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
The role of nonneuronal cells in the resolution of cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial and single-cell transcriptomic profiling of the male mouse brain during the first week of injury. Cortical gene expression was severely disrupted, defined by inflammation and cell death in the lesion core, and glial scar formation orchestrated by multiple cell types on the periphery. The glial scar was identified as a zone with intense cell-cell communication, with prominent ApoE-Trem2 signaling pathway modulating microglial activation. For each of the three major glial populations, an inflammatory-responsive state, resembling the reactive states observed in neurodegenerative contexts, was observed. The recovered spectrum of ischemia-induced oligodendrocyte states supports the emerging hypothesis that oligodendrocytes actively respond to and modulate the neuroinflammatory stimulus. The findings are further supported by analysis of other spatial transcriptomic datasets from different mouse models of ischemic brain injury. Collectively, we present a landmark transcriptomic dataset accompanied by interactive visualization that provides a comprehensive view of spatiotemporal organization of processes in the postischemic mouse brain.
- Klíčová slova
- glia, ischemic stroke, neuroinflammation, single-cell transcriptomics, spatial transcriptomics,
- MeSH
- ischemie mozku * genetika metabolismus patologie MeSH
- membránové glykoproteiny metabolismus genetika MeSH
- mikroglie metabolismus MeSH
- modely nemocí na zvířatech * MeSH
- mozek metabolismus patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neuroglie * metabolismus MeSH
- oligodendroglie metabolismus MeSH
- receptory imunologické MeSH
- signální transdukce MeSH
- stanovení celkové genové exprese MeSH
- transkriptom * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- membránové glykoproteiny MeSH
- receptory imunologické MeSH
- Trem2 protein, mouse MeSH Prohlížeč
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
Despite several attempts, in vivo bimodal imaging still represents a challenge. Generally, it is accepted that dual-modality in imaging can improve sensitivity and spatial resolution, namely, when exploiting fluorescence (FI) and magnetic resonance imaging (MRI), respectively. Here, a newly developed combination of (i) protein-protected luminescent Au-Ag nanoclusters (LGSN) manifesting themselves by fluorescent emission at 705 nm and (ii) superparamagnetic iron oxide nanoparticles (SPION) embedded within the same protein and creating contrast in MR images, has been investigated in phantoms and applied for in vivo bimodal imaging of a mouse as a proof of principle. Unique LGSN-SPION nanocomposites were synthesized in a specific sequential one-pot green preparation procedure and characterized thoroughly using many physicochemical experimental techniques. The influence of LGSN-SPION samples on the viability of healthy cells (RPE-1) was tested using a calcein assay. Despite the presence of Ag (0.12 mg mL-1), high content of Au (above 0.75 mg mL-1), and moderate concentrations of Fe (0.24 mg mL-1), LGSN-SPION samples (containing approx. 15 mg mL-1 of albumin) were revealed as biocompatible (cell viability above 80%). Simultaneously, these concentration values of all components in the LGSN-SPION nanocomposite were used for achieving both MRI and fluorescence signals in phantoms as well as in a living mouse with sufficiently high resolution. Thus, the LGSN-SPION samples can serve as new efficient bimodal FI and MRI probes for in vivo imaging.
- MeSH
- buněčné linie MeSH
- kontrastní látky chemie MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- myši MeSH
- nanokompozity * chemie MeSH
- optické zobrazování MeSH
- stříbro * chemie MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- zlato * chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kontrastní látky MeSH
- stříbro * MeSH
- zlato * MeSH
19F magnetic resonance (19F MR) tracers stand out for their wide range of applications in experimental and clinical medicine, as they can be precisely located in living tissues with negligible fluorine background. This contribution demonstrates the long-term dissolution of multiresponsive fluorinated implants designed for prolonged release. Implants were detected for 14 (intramuscular injection) and 20 (subcutaneous injection) months by 19F MR at 4.7 T, showing favorable MR relaxation times, biochemical stability, biological compatibility and slow, long-term dissolution. Thus, polymeric implants may become a platform for long-term local theranostics.
