302 stran : grafy, tabulky ; 23 cm
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.
- 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
Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring-the dichloro[(±)-trans-N,N'-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC50 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC50 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC50 values in the lower micromolar region.
- MeSH
- buňky Hep G2 MeSH
- DNA metabolismus chemie MeSH
- fluor chemie MeSH
- komplexní sloučeniny * farmakologie chemie chemická syntéza MeSH
- lidé MeSH
- ligandy MeSH
- měď * chemie MeSH
- protinádorové látky * farmakologie chemie MeSH
- Schiffovy báze * chemie farmakologie MeSH
- sérový albumin hovězí chemie MeSH
- ureasa antagonisté a inhibitory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Theranostics is a novel paradigm integrating therapy and diagnostics, thereby providing new prospects for overcoming the limitations of traditional treatments. In this context, perfluorocarbons (PFCs) are the most widely used tracers in preclinical fluorine-19 magnetic resonance (19F MR), primarily for their high fluorine content. However, PFCs are extremely hydrophobic, and their solutions often display reduced biocompatibility, relative instability, and subpar 19F MR relaxation times. This study aims to explore the potential of micellar 19F MR imaging (MRI) tracers, synthesized by polymerization-induced self-assembly (PISA), as alternative theranostic agents for simultaneous imaging and release of the non-steroidal antileprotic drug clofazimine. In vitro, under physiological conditions, these micelles demonstrate sustained drug release. In vivo, throughout the drug release process, they provide a highly specific and sensitive 19F MRI signal. Even after extended exposure, these fluoropolymer tracers show biocompatibility, as confirmed by the histological analysis. Moreover, the characteristics of these polymers can be broadly adjusted by design to meet the wide range of criteria for preclinical and clinical settings. Therefore, micellar 19F MRI tracers display physicochemical properties suitable for in vivo imaging, such as relaxation times and non-toxicity, and high performance as drug carriers, highlighting their potential as both diagnostic and therapeutic tools.
- MeSH
- biokompatibilní materiály chemie MeSH
- fluor chemie MeSH
- fluorokarbony chemie MeSH
- halogenace MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- micely MeSH
- myši MeSH
- nanočástice * chemie terapeutické užití MeSH
- teranostická nanomedicína * MeSH
- zobrazování fluorovou magnetickou rezonancí * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We developed a multifunctional polymer coating for nanoparticles (NPs) that enables simultaneous detection by 19F MRI and shielding from blood plasma fouling. The coating is based on a water-soluble fluorinated poly(N-(2-fluoroethyl)acrylamide) (PFEAM) that shows high 19F MRI sensitivity, cytocompatibility and excellent antifouling properties, significantly outperforming polyethylene glycol. A proof-of-concept experiment was performed by synthesizing polymer-coated gold NPs that were successfully visualized by 19F MRI at magnetic fields close to the fields used in clinical practice. This universal approach can be used for coating and tracing of various NPs upon suitable polymer chain-end modification.
- MeSH
- akrylové pryskyřice chemie farmakologie MeSH
- biokompatibilní potahované materiály chemie farmakologie MeSH
- bioznečištění prevence a kontrola MeSH
- fluor MeSH
- halogenace MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- nanostruktury chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Magnetic resonance imaging (MRI) using 19F-based tracers has emerged as a promising multi-purpose noninvasive diagnostic tool and its application requires the use of various 19F-based tracers for the intended diagnostic purpose. In this study, we report a series of double-stimuli-responsive polymers for use as injectable implants, which were designed to form implants under physiological conditions, and to subsequently dissolve with different dissolution rates (t1/2 ranges from 30 to more than 250 days). Our polymers contain a high concentration of fluorine atoms, providing remarkable signal detectability, and both a hydrophilic monomer and a pH-responsive monomer that alter the biodistribution properties of the implant. The implant location and dissolution were observed using 19F MRI, which allows the anatomic extent of the implant to be monitored. The dissolution kinetics and biocompatibility of these materials were thoroughly analyzed. No sign of toxicity in vitro or in vivo or pathology in vivo was observed, even in chronic administration. The clinical applicability of our polymers was further confirmed via imaging of a rat model by employing an instrument currently used in human medicine.
