scholarly journals Chondroitin-Sulfate-A-Coated Magnetite Nanoparticles: Synthesis, Characterization and Testing to Predict Their Colloidal Behavior in Biological Milieu

2019 ◽  
Vol 20 (17) ◽  
pp. 4096 ◽  
Author(s):  
Ildikó Y. Tóth ◽  
Erzsébet Illés ◽  
Márta Szekeres ◽  
István Zupkó ◽  
Rodica Turcu ◽  
...  

Biopolymer coated magnetite nanoparticles (MNPs) are suitable to fabricate biocompatible magnetic fluid (MF). Their comprehensive characterization, however, is a necessary step to assess whether bioapplications are feasible before expensive in vitro and in vivo tests. The MNPs were prepared by co-precipitation, and after careful purification, they were coated by chondroitin-sulfate-A (CSA). CSA exhibits high affinity adsorption to MNPs (H-type isotherm). We could only make stable MF of CSA coated MNPs (CSA@MNPs) under accurate conditions. The CSA@MNP was characterized by TEM (size ~10 nm) and VSM (saturation magnetization ~57 emu/g). Inner-sphere metal–carboxylate complex formation between CSA and MNP was proved by FTIR-ATR and XPS. Electrophoresis and DLS measurements show that the CSA@MNPs at CSA-loading > 0.2 mmol/g were stable at pH > 4. The salt tolerance of the product improved up to ~0.5 M NaCl at pH~6.3. Under favorable redox conditions, no iron leaching from the magnetic core was detected by ICP measurements. Thus, the characterization predicts both chemical and colloidal stability of CSA@MNPs in biological milieu regarding its pH and salt concentration. MTT assays showed no significant impact of CSA@MNP on the proliferation of A431 cells. According to these facts, the CSA@MNPs have a great potential in biocompatible MF preparation for medical applications.

2003 ◽  
Vol 789 ◽  
Author(s):  
M. Chastellain ◽  
A. Petri ◽  
H. Hofmann

ABSTRACTNanoscaled particles showing a superparamagnetic behavior have been intensively studied these past years for biomedical applications and water-based ferrofluids turned out to be promising candidates for various in vivo as well as in vitro applications. Nevertheless, the lack of well-defined particles remains an important problem. One of the major challenges is still the large-scale synthesis of particles with a narrow size distribution. In this work iron oxide nanoparticles are obtained by classical co-precipitation in a water-based medium and are subsequently coated with polyvinyl alcohol. The thus obtained ferrofluids are studied and a focus is made on their colloidal stability.


2021 ◽  
Vol 12 (4) ◽  
pp. 045006
Author(s):  
Thoko Malinga ◽  
Tukayi Kudanga ◽  
Londiwe Simphiwe Mbatha

Abstract Bimetallic nanosized delivery systems are attracting a lot of research interest as alternatives to monometallic delivery systems. This study evaluated the ability of bimetallic selenium silver chitosan pegylated folic acid targeted nanoparticles (SeAgChPEGFA NPs) to deliver doxorubicin (DOX) in cervical cancer cells. Comparison studies using monometallic selenium chitosan pegylated folic acid (SeChPEGFA NPs) targeted NPs and free DOX were also conducted. The prepared NPs and their drug nanocomplexes were characterised morphologically and physico-chemically. Drug binding and releasing studies were conducted under a simulated environment in vitro. The cytotoxicity and apoptosis studies were studied using the 3-[(4, 5-dimethylthiazol-2-yl)−2, 5-diphenyl tetrazolium bromide] (MTT) assay and the dual dye staining. The findings revealed that the bimetallic SeAgChPEGFA NPs displayed better colloidal stability, superior physico-chemical qualities, and higher binding abilities in comparison with monometallic SeChPEGFA NPs. In addition, the SeAgChPEGFA NPs showed the pH-triggered controlled drug release and cell-specific cytotoxicity. These findings suggest that the bimetallic NPs are superior delivery systems when compared to their monometallic NPs and free drug counterparts, thus, setting a platform for further in vivo examination.


1997 ◽  
Vol 153 (3) ◽  
pp. 453-464 ◽  
Author(s):  
C H Blomquist ◽  
B S Leung ◽  
C Beaudoin ◽  
D Poirier ◽  
Y Tremblay

