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
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
The use of fluorinated contrast agents in magnetic resonance imaging (MRI) facilitates improved image quality due to the negligible amount of endogenous fluorine atoms in the body. In this work, we present a comprehensive study of the influence of the amphiphilic polymer structure and composition on its applicability as contrast agents in 19F MRI. Three series of novel fluorine-containing poly(2-oxazoline) copolymers and terpolymers, hydrophilic-fluorophilic, hydrophilic-lipophilic-fluorophilic, and hydrophilic-thermoresponsive-fluorophilic, with block and gradient distributions of the fluorinated units, were synthesized. It was discovered that the CF3 in the 2-(3,3,3-trifluoropropyl)-2-oxazoline (CF3EtOx) group activated the cationic chain end, leading to faster copolymerization kinetics, whereby spontaneous monomer gradients were formed with accelerated incorporation of 2-methyl-2-oxazoline or 2-n-propyl-2-oxazoline with a gradual change to the less-nucleophilic CF3EtOx monomer. The obtained amphiphilic copolymers and terpolymers form spherical or wormlike micelles in water, which was confirmed using transmission electron microscopy (TEM), while small-angle X-ray scattering (SAXS) revealed the core-shell or core-double-shell morphologies of these nanoparticles. The core and shell sizes obey the scaling laws for starlike micelles predicted by the scaling theory. Biocompatibility studies confirm that all copolymers obtained are noncytotoxic and, at the same time, exhibit high sensitivity during in vitro 19F MRI studies. The gradient copolymers provide the best 19F MRI signal-to-noise ratio in comparison with the analogue block copolymer structures, making them most promising as 19F MRI contrast agents.
- MeSH
- difrakce rentgenového záření MeSH
- fluor * MeSH
- maloúhlový rozptyl MeSH
- micely * MeSH
- polymery MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fluor * MeSH
- micely * MeSH
- polymery MeSH
Fluorescent gold nanoclusters (AuNCs) are envisaged as a novel type of fluorophores. This work reports on the first comparative study investigating the effect of presence/absence/abundance of fatty acids (namely palmitic acid, PA) or other substances (like glycoproteins and globulins) in the protein (bovine serum albumin, BSA) on synthesis and properties of the final AuNCs. The most popular template (BSA) and microwave (MW)-assisted synthesis of AuNCs have been intentionally chosen. Our results clearly demonstrate that the fluorescent characteristics (i.e., fluorescence lifetime and quantum yield) are affected by the fatty acids and/or other substances. Importantly, the as-prepared AuNCs are biocompatible, as determined by Alamar Blue assay performed on Hep G2 cell line.
- Klíčová slova
- Au nanocluster, cell viability, fatty acid, palmitic acid, serum albumin,
- Publikační typ
- časopisecké články MeSH
