In the diagnostics of diabetes, specific targeting of drugs (e.g., liraglutide) to insulin-deficient β-cells with their simultaneous noninvasive imaging is currently needed. In this report, liraglutide (LGL)-conjugated poly(methyl vinyl ether-alt-maleic acid) (PMVEMA)-coated core-shell NaYF4:Yb,Er,Fe@NaYF4:Nd upconversion nanoparticles (CS-UCNPs) have been developed, thoroughly physicochemically characterized, and evaluated in vivo. Novel codoping of Fe2+, Yb3+, and Er3+ ions in the host NaYF4 induced upconversion emission in the red region at both 980 and 808 nm excitation, making the particles suitable for deep-tissue imaging. Surface functionalization with PMVEMA provided colloidal stability and facilitated covalent conjugation with LGL, enabling targeted binding to GLP-1 receptors on pancreatic β-cells, increasing glucose-stimulated insulin secretion from isolated Langerhans islets. Biocompatibility of CS-UCNP@PMVEMA-LGL nanoparticles was confirmed by the trypan blue dye exclusion assay. When the fluorescent dye Flamma was conjugated to the nanoparticles, in vivo fluorescence imaging revealed significantly enhanced accumulation of CS-UCNP@PMVEMA-LGL-Flamma nanoparticles in the pancreas 24 h after intramuscular injection compared with intravenous administration, with luminescence intensity approximately doubled. The improved pancreatic targeting efficiency was attributed to enhanced binding to GLP-1 receptors. Confocal microscopy and elemental analysis confirmed receptor-mediated uptake of the nanoparticles by internalization and their localization within pancreatic β-cells. These findings highlight the potential of CS-UCNP@PMVEMA-LGL nanoparticles as biocompatible targetable imaging agents with future applications in pancreatic diagnostics.

• Klíčová slova
• Flamma, diabetes, liraglutide, nanoparticles, poly(methyl vinyl ether-alt-maleic acid), theranostics, upconversion,
• MeSH
• beta-buňky metabolismus   účinky léků   MeSH
• experimentální diabetes mellitus * farmakoterapie   diagnostické zobrazování   MeSH
• inzulin metabolismus   MeSH
• lidé MeSH
• liraglutid * chemie   farmakologie   MeSH
• maleáty * chemie   MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• polyvinyly chemie   MeSH
• teranostická nanomedicína * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fluoridy MeSH
• inzulin MeSH
• liraglutid * MeSH
• maleáty * MeSH
• polyvinyly MeSH
• sodium yttriumtetrafluoride MeSH Prohlížeč
• ytrium MeSH

Magnetic nanoparticles have been at the center of biomedical research for decades, primarily for their applications in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Superparamagnetic particles, typically based on iron oxide crystals, are effective in both modalities, although each requires distinct magnetic properties for optimal performance. We investigated the performance of nanoparticles based on a nickel-substituted ferrite core and compared them to standard maghemite iron oxide nanoparticles. We synthesized γ-Fe2O3 and Ni x Fe2-x O3 nanoparticles and coated them with a statistical copolymer poly-(N,N-dimethylacrylamide-co-acrylic acid). In vitro testing included X-ray diffraction (XRD), Mössbauer spectroscopy, magnetometry, magnetic resonance relaxometry, magnetic particle spectroscopy, and imaging. In vivo testing involved monitoring of nanoparticle biodistribution using MPI and MRI after intracardial application in a murine model. Mössbauer spectra suggest that the Ni-substituted nanoparticles consist of a stoichiometric NiFe2O4 ferrite and a poorly crystalline antiferromagnetic iron-(III) oxide-hydroxide phase. Amorphous-like impurities in Ni x Fe2-x O3 nanoparticles were probably responsible for lower saturation magnetization than that of γ-Fe2O3 nanoparticles, as was proved by magnetometry, which led to lower r 2 relaxivity. However, MPI revealed a higher signal in the spectrum and superior imaging performance of Ni x Fe2-x O3 compared to γ-Fe2O3 particles, likely due to shorter Néél and Brownian relaxation times. Both types of nanoparticles showed similar performance in bimodal MRI/MPI imaging in vivo. They were detected in the liver immediately after application and appeared in the spleen within 24 h. Long-term localization in the lymph nodes was also observed. Substituting an iron with a nickel ion in the core altered the magnetic properties, leading to lower saturation magnetization and an increased signal in the magnetic particle spectra, which enhanced their performance in MPI. This study demonstrates that γ-Fe2O3 and Ni x Fe2-x O3 nanoparticles are both suitable for combined MRI/MPI imaging; magnetic particle imaging provides a highly specific signal for anatomical magnetic resonance images.

• Klíčová slova
• magnetic particle imaging, magnetic resonance imaging, nickel ferrite nanoparticles, r2 relaxivity, saturation magnetization,
• Publikační typ
• časopisecké články MeSH

Pancreatic cancer is one of the most common forms of malignant disease with a poor survival prognosis. Currently, nanomedicine holds great promise for targeted diagnosis and treatment of this cancer, which also reduces toxic side effects. In this work, we prepared PEG-coated monodisperse upconversion nanoparticles (UCNPs) with a conjugated Flamma® fluorescent dye for imaging and detection of particle distribution in vivo. We performed a thorough physicochemical characterization of the particles and determined their colloidal and chemical stability in several aqueous media such as water, PBS, Dulbecco's modified Eagle's medium and artificial lysosomal fluid. Luminescence resonance energy transfer from the emission of UCNPs as a donor to the Flamma® as an acceptor was confirmed. Intraperitoneal versus intravenous administration was then compared in terms of biodistribution of particles in various organs in the orthotopic mice pancreatic cancer model. The intraperitoneal route was preferred over the intravenous one, because it significantly increased the accumulation of particles in the tumor tissue. These new UCNP@Ale-PEG-Flamma® nanoparticles are thus promising for new treatment avenues for pancreatic cancer.

• Publikační typ
• časopisecké články MeSH

In this study, spherical or hexagonal NaYF4:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells (rat glial tumor cell line) was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real-time proliferation assay. The comet assay was used to determine the oxidative damage of the UCNPs. An in vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. The proliferation assay revealed that the L-UCNPs were less toxic than S-UCNPs. The viability of rMSCs incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. The oxidative damage measured by the comet assay showed that neat L-UCNPs caused more oxidative damage to rMSCs than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.

• Klíčová slova
• biological applications, toxicity, upconverting nanoparticles,
• MeSH
• krysa rodu Rattus MeSH
• mezenchymální kmenové buňky * metabolismus   účinky léků   cytologie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanočástice chemie   MeSH
• oxidační stres účinky léků   MeSH
• polyethylenglykoly chemie   MeSH
• velikost částic MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• polyethylenglykoly MeSH