Newly Synthesized CoFe2-xDyxO4 (x = 0; 0.1; 0.2; 0.4) Nanoparticles Reveal Promising Anticancer Activity against Melanoma (A375) and Breast Cancer (MCF-7) Cells.

The current study focuses on the synthesis via combustion of dysprosium-doped cobalt ferrites that were subsequently physicochemically analyzed in terms of morphological and magnetic properties. Three types of doped nanoparticles were prepared containing different Dy substitutions and coated with HPGCD for higher dispersion properties and biocompatibility, and were later submitted to biological tests in order to reveal their potential anticancer utility. Experimental data obtained through FTIR, XRD, SEM and TEM confirmed the inclusion of Dy3+ ions in the nanoparticles' structure. The size of the newly formed nanoparticles ranged between 20 and 50 nm revealing an inverse proportional relationship with the Dy content. Magnetic studies conducted by VSM indicated a decrease in remanent and saturation mass magnetization, respectively, in Dy-doped nanoparticles in a direct proportionality with the Dy content; the decrease was further amplified by cyclodextrin complexation. Biological assessment in the presence/absence of red light revealed a significant cytotoxic activity in melanoma (A375) and breast (MCF-7) cancer cells, while healthy keratinocytes (HaCaT) remained generally unaffected, thus revealing adequate selectivity. The investigation of the underlying cytotoxic molecular mechanism revealed an apoptotic process as indicated by nuclear fragmentation and shrinkage, as well as by Western blot analysis of caspase 9, p53 and cyclin D1 proteins. The anticancer activity for all doped Co ferrites varied was in a direct correlation to their Dy content but without being affected by the red light irradiation.

Nucleic Acid Probes in Bio-Imaging and Diagnostics: Recent Advances in ODN-Based Fluorescent and Surface-Enhanced Raman Scattering Nanoparticle and Nanostructured Systems.

Raman nanoparticle probes are a potent class of optical labels for the interrogation of pathological and physiological processes in cells, bioassays, and tissues. Herein, we review the recent advancements in fluorescent and Raman imaging using oligodeoxyribonucleotide (ODN)-based nanoparticles and nanostructures, which show promise as effective tools for live-cell analysis. These nanodevices can be used to investigate a vast number of biological processes occurring at various levels, starting from those involving organelles, cells, tissues, and whole living organisms. ODN-based fluorescent and Raman probes have contributed to the achievement of significant advancements in the comprehension of the role played by specific analytes in pathological processes and have inaugurated new possibilities for diagnosing health conditions. The technological implications that have emerged from the studies herein described could open new avenues for innovative diagnostics aimed at identifying socially relevant diseases like cancer through the utilization of intracellular markers and/or guide surgical procedures based on fluorescent or Raman imaging. Particularly complex probe structures have been developed within the past five years, creating a versatile toolbox for live-cell analysis, with each tool possessing its own strengths and limitations for specific studies. Analyzing the literature reports in the field, we predict that the development of ODN-based fluorescent and Raman probes will continue in the near future, disclosing novel ideas on their application in therapeutic and diagnostic strategies.

SI-ATRP Decoration of Magnetic Nanoparticles with PHEMA and Post-Polymerization Modification with Folic Acid for Tumor Cells' Specific Targeting.

Targeted nanocarriers could reach new levels of drug delivery, bringing new tools for personalized medicine. It is known that cancer cells overexpress folate receptors on the cell surface compared to healthy cells, which could be used to create new nanocarriers with specific targeting moiety. In addition, magnetic nanoparticles can be guided under the influence of an external magnetic field in different areas of the body, allowing their precise localization. The main purpose of this paper was to decorate the surface of magnetic nanoparticles with poly(2-hydroxyethyl methacrylate) (PHEMA) by surface-initiated atomic transfer radical polymerization (SI-ATRP) followed by covalent bonding of folic acid to side groups of the polymer to create a high specificity magnetic nanocarrier with increased internalization capacity in tumor cells. The biocompatibility of the nanocarriers was demonstrated by testing them on the NHDF cell line and folate-dependent internalization capacity was tested on three tumor cell lines: MCF-7, HeLa and HepG2. It has also been shown that a higher concentration of folic acid covalently bound to the polymer leads to a higher internalization in tumor cells compared to healthy cells. Last but not least, magnetic resonance imaging was used to highlight the magnetic properties of the functionalized nanoparticles obtained.

