Nejvíce citovaný článek - PubMed ID 38217510
Self-Assembled Fluorinated Nanoparticles as Sensitive and Biocompatible Theranostic Platforms for 19F MRI
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.
- Publikační typ
- časopisecké články 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
- hydrofobní a hydrofilní interakce MeSH
- kontrastní látky chemie chemická syntéza MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- methakryláty * chemie MeSH
- nádorové buněčné linie MeSH
- nanočástice chemie MeSH
- polyethylenglykoly * chemie MeSH
- polymerizace MeSH
- polymery chemie chemická syntéza MeSH
- zobrazování fluorovou magnetickou rezonancí metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kontrastní látky MeSH
- methakryláty * MeSH
- polyethylene glycol methacrylate MeSH Prohlížeč
- polyethylenglykoly * MeSH
- polymery 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.
- Klíčová slova
- 19F magnetic resonance imaging, 19F magnetic resonance spectroscopy, Cell labeling, Fluorinated micelles,
- MeSH
- barvení a značení metody MeSH
- fantomy radiodiagnostické MeSH
- fluor chemie MeSH
- halogenace MeSH
- kationty * chemie MeSH
- kontrastní látky chemie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- micely * MeSH
- myši MeSH
- viabilita buněk * účinky léků MeSH
- zobrazování fluorovou magnetickou rezonancí metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fluor MeSH
- kationty * MeSH
- kontrastní látky MeSH
- micely * 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
- chytré polymery chemie MeSH
- fluor chemie MeSH
- koncentrace vodíkových iontů MeSH
- kontrastní látky chemie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- polymery chemie MeSH
- zobrazování fluorovou magnetickou rezonancí * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- chytré polymery MeSH
- fluor MeSH
- kontrastní látky MeSH
- polymery MeSH