Abstract There is growing evidence that various isoforms of 17β-hydroxysteroid dehydrogenase (17-HSD) are regulated at the level of catalysis in intact cells. A number of investigators have proposed that the NAD(P)/NAD(P)H ratio may control the direction of reaction. In a previous study, we obtained evidence that A431 cells, derived from an epidermoid carcinoma of the vulva, are enriched in 17-HSD type 2, a membrane-bound isoform reactive with C18 and C19 17β-hydroxysteroids and 17-ketosteroids. The present investigation was undertaken to confirm the presence of 17-HSD type 2 in A431 cells and to assess intracellular regulation of 17-HSD at the level of catalysis by comparing the activity of homogenates and microsomes with that of cell monolayers. Northern blot analysis confirmed the presence of 17-HSD type 2 mRNA. Exposure of cells to epidermal growth factor resulted in an increase in type 2 mRNA and, for microsomes, increases in maximum velocity (Vmax) with no change in Michaelis constant (Km) for testosterone and androstenedione, resulting in equivalent increases in the Vmax/Km ratio consistent with the presence of a single enzyme. Initial velocity data and inhibition patterns were consistent with a highly ordered reaction sequence in vitro in which testosterone and androstenedione bind only to either an enzyme–NAD or an enzyme–NADH complex respectively. Microsomal dehydrogenase activity with testosterone was 2- to 3-fold higher than reductase activity with androstenedione. In contrast, although cell monolayers rapidly converted testosterone to androstenedione, reductase activity with androstenedione or dehydroepiandrosterone (DHEA) was barely detectable. Lactate but not glucose, pyruvate or isocitrate stimulated the conversion of androstenedione to testosterone by monolayers, suggesting that cytoplasmic NADH may be the cofactor for 17-HSD type 2 reductase activity with androstenedione. However, exposure to lactate did not result in a significant change in the NAD/NADH ratio of cell monolayers. It appears that within A431 cells 17-HSD type 2 is regulated at the level of catalysis to function almost exclusively as a dehydrogenase. These findings give further support to the concept that 17-HSD type 2 functions in vivo principally as a dehydrogenase and that its role as a reductase in testosterone formation by either the Δ4 or Δ5 pathway is limited. Journal of Endocrinology (1997) 153, 453–464


2000 ◽  
Vol 345 (2) ◽  
pp. 297-306 ◽  
Author(s):  
Paulus C. J. VAN DER HOEVEN ◽  
José C. M. VAN DER WAL ◽  
Paula RUURS ◽  
Marc C. M. VAN DIJK ◽  
Wim J. VAN BLITTERSWIJK

14-3-3 Proteins may function as adapters or scaffold in signal-transduction pathways. We found previously that protein kinase C-ζ (PKC-ζ) can phosphorylate and activate Raf-1 in a signalling complex [van Dijk, Hilkmann and van Blitterswijk (1997) Biochem. J. 325, 303-307]. We report now that PKC-ζ-Raf-1 interaction is mediated by 14-3-3 proteins in vitro and in vivo. Co-immunoprecipitation experiments in COS cells revealed that complex formation between PKC-ζ and Raf-1 is mediated strongly by the 14-3-3β and -θ isotypes, but not by 14-3-3ζ. Far-Western blotting revealed that 14-3-3 binds PKC-ζ directly at its regulatory domain, where a S186A mutation in a putative 14-3-3-binding domain strongly reduced the binding and the complex formation with 14-3-3β and Raf-1. Treatment of PKC-ζ with lambda protein phosphatase also reduced its binding to 14-3-3β in vitro. Preincubation of an immobilized Raf-1 construct with 14-3-3β facilitated PKC-ζ binding. Together, the results suggest that 14-3-3 binds both PKC-ζ (at phospho-Ser-186) and Raf-1 in a ternary complex. Complex formation was much stronger with a kinase-inactive PKC-ζ mutant than with wild-type PKC-ζ, supporting the idea that kinase activity leads to complex dissociation. 14-3-3β and -θ were substrates for PKC-ζ, whereas 14-3-3ζ was not. Phosphorylation of 14-3-3β by PKC-ζ negatively regulated their physical association. 14-3-3β with its putative PKC-ζ phosphorylation sites mutated enhanced co-precipitation between PKC-ζ and Raf-1, suggesting that phosphorylation of 14-3-3 by PKC-ζ weakens the complex in vivo. We conclude that 14-3-3 facilitates coupling of PKC-ζ to Raf-1 in an isotype-specific and phosphorylation-dependent manner. We suggest that 14-3-3 is a transient mediator of Raf-1 phosphorylation and activation by PKC-ζ.


2014 ◽  
Vol 96 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Hilke Brühl ◽  
Josef Cihak ◽  
Nicole Goebel ◽  
Yvonne Talke ◽  
Kerstin Renner ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Diana Spiegelberg ◽  
Andris Abramenkovs ◽  
Anja Charlotte Lundgren Mortensen ◽  
Sara Lundsten ◽  
Marika Nestor ◽  
...  

AbstractOncogenic client-proteins of the chaperone Heat shock protein 90 (HSP90) insure unlimited tumor growth and are involved in resistance to chemo- and radiotherapy. The HSP90 inhibitor Onalespib initiates the degradation of oncoproteins, and might also act as a radiosensitizer. The aim of this study was therefore to evaluate the efficacy of Onalespib in combination with external beam radiotherapy in an in vitro and in vivo approach. Onalespib downregulated client proteins, lead to increased apoptosis and caused DNA-double-strands. Monotherapy and combination with radiotherapy reduced colony formation, proliferation and migration assessed in radiosensitive HCT116 and radioresistant A431 cells. In vivo, a minimal treatment regimen for 3 consecutive days of Onalespib (3 × 10 mg/kg) doubled survival, whereas Onalespib with radiotherapy (3 × 2 Gy) caused a substantial delay in tumor growth and prolonged the survival by a factor of 3 compared to the HCT116 xenografted control group. Our results demonstrate that Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy, most prominent in the radiosensitive cell models. We speculate that the depletion and downregulation of client proteins involved in signalling, migration and DNA repair mechanisms is the cause. Thus, individually, or in combination with radiotherapy Onalespib inhibits tumor growth and has the potential to improve radiotherapy outcomes, prolonging the overall survival of cancer patients.


Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3499 ◽  
Author(s):  
Devel ◽  
Almer ◽  
Cabella ◽  
Beau ◽  
Bernes ◽  
...  

Atherosclerosis is a major cardiovascular disease worldwide, that could benefit from innovative nanomedicine imaging tools and treatments. In this perspective, we here studied, by fluorescence imaging in ApoE-/- mice, the biodistribution of non-functionalized and RXP470.1-targeted nanostructured lipid carriers (NLC) loaded with DiD dye. RXP470.1 specifically binds to MMP12, a metalloprotease that is over-expressed by macrophages residing in atherosclerotic plaques. Physico-chemical characterizations showed that RXP-NLC (about 105 RXP470.1 moieties/particle) displayed similar features as non-functionalized NLC in terms of particle diameter (about 60-65 nm), surface charge (about −5 — −10 mV), and colloidal stability. In vitro inhibition assays demonstrated that RXP-NLC conserved a selectivity and affinity profile, which favored MMP-12. In vivo data indicated that NLC and RXP-NLC presented prolonged blood circulation and accumulation in atherosclerotic lesions in a few hours. Twenty-four hours after injection, particle uptake in atherosclerotic plaques of the brachiocephalic artery was similar for both nanoparticles, as assessed by ex vivo imaging. This suggests that the RXP470.1 coating did not significantly induce an active targeting of the nanoparticles within the plaques. Overall, NLCs appeared to be very promising nanovectors to efficiently and specifically deliver imaging agents or drugs in atherosclerotic lesions, opening avenues for new nanomedicine strategies for cardiovascular diseases.


2015 ◽  
Vol 820 ◽  
pp. 335-340 ◽  
Author(s):  
Flávia R.O. Silva ◽  
Nelson B. de Lima ◽  
Deiby S. Gouveia ◽  
Nildemar A.M. Ferreira ◽  
Valter Ussui ◽  
...  

Hydroxyapatite (HA) doped with europium (HAEu) offers the advantage of making the hydroxyapatite a fluorescent biomarker, allowing their imaging through emissionin vivoandin vitrotests. Several authors had been based their studies about europium site occupation (CaI and CaII) in hydroxyapatite by the lanthanide ion luminescence, verifying the influence of the method of synthesis and concentration of the dopant ion. In this study HA nanoparticles doped with 1.4 mol% of trivalent europium were synthesized by co-precipitation method and thermal treated at different temperatures (600°C and 1200°C). A careful evaluation of the influence of the excitation wavelength of europium luminescence in the HAEu was performed and it has been verified that both the characteristics transitions of europium, at CaI and CaII sites, and the luminescent intensity are dependent on the excitation wavelength. The non-observance of this fact can lead to erroneous conclusions about the site occupation of europium in hydroxyapatites.


Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2297
Author(s):  
Khairul Islam ◽  
Manjurul Haque ◽  
Arup Kumar ◽  
Amitra Hoq ◽  
Fahmeed Hyder ◽  
...  

We synthesized manganese ferrite (MnFe2O4) nanoparticles of different sizes by varying pH during chemical co-precipitation procedure and modified their surfaces with polysaccharide chitosan (CS) to investigate characteristics of hyperthermia and magnetic resonance imaging (MRI). Structural features were analyzed by X-ray diffraction (XRD), high-resolution transmission electron microscopy (TEM), selected area diffraction (SAED) patterns, and Mössbauer spectroscopy to confirm the formation of superparamagnetic MnFe2O4 nanoparticles with a size range of 5–15 nm for pH of 9–12. The hydrodynamic sizes of nanoparticles were less than 250 nm with a polydispersity index of 0.3, whereas the zeta potentials were higher than 30 mV to ensure electrostatic repulsion for stable colloidal suspension. MRI properties at 7T demonstrated that transverse relaxation (T2) doubled as the size of CS-coated MnFe2O4 nanoparticles tripled in vitro. However, longitudinal relaxation (T1) was strongest for the smallest CS-coated MnFe2O4 nanoparticles, as revealed by in vivo positive contrast MRI angiography. Cytotoxicity assay on HeLa cells showed CS-coated MnFe2O4 nanoparticles is viable regardless of ambient pH, whereas hyperthermia studies revealed that both the maximum temperature and specific loss power obtained by alternating magnetic field exposure depended on nanoparticle size and concentration. Overall, these results reveal the exciting potential of CS-coated MnFe2O4 nanoparticles in MRI and hyperthermia studies for biomedical research.


2010 ◽  
Vol 9 (1) ◽  
pp. 301 ◽  
Author(s):  
Marco de Bruyn ◽  
Anna A Rybczynska ◽  
Yunwei Wei ◽  
Michael Schwenkert ◽  
Georg H Fey ◽  
...  

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