Novel Lanthanide (III) Complexes Derived from an Imidazole-Biphenyl-Carboxylate Ligand: Synthesis, Structure and Luminescence Properties.

A series of neutral mononuclear lanthanide complexes [Ln(HL)2(NO3)3] (Ln = La, Ce, Nd, Eu, Gd, Dy, Ho) with rigid bidentate ligand, HL (4'-(1H-imidazol-1-yl)biphenyl-4-carboxylic acid) were synthesized under solvothermal conditions. The coordination compounds have been characterized by infrared spectroscopy, thermogravimetry, powder X-ray diffraction and elemental analysis. According to X-ray diffraction, all the complexes are a series of isostructural compounds crystallized in the P2/n monoclinic space group. Additionally, solid-state luminescence measurements of all complexes show that [Eu(HL)2(NO3)3] complex displays the characteristic emission peaks of Eu(III) ion at 593, 597, 615, and 651 nm.

Nitrogen-Based Linkers with a Mesitylene Core: Synthesis and Characterization.

Mesitylene was used as a core in seven new tritopic nitrogen containing linkers. Three of the linkers, each containing three nitrile groups, were obtained through Suzuki, Sonogashira and Heck-type coupling reactions. Next, these were converted to tetrazol-5-yl moieties by the cycloaddition of sodium azide to the nitrile functionalities. The last linker, containing three 1,2,3-triazol-4-yl moieties, was synthesized by the Huisgen cycloaddition of phenyl azide to the corresponding alkyne. The latter was obtained via a Corey-Fuchs reaction sequence from the previously reported formyl derivative. As the proof of concept for their potential in MOF design, one of the nitriles was used to build an Ag-based network.

New Microporous Lanthanide Organic Frameworks. Synthesis, Structure, Luminescence, Sorption, and Catalytic Acylation of 2-Naphthol.

New metal-organic frameworks (MOF) with lanthanum(III), cerium(III), neodymium(III), europium(III), gadolinium(III), dysprosium(III), and holmium(III)] and the ligand precursor 1,3,5-tris(4-carboxyphenyl)-2,4,6-trimethylbenzene (H3L) were synthesized under solvothermal conditions. Single crystal x-ray analysis confirmed the formation of three-dimensional frameworks of [LnL(H2O)2]n·xDMF·yH2O for Ln = La, Ce, and Nd. From the nitrogen sorption experiments, the compounds showed permanent porosity with Brunauer-Emmett-Teller (BET) surface areas of about 400 m2/g, and thermal stability up to 500 °C. Further investigations showed that these Ln-MOFs exhibit catalytic activity, paving the way for potential applications within the field of catalysis.

Mass Spectrometry as a Complementary Approach for Noncovalently Bound Complexes Based on Cyclodextrins.

An important and well-designed solution to overcome some of the problems associated with new drugs is provided by the molecular encapsulation of the drugs in the cyclodextrins (CDs) cavity, yielding corresponding inclusion complexes (ICs). These types of non-covalent complexes are of current interest to the pharmaceutical industry, as they improve the solubility, stability and bioavailability of the guest molecules. This review highlights several methods for cyclodextrin ICs preparation and characterization, focusing mostly on the mass spectrometry (MS) studies that have been used for the detection of noncovalent interactions of CDs inclusion complexes and binding selectivity of guest molecules with CDs. Furthermore, the MS investigations of several ICs of the CD with antifungal, antioxidants or fluorescent dyes are presented in greater details, pointing out the difficulties overcome in the analysis of this type of compounds.

Etiologic Agents and Antifungal Susceptibility of Oral Candidosis from Romanian patients with HIV-infection or type 1 diabetes mellitus.

