way for advanced nanomaterials with favorable properties as demonstrated by using the obtained nanoparticles for stabilization of Pickering emulsions.

• Keywords
• CROP, Copolymerization, Nanoparticles, PISA, Poly(2-oxazoline)s,
• Publication type
• Journal Article MeSH

Amphiphilic gradient copolymers are promising alternatives to block copolymers for self-assembled nanomaterials due to their straightforward synthesis via statistical copolymerization of monomers with different reactivities and hydrophilicity. By carefully selecting monomers, nanoparticles can be synthesized in a single step through gradient copolymerization-induced self-assembly (gPISA). We synthesized highly sensitive 19F MRI nanotracers via aqueous dispersion gPISA of hydrophilic poly(ethylene glycol) methyl ether methacrylate (PEGMA) with core-forming N,N-(2,2,2-trifluoroethyl)acrylamide (TFEAM). The PPEGMA-grad-PTFEAM nanoparticles were optimized to achieve spherical morphology and exceptional 19F MRI performance. Noncytotoxicity was confirmed in Panc-1 cells. In vitro 19F MR relaxometry and imaging demonstrated their diagnostic imaging potential. Notably, these gradient copolymer nanotracers outperformed block copolymer analogs in 19F MRI performance due to their gradient architecture, enhancing 19F relaxivity. The synthetic versatility and superior 19F MRI performance of gradient copolymers highlight their potential in advanced diagnostic imaging applications.

• MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Contrast Media chemistry   chemical synthesis   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Methacrylates * chemistry   MeSH
• Cell Line, Tumor MeSH
• Nanoparticles chemistry   MeSH
• Polyethylene Glycols * chemistry   MeSH
• Polymerization MeSH
• Polymers chemistry   chemical synthesis   MeSH
• Fluorine-19 Magnetic Resonance Imaging methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Contrast Media MeSH
• Methacrylates * MeSH
• polyethylene glycol methacrylate MeSH Browser
• Polyethylene Glycols * MeSH
• Polymers MeSH

Magnetic resonance imaging (MRI) relies on appropriate contrast agents, especially for visualizing transplanted cells within host tissue. In recent years, compounds containing fluorine-19 have gained significant attention as MRI probe, particularly in dual 1H/19F-MR imaging. However, various factors affecting probe sensitivity, such as fluorine content and the equivalency of fluorine atoms, must be considered. In this study, we synthesized fluorinated micelles with adjustable surface positive charge density and investigated their physicochemical properties and MRI efficacy in phantoms and labeled cells. While the micelles exhibited clear signals in 19F-MR spectra and imaging, the concentrations required for MRI visualization of labeled cells were relatively high, adversely affecting cell viability. Despite their favourable physicochemical properties, achieving higher labeling rates without compromising cell viability during labeling remains a challenge for potential in vivo applications.

• Keywords
• 19F magnetic resonance imaging, 19F magnetic resonance spectroscopy, Cell labeling, Fluorinated micelles,
• MeSH
• Staining and Labeling methods   MeSH
• Phantoms, Imaging MeSH
• Fluorine chemistry   MeSH
• Halogenation MeSH
• Cations * chemistry   MeSH
• Contrast Media chemistry   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Micelles * MeSH
• Mice MeSH
• Cell Survival * drug effects   MeSH
• Fluorine-19 Magnetic Resonance Imaging methods   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Fluorine MeSH
• Cations * MeSH
• Contrast Media MeSH
• Micelles * MeSH

Fluorine magnetic resonance imaging (19F MRI) is a rapidly evolving research area with a high potential to advance the field of clinical diagnostics. In this review, we provide an overview of the recent progress in the field of fluorinated stimuli-responsive polymers applied as 19F MRI tracers. These polymers respond to internal or external stimuli (e.g., temperature, pH, oxidative stress, and specific molecules) by altering their physicochemical properties, such as self-assembly, drug release, and polymer degradation. Incorporating noninvasive 19F labels enables us to track the biodistribution of such polymers. Furthermore, by triggering polymer transformation, we can induce changes in 19F MRI signals, including attenuation, amplification, and chemical shift changes, to monitor alterations in the environment of the tracer. Ultimately, this review highlights the emerging potential of stimuli-responsive fluoropolymer 19F MRI tracers in the current context of polymer diagnostics research.

• MeSH
• Stimuli Responsive Polymers chemistry   MeSH
• Fluorine chemistry   MeSH
• Hydrogen-Ion Concentration MeSH
• Contrast Media chemistry   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Polymers chemistry   MeSH
• Fluorine-19 Magnetic Resonance Imaging * methods   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Stimuli Responsive Polymers MeSH
• Fluorine MeSH
• Contrast Media MeSH
• Polymers MeSH