PURPOSE: Combining specific and quantitative F-19 magnetic resonance imaging (MRI) with sensitive and convenient optical imaging provides complementary information about the distribution and viability of transplanted pancreatic islet grafts. In this study, pancreatic islets (PIs) were labeled with positively charged multimodal nanoparticles based on poly(lactic-co-glycolic acid) (PLGA-NPs) with encapsulated perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green. PROCEDURES: One thousand and three thousand bioluminescent PIs were transplanted into subcutaneous artificial scaffolds, which served as an alternative transplant site. The grafts were monitored using in vivo F-19 MR, fluorescence, and bioluminescence imaging in healthy rats for 2 weeks. RESULTS: Transplanted PIs were unambiguously localized in the scaffolds by F-19 MRI throughout the whole experiment. Fluorescence was detected in the first 4 days after transplantation only. Importantly, in vivo bioluminescence correlated with the F-19 MRI signal. CONCLUSIONS: We developed a trimodal imaging platform for in vivo examination of transplanted PIs. Fluorescence imaging revealed instability of the fluorescent dye and its limited applicability for longitudinal in vivo studies. A correlation between the bioluminescence signal and the F-19 MRI signal indicated the fast clearance of PLGA-NPs from the transplantation site after cell death, which addresses a major issue with intracellular imaging labels. Therefore, the proposed PLGA-NP platform is reliable for reflecting the status of transplanted PIs in vivo.
- MeSH
- endocytóza MeSH
- fluor chemie MeSH
- fluorescence MeSH
- Langerhansovy ostrůvky diagnostické zobrazování MeSH
- luminiscenční měření * MeSH
- magnetická rezonanční tomografie * MeSH
- modely u zvířat MeSH
- molekulární zobrazování * MeSH
- potkani inbrední LEW MeSH
- potkani transgenní MeSH
- přežití tkáně MeSH
- tkáňové podpůrné struktury chemie MeSH
- transplantace Langerhansových ostrůvků * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Over the last few years, the development and relevance of 19F magnetic resonance imaging (MRI) for use in clinical practice has emerged. MRI using fluorinated probes enables the achievement of a specific signal with high contrast in MRI images. However, to ensure sufficient sensitivity of 19F MRI, fluorine probes with a high content of chemically equivalent fluorine atoms are required. The majority of 19F MRI agents are perfluorocarbon emulsions, which have a broad range of applications in molecular imaging, although the content of fluorine atoms in these molecules is limited. In this review, we focus mainly on polymer probes that allow higher fluorine content and represent versatile platforms with properties tailorable to a plethora of biomedical in vivo applications. We discuss the chemical development, up to the first imaging applications, of these promising fluorine probes, including injectable polymers that form depots that are intended for possible use in cancer therapy.
- MeSH
- fluor chemie MeSH
- fluorokarbony chemie MeSH
- koncentrace vodíkových iontů MeSH
- kontrastní látky chemie MeSH
- lidé MeSH
- molekulární sondy chemie MeSH
- molekulární zobrazování přístrojové vybavení metody MeSH
- myši MeSH
- polymery chemie MeSH
- radiační rozptyl MeSH
- reaktivní formy kyslíku metabolismus MeSH
- světlo MeSH
- teplota MeSH
- zobrazování fluorovou magnetickou rezonancí metody trendy MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: 19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested. METHODS: Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T. RESULTS: 19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe. CONCLUSION: DOTP-based 19F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.
- MeSH
- chelátory chemie MeSH
- fluor chemie MeSH
- ionty MeSH
- kontrastní látky chemie MeSH
- krysa rodu rattus MeSH
- lanthanoidy chemie MeSH
- ligandy MeSH
- magnetismus MeSH
- molekulová hmotnost MeSH
- oxazoly chemie MeSH
- pyrimidinony chemie MeSH
- zobrazování fluorovou magnetickou rezonancí * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Colloidal-chemical characteristics of block/branched cationic and non-ionic polyamphiphiles containing poly(fluorine-alkyl methacrylate) (poly(FMA)) block and their intermolecular complexes with biopolymers were studied. The dependences of their surface activity and micelle size on the length of hydrophobic and hydrophilic blocks, as well as the length of side fluorine-alkyl branches were established. Poly(FMA)-block-poly(DMAEMA) was used for formation of interpolyelectrolyte complexes with plasmid DNA (pDNA) via their electrostatic interaction. Novel non-viral polyplexes were tested as gene delivery systems for mammalian cells. The results of DLS, TEM and MALDI-ToF studies demonstrated disaggregation of lysozyme (LYZ) aggregates in the presence of poly(FMA)-block-poly(NVP) and formation of the polyamphiphile…LYS complex possessing antibacterial action.
- MeSH
- DNA chemie metabolismus MeSH
- fluor chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- methakryláty chemie MeSH
- micely MeSH
- muramidasa chemie metabolismus MeSH
- plazmidy chemie metabolismus MeSH
- polyethylenglykoly chemie MeSH
- polymery chemie metabolismus MeSH
- technika přenosu genů MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