This is the first Romanian investigation of oral candidosis in patients suffering of HIV-infection or type 1 diabetes mellitus (T1DM). Candida albicans was the dominant species in both types of isolates: n = 14 (46.7%) in T1DM, n = 60 (69.8%) in HIV. The most frequent non-albicans Candida spp. were Candida kefyr (n = 6; 20%) in T1DM and Candida dubliniensis (n = 8; 9.3%) in HIV. Resistance to fluconazole was detected only in the HIV non-albicans Candida group (n = 8; 9.3%). All isolates were susceptible to VOR. The experimental drug MXP had MIC values equal or close to the ones of VOR. Echinocandin resistance was more frequent than azole resistance.

Low toxicity ß-cyclodextrin-caged 4,4'-bipyridinium-bis(siloxane): synthesis and evaluation.

The toxicity of viologens can be significantly reduced by including them in tight [2]rotaxane structures alongside ß-cyclodextrin, thus turning them into candidates of pharmaceutical interest. Here, we report a synthesis pathway for a benign viologen, by capping a small ß-cyclodextrin-caged molecule, the 4,4'-bipyridine, with minimal-length presynthesized axle-stopper segments of the propyl-3-pentamethyldisiloxane type. After 90 min from the oral administration to laboratory mice, the product concentration in the bloodstream reaches a value equivalent to 0.634% of the initial dose of 800 mg·kg(-1). As compared to the nude viologen having the same structure, which proved to be lethal in doses of 40 mg·kg(-1), the product induces reversible morphological changes in the liver, kidney, lung, and cerebellum, up to a dose of 400 mg·kg(-1), with higher dosages giving rise to a chronic slow evolution.

Complexes of Ibuprofen Thiazolidin-4-One Derivatives with ß-Cyclodextrin: Characterization and In Vivo Release Profile and Biological Evaluation.

Generally, NSAIDs are weakly soluble in water and contain both hydrophilic and hydrophobic groups. One of the most widely used NSAIDs is ibuprofen, which has a poor solubility and high permeability profile. By creating dynamic, non-covalent, water-soluble inclusion complexes, cyclodextrins (CDs) can increase the dissolution rate of low aqueous solubility drugs, operating as a drug delivery vehicle, additionally contributing significantly to the chemical stability of pharmaceuticals and to reducing drug-related irritability. In order to improve the pharmacological and pharmacokinetics profile of ibuprofen, new thiazolidin-4-one derivatives of ibuprofen (4b, 4g, 4k, 4m) were complexed with ß-CD, using co-precipitation and freeze-drying. The new ß-CD complexes (ß-CD-4b, ß-CD-4g, ß-CD-4k, ß-CD-4m) were characterized using scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and a phase solubility test. Using the AutoDock-VINA algorithm included in YASARA-structure software, we investigated the binding conformation of ibuprofen derivatives to ß-CD and measured the binding energies. We also performed an in vivo biological evaluation of the ibuprofen derivatives and corresponding ß-CD complexes, using analgesic/anti-inflammatory assays, as well as a release profile. The results support the theory that ß-CD complexes (ß-CD-4b, ß-CD-4g, ß-CD-4k, ß-CD-4m) have a similar effect to ibuprofen derivatives (4b, 4g, 4k, 4m). Moreover, the ß-CD complexes demonstrated a delayed release profile, which provides valuable insights into the drug-delivery area, focused on ibuprofen derivatives.

Theoretical study on ß-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole.

The synthesis of the ß-cyclodextrin/propiconazole nitrate inclusion complex and the advantages of the encapsulation of this drug were recently reported, but the experimental data only partially revealed the structure of the supramolecular complex due to the limitations in understanding the intermolecular association mechanism. The present work describes the equilibrium molecular geometries of ß-cyclodextrin/propiconazole and ß-cyclodextrin/protonated propiconazole, established by the AM1 and PM3 semi-empirical methods. The affinity between different parts of the guest molecule and the cyclodextrin cavity was studied considering that propiconazole possesses three residues able to be included into the host cavity through primary or secondary hydroxyl rims. The results have revealed that the most stable complex is formed when the azole residue of the propiconazole enters the cavity of the cyclodextrin through the narrow hydroxyl's rim.

Polysiloxane ionic liquids as good solvents for ß-cyclodextrin-polydimethylsiloxane polyrotaxane structures.

