Four gallium(III) complexes, [Ga(ClQ)3]⋅MeOH (1 - MeOH), [Ga(ClQ)3] (1), [Ga(BrQ)3] (2), [Ga(dIQ)3] (3) and [Ga(CQ)3] (4), were prepared (H-ClQ = 5-chloro-8-quinolinol, H-BrQ = 7-bromo-8-quinolinol, H-dIQ = 5,7-diiodo-8-quinolinol, H-CQ = 5-chloro-7-iodo-8-quinolinol) and characterised by elemental analysis, IR and NMR spectroscopy. Single crystal structure analysis of 1 - MeOH confirmed that the complex has a molecular structure with gallium(III) metal ion coordinated in mer-fashion by N- and O-donor atoms of three ClQ ligands. Stability of all complexes in DMSO was proved by 1H NMR spectroscopy. The in vitro antiproliferative activity of 1 was evaluated against the A2780, MBA-MB-231 and HCT116 cell lines. Complex 1 displays higher antiproliferative activity (IC50 values in the range 2.1-6 μm) compared to the ClQ ligand and cisplatin; and a significant selective antiproliferative potency (IC50 = 136 μm, for normal MRC5pd30 cell line). Radical scavenging experiments revealed that complex 1 exhibits the highest antioxidant activity of the prepared complexes as well as the ligands.
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- antitumorózní látky chemická syntéza farmakologie MeSH
- chinoliny chemická syntéza farmakologie MeSH
- galium chemie MeSH
- komplexní sloučeniny chemická syntéza farmakologie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- scavengery volných radikálů chemická syntéza farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Magnetic nanoparticles of ε-Fe1.76 Ga0.24 O3 with the volume-weighted mean size of 17 nm were prepared by thermal treatment of a mesoporous silica template impregnated with metal nitrates and were coated with silica shell of four different thicknesses in the range 6-24 nm. The bare particles exhibited higher magnetization than the undoped compound, 22.4 Am2 kg-1 at 300 K, and were characterized by blocked state with the coercivity of 1.2 T at 300 K, being thus the very opposite of superparamagnetic iron oxides. The relaxometric study of the silica-coated samples at 0.47 T revealed promising properties for MRI, specifically, transverse relaxivity of 89-168 s-1 mmol(f.u.)-1 L depending on the shell thickness was observed. We investigated the effects of the silica-coated nanoparticles on human A549 and MCF-7 cells. Cell viability, proliferation, cell cycle distribution, and the arrangement of actin cytoskeleton were assessed, as well as formation and maturation of focal adhesions. Our study revealed that high concentrations of silica-coated particles with larger shell thicknesses of 16-24 nm interfere with the actin cytoskeletal networks, inducing thus morphological changes. Consequently, the focal adhesion areas were significantly decreased, resulting in impaired cell adhesion.
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- buněčný cyklus účinky léků MeSH
- buňky A549 MeSH
- cytoskelet účinky léků metabolismus MeSH
- galium chemie farmakologie MeSH
- lidé MeSH
- magnetické nanočástice oxidů železa chemie MeSH
- MFC-7 buňky MeSH
- oxid křemičitý chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In order to compare the coordination properties of 1,4,7-triazacyclononane (tacn) derivatives bearing varying numbers of phosphinic/carboxylic acid pendant groups towards 68Ga, 1,4,7-triazacyclononane-7-acetic-1,4-bis(methylenephosphinic) acid (NOPA) and 1,4,7- triazacyclononane-4,7-diacetic-1-[methylene(2-carboxyethyl)phosphinic] acid (NO2AP) were synthesized using Mannich reactions with trivalent or pentavalent forms of H-phosphinic acids as phosphorus components. Stepwise protonation constants logK1-3 12.06, 3.90 and 1.95, and stability constants with GaIII and CuII, logKGaL 24.01 and logKCuL 16.66, were potentiometrically determined for NOPA. Both ligands were labelled with 68Ga and compared with NOTA (tacn-N,N',N″-triacetic acid) and NOPO, a TRAP-type [tacn-N,N',N″- tris(methylenephosphinic acid)] chelator. At pH 3, NOPO and NOPA showed higher labelling efficiency (binding with lower ligand excess) at both room temperature and 95 °C, compared to NO2AP and NOTA. Labelling efficiency at pH = 0-3 correlated with a number of phosphinic acid pendants: NOPO > NOPA > NO2AP > NOTA; however, it was more apparent at 95 °C than at room temperature. By contrast, NOTA was found to be labelled more efficiently at pH > 4 compared to the ligands with phosphinic acids. Overall, replacement of a single phosphinate donor with a carboxylate does not challenge 68Ga labelling of TRAP-type chelators. However, the presence of carboxylates facilitates labelling at neutral or weakly acidic pH.