- Publikační typ
- časopisecké články MeSH
HYPOTHESIS: The development of bimodal imaging probes represents a hot topic of current research. Herein, we deal with developing an innovative bimodal contrast agent enabling fluorescence imaging (FI)/magnetic resonance imaging (MRI) and, simultaneously, consisting of biocompatible nanostructures. Optimized synthesis of advanced protein-embedded bimetallic (APEBM) nanocomposite containing luminescent gold nanoclusters (AuNC) and superparamagnetic iron oxide nanoparticles (SPION), suitable for in vivo dual-modal FI/MR imaging is reported. EXPERIMENTS: The APEBM nanocomposite was prepared by a specific sequential one-pot green synthetic approach that is optimized to increase metals (Au, Fe) content and, consequently, the imaging ability of the resulting nanostructures. The protein matrix, represented by serum albumin, was intentionally chosen, and used since it creates an efficient protein corona for both types of optically/magnetically-susceptible nanostructures (AuNC, SPION) and ensures biocompatibility of the resulting APEBM nanocomposite although it contains elevated metal concentrations (approx. 1 mg·mL-1 of Au, around 0.3 mg·mL-1 of Fe). In vitro and in vivo imaging was performed. FINDINGS: Successful in vivo FI and MRI recorded in healthy mice corroborated the applicability of the APEBM nanocomposite and, simultaneously, served as a proof of concept concerning the potential future exploitation of this new FI/MRI bimodal contrast agent in preclinical and clinical practice.
- Klíčová slova
- Bioimaging, Contrast agent, Fluorescent imaging, Inorganic-organic nanocomposite, Magnetic resonance imaging, Magneto-luminescent nanocomposite,
- MeSH
- kontrastní látky * chemie MeSH
- magnetická rezonanční spektroskopie MeSH
- magnetická rezonanční tomografie metody MeSH
- myši MeSH
- nanokompozity * chemie MeSH
- optické zobrazování MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kontrastní látky * 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.
- Klíčová slova
- clofazimine, fluorine‐19, magnetic resonance, nanoparticles, polymerization‐induced self‐assembly, theranostics,
- 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
- Názvy látek
- biokompatibilní materiály MeSH
- fluor MeSH
- fluorokarbony MeSH
- micely MeSH
In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.
- MeSH
- magnetická rezonanční spektroskopie MeSH
- magnetická rezonanční tomografie * metody MeSH
- polymery * MeSH
- tkáňová distribuce MeSH
- voda MeSH
- železo MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- polymery * MeSH
- voda MeSH
- železo MeSH
Nanocomposites serving as dual (bimodal) probes have great potential in the field of bio-imaging. Here, we developed a simple one-pot synthesis for the reproducible generation of new luminescent and magnetically active bimetallic nanocomposites. The developed one-pot synthesis was performed in a sequential manner and obeys the principles of green chemistry. Briefly, bovine serum albumin (BSA) was exploited to uptake Au (III) and Fe (II)/Fe (III) ions simultaneously. Then, Au (III) ions were transformed to luminescent Au nanoclusters embedded in BSA (AuNCs-BSA) and majority of Fe ions were bio-embedded into superparamagnetic iron oxide nanoparticles (SPIONs) by the alkalization of the reaction medium. The resulting nanocomposites, AuNCs-BSA-SPIONs, represent a bimodal nanoprobe. Scanning transmission electron microscopy (STEM) imaging visualized nanostructures with sizes in units of nanometres that were arranged into aggregates. Mössbauer spectroscopy gave direct evidence regarding SPION presence. The potential applicability of these bimodal nanoprobes was verified by the measurement of their luminescent features as well as magnetic resonance (MR) imaging and relaxometry. It appears that these magneto-luminescent nanocomposites were able to compete with commercial MRI contrast agents as MR displays the beneficial property of bright luminescence of around 656 nm (fluorescence quantum yield of 6.2 ± 0.2%). The biocompatibility of the AuNCs-BSA-SPIONs nanocomposite has been tested and its long-term stability validated.
- Klíčová slova
- MRI assessment, SPION, bovine serum albumin, gold nanocluster, imaging, luminescence material, nanocomposite material,
- Publikační typ
- časopisecké články MeSH