An ionic liquid based on polydimethylsiloxane with imidazolium salt brushes was synthesized as a good solvent for ß-cyclodextrin-polydimethylsiloxane rotaxane. As expected the PDMS-Im/Br ionic liquid had a liquid-like non-Newtonian behavior with rheological parameters dependent on frequency and temperature. The addition of rotaxane to the ionic liquid strengthened the non-Newtonian character of the sample and a type of stable liquid-like network was formed due to the contribution of weak ionic interactions. The structure is stable in the 20 to 80 °C domain as proved by the oscillatory and rotational rheological tests.

Multifunctional magnetic cargo-complexes with radical scavenging properties.

Core-shell magnetic nanoparticle synthesis offers the opportunity to engineering their physical properties for specific applications when the intrinsic magnetic properties can be associated with other interesting ones. The purpose of this study was to design, synthesize, and characterize core-shell magnetic nanoparticles that mimic superoxide dismutase activity offering the possibility of guidance and therapeutic action. We proposed, for the first time, the synthesis and characterization of the nanocarriers comprised of magnetite nanoparticles functionalized with branched polyethyleneimine of low molecular weight (1.8 kDa) permitting the loading of the protocatechuic acid or its inclusion complex with anionic sulfobutylether-ß-cyclodextrin for active drug delivery, in order to combine the useful properties of the magnetite and the protocatechuic acid antioxidant effect. NMR and DSC analyses confirmed the formation of the inclusion complex between sulfobutylether-ß-cyclodextrin and protocatechuic acid, while structural and compositional analyses (FT-IR, TEM, XRD) revealed the synthesis of the multifunctional magnetic systems. Due to the possibility of being formulated as blood system injectable suspensions, antioxidant activity (using DPPH test) and cytotoxicity (using MTS assay on normal human dermal fibroblasts cells) were also measured, showing adequate properties to be used in biomedical applications. Moreover, we proposed a nanocarrier that would be able to load unstable active principles and with very low solubility in biological fluids to increase their biological ability.

Aqueous Dispersion of Single-Walled Carbon Nanotubes Using Tetra-Phenyl Bimesitylene Derivative via Noncovalent Modification and Improved Antimicrobial Activity.

Tetra-arylbimesityl derivative containing carboxylic groups have successfully been utilized in dispersing single-walled carbon nanotubes (SWNTs) in aqueous solutions through sonication and centrifugation procedures. The dispersion process and the characterization of final stabilized SWNTs were accomplished using analytical techniques, providing sufficient evidences on the preparation of the dispersed SWNTs in water. All the prepared SWNT water dispersions were evaluated for antimicrobial activity against three different reference strains namely Escherichia coli, Staphylococcus aureus and Candida albicans, and have shown considerable selective activity against the Gram-positive strain Staphylococcus aureus.

ß-Cyclodextrin as a Functional Excipient Used for Enhancing the Diminazene Aceturate Bioavailability.

In this study, we proposed formulations of diminazene aceturate (DA) designed to improve its bioavailability and to maximize the therapeutic index in animals by overcoming the rapid degradation under the acidic pH of the stomach. An important consequence is the fact that its amount in the bloodstream is close to the administered dose. This was made possible by incorporating DA into the ß-cyclodextrin's (ßCD) cavity in a molar ratio of 1:1. The structure of the resulted inclusion complex was established by Raman, DSC, and Wide-Angle X ray Diffraction (WAXD) in solid state and by 1H-NMR and H-H ROESY in aqueous solutions. The stoichiometry of the DA:ßCD inclusion complex was obtained by using the continuous variation method (Job's plot), considering the chemical shifts variations of protons from both DA and ßCD compounds in 1H-NMR spectra. The biological activity was estimated in vitro by antioxidant activity and in vivo by comparing the bioavailability of parent DA and its inclusion complexes after a single dose administration in Wistar rats by using the HPLC method on their blood plasma. In vitro tests showed an improved antioxidant activity. In vivo tests have shown that the DA concentration is always much higher in blood plasma of rats when DA:ßCD inclusion complex of 1:1 molar ratio was administered (i.e., at 60 min, DA is around 11 and 3 times higher when DA:ßCD inclusion complex of 1:1 molar ratio was administered than the parent DA one and DA:ßCD lyophilized mixture of 1:2 molar ratio, respectively).