RATIONALE: Rare earth-doped sulphide glasses in the Ga-Ge-Sb-S system present radiative emissions from the visible to the middle infrared range (mid-IR) range, which are of interest for a variety of applications including (bio)-chemical optical sensing, light detection, and military counter-measures. The aim of this work was to reveal structural motifs present during the fabrication of thin films by plasma deposition techniques as such knowledge is important for the optimization of thin film growth. METHODS: The formation of clusters in plasma plume from different concentrations of erbium-doped Ga5Ge20Sb10S65 glasses (0.05, 0.1, and 0.5 wt. % of erbium) using laser (337 nm) desorption ionization (LDI) was studied by time-of-flight mass spectrometry (TOF MS) in both positive and negative ion mode. The stoichiometry of the Ga(m)Ge(n)Sb(o)S(p)(+/-) clusters was determined via isotopic envelope analysis and computer modelling. RESULTS: Several Ga(m)Ge(n)Sb(o)S(p)(+/-) singly charged clusters were found but, surprisingly, only four species (Sb3S4(+/-), GaSb2S(p)(+/-) (p = 4, 5), Ga3Sb2S7(+/-) ) were common to both ion modes. For the first time, species containing rare earths (GaSb2SEr(+) and GaS6 Er2(+)) were identified in the plasma formed from rare earth-doped chalcogenide glasses, directly confirming the importance of gallium presence for rare earth bonding within the glassy matrix. CONCLUSIONS: The local structure of Ga-Ge-Sb-S glasses is at least partly different from the structure of species identified in plasma by mass spectrometry, as deduced from Raman scattering spectroscopy analysis; these glasses are mainly formed by [GeS4/2]/[GaS4/2] tetrahedra and [SbS3/2] pyramids. Extended X-ray absorption fine structure measurements show that Er(3+) ions in Ga-Ge-Sb-S glasses are surrounded by 7 sulphur atoms.
Ligands with geminal bis(phosphonic acid) appended to 1,4,7-triazacyclonone-1,4-diacetic acid fragment through acetamide (NOTAM(BP) ) or methylenephosphinate (NO2AP(BP) ) spacers designed for (68) Ga were prepared. Ga(III) complexation is much faster for ligand with methylenephosphinate spacer than that with acetamide one, in both chemical (high reactant concentrations) and radiolabeling studies with no-carrier-added (68) Ga. For both ligands, formation of Ga(III) complex was slower than that with NOTA owing to the strong out-of-cage binding of bis(phosphonate) group. Radiolabeling was efficient and fast only above 60 °C and in a narrow acidity region (pH ~3). At higher temperature, hydrolysis of amide bond of the carboxamide-bis(phosphonate) conjugate was observed during complexation reaction leading to Ga-NOTA complex. In vitro sorption studies confirmed effective binding of the (68) Ga complexes to hydroxyapatite being comparable with that found for common bis(phosphonate) drugs such as pamindronate. Selective bone uptake was confirmed in healthy rats by biodistribution studies ex vivo and by positron emission tomography imaging in vivo. Bone uptake was very high, with SUV (standardized uptake value) of 6.19 ± 1.27 for [(68) Ga]NO2AP(BP) ) at 60 min p.i., which is superior to uptake of (68) Ga-DOTA-based bis(phosphonates) and [(18) F]NaF reported earlier (SUV of 4.63 ± 0.38 and SUV of 4.87 ± 0.32 for [(68) Ga]DO3AP(BP) and [(18) F]NaF, respectively, at 60 min p.i.). Coincidently, accumulation in soft tissue is generally low (e.g. for kidneys SUV of 0.26 ± 0.09 for [(68) Ga]NO2AP(BP) at 60 min p.i.), revealing the new (68) Ga complexes as ideal tracers for noninvasive, fast and quantitative imaging of calcified tissue and for metastatic lesions using PET or PET/CT.
- MeSH
- bisfosfonáty * chemie farmakokinetika farmakologie MeSH
- femur metabolismus radiografie MeSH
- galium * chemie farmakokinetika farmakologie MeSH
- kontrastní látky * chemie farmakokinetika farmakologie MeSH
- krysa rodu rattus MeSH
- pozitronová emisní tomografie metody MeSH
- radioaktivní indikátory * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