An original method for producing acetaldehyde and diacetyl by yeast fermentation.

In this study a natural culture medium that mimics the synthetic yeast peptone glucose medium used for yeast fermentations was designed to screen and select yeasts capable of producing high levels of diacetyl and acetaldehyde. The presence of whey powder and sodium citrate in the medium along with manganese and magnesium sulfate enhanced both biomass and aroma development. A total of 52 yeasts strains were cultivated in two different culture media, namely, yeast peptone glucose medium and yeast acetaldehyde-diacetyl medium. The initial screening of the strains was based on the qualitative reaction of the acetaldehyde with Schiff's reagent (violet color) and diacetyl with Brady's reagent (yellow precipitate). The fermented culture media of 10 yeast strains were subsequently analyzed by gas chromatography to quantify the concentration of acetaldehyde and diacetyl synthesized. Total titratable acidity values indicated that a total titratable acidity of 5.5°SH, implying culture medium at basic pH, was more favorable for the acetaldehyde biosynthesis using strain D15 (Candida lipolytica; 96.05mgL-1 acetaldehyde) while a total titratable acidity value of 7°SH facilitated diacetyl flavor synthesis by strain D38 (Candida globosa; 3.58mgL-1 diacetyl). Importantly, the results presented here suggest that this can be potentially used in the baking industry.

An original method for producing acetaldehyde and diacetyl by yeast fermentation

Abstract In this study a natural culture medium that mimics the synthetic yeast peptone glucose medium used for yeast fermentations was designed to screen and select yeasts capable of producing high levels of diacetyl and acetaldehyde. The presence of whey powder and sodium citrate in the medium along with manganese and magnesium sulfate enhanced both biomass and aroma development. A total of 52 yeasts strains were cultivated in two different culture media, namely, yeast peptone glucose medium and yeast acetaldehyde-diacetyl medium. The initial screening of the strains was based on the qualitative reaction of the acetaldehyde with Schiff's reagent (violet color) and diacetyl with Brady's reagent (yellow precipitate). The fermented culture media of 10 yeast strains were subsequently analyzed by gas chromatography to quantify the concentration of acetaldehyde and diacetyl synthesized. Total titratable acidity values indicated that a total titratable acidity of 5.5 °SH, implying culture medium at basic pH, was more favorable for the acetaldehyde biosynthesis using strain D15 (Candida lipolytica; 96.05 mg L-1 acetaldehyde) while a total titratable acidity value of 7 °SH facilitated diacetyl flavor synthesis by strain D38 (Candida globosa; 3.58 mg L-1 diacetyl). Importantly, the results presented here suggest that this can be potentially used in the baking industry.

Inclusion complex of a new propiconazole derivative with ß-cyclodextrin: NMR, ESI-MS and preliminary pharmacological studies.

A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with ß-cyclodextrin (ß-CD) was prepared by treatment of propiconazole (PCZ) with an acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with ß-CD has been studied by NMR, ESI-MS, TGA, DSC methods. Using the undecoupled signal in the HMBC correlation spectra, almost identical coupling constants of CH from trizolic ring of PCZ and NO3PCZ compounds ((1)J(HC)3=207 Hz, (1)J(CH)5=214 Hz, for PCZ; (1)J(HC)3=208 Hz and (1)J(CH)5=215 Hz, for NO3PCZ) were determined, confirming that the geometry of the heterocyclic skeleton is identical in both the forms. The 1:1 stoichiometry of the complex was determined by ESI-MS and was confirmed using Scott's equation in DMSO and Higuchi and Connors equation in water. The solubility curve obtained for NO3PCZ in presence of ß-CD in distilled water was constructed, resulting in a solubility diagram of AL type. Solubility of NO3PCZ in water was determined by DLS studies. The results showed that NO3PCZ was encapsulated within the ß-CD cavity with a binding constant of 330 M-1 in DMSO and 975 M-1 in water. Preliminary pharmacological studies showed higher antifungal activities for NO3PCZ and its inclusion complex, compared with its PCZ analog. The acute toxicity of the complex is smaller than the pure or modified drug, recommending the inclusion complex as future promising therapeutic agents.