Synthesis of MIL-Modified Fe3O4 Magnetic Nanoparticles for Enhancing Uptake and Efficiency of Temozolomide in Glioblastoma Treatment.

A nanometric hybrid system consisting of a Fe3O4 magnetic nanoparticles modified through the growth of Fe-based Metal-organic frameworks of the MIL (Materials Institute Lavoiser) was developed. The obtained system retains both the nanometer dimensions and the magnetic properties of the Fe3O4 nanoparticles and possesses increased the loading capability due to the highly porous Fe-MIL. It was tested to load, carry and release temozolomide (TMZ) for the treatment of glioblastoma multiforme one of the most aggressive and deadly human cancers. The chemical characterization of the hybrid system was performed through various complementary techniques: X-ray-diffraction, thermogravimetric analysis, FT-IR and X-ray photoelectron spectroscopies. The nanomaterial showed low toxicity and an increased adsorption capacity compared to bare Fe3O4 magnetic nanoparticles (MNPs). It can load about 12 mg/g of TMZ and carry the drug into A172 cells without degradation. Our experimental data confirm that, after 48 h of treatment, the TMZ-loaded hybrid nanoparticles (15 and 20 µg/mL) suppressed human glioblastoma cell viability much more effectively than the free drug. Finally, we found that the internalization of the MIL-modified system is more evident than bare MNPs at all the used concentrations both in the cytoplasm and in the nucleus suggesting that it can be capable of overcoming the blood-brain barrier and targeting brain tumors. In conclusion, these results indicate that this combined nanoparticle represents a highly promising drug delivery system for TMZ targeting into cancer cells.

Dual-Functional Nano-Functionalized Titanium Scaffolds to Inhibit Bacterial Growth and Enhance Osteointegration.

Implantable biomaterials play a key role for the success of orthopedic surgery procedures. However, infections remain one of the most damaging post-operative complications that lead to the implant failure. Recently, several approaches have been proposed to avoid or manage implant-associated infections. Among these, an appropriate surface functionalization to confer intrinsic antibacterial properties preserving the osteo-integration ability represents an appealing strategy for the development of innovative implant materials. Titanium and its alloys are the most used materials for manufacturing of both articular and bone skull prostheses as well as dental implants. However, to date there is still a significant clinical need to improve their bioactivity, osseointegration and antibacterial activity. In this study, titanium biomimetic scaffolds are prepared by nano-functionalization with TiO2 (Ti_TiO2) and γFe2O3 (Ti_γFe2O3). Both cytocompatibility and antibacterial activity have been evaluated. Data show that both nano-functionalized scaffolds exhibit a good antibacterial activity towards Staphylococcus aureus, reducing colony number to 99.4% (Ti_TiO2) and 99.9% (Ti_γFe2O3), respectively. In addition, an increase of both human adipose-derived mesenchymal stem cells (hADSCs) cell proliferation (up to 4.3-fold for Ti_TiO2 and 3.7-fold for Ti_γFe2O3) and differentiation has been observed. These data suggest that these nano-functionalized titanium substrates represent promising prototypes for new antimicrobial and osteoconductive biomaterials to be used in the orthopedic field to reconstruct significant bone defect.

New Synthetic Route for the Growth of α-FeOOH/NH2-Mil-101 Films on Copper Foil for High Surface Area Electrodes.

A novel metal organic framework (MOF)-based composite was synthesized on a Cu substrate via a two-step route. An amorphous iron oxide/hydroxide layer was first deposited on a Cu foil through a sol-gel process; then, Fe-NH2-Mil-101 was grown using both the iron oxide/hydroxide matrix, which provided the Fe3+ centers needed for MOF formation, and 2-aminoterephthalic acid ethanol solution. This innovative synthetic strategy is a convenient approach to grow metal oxide/hydroxide and MOF composite films. Structural, chemical, and morphological characterizations suggest that the obtained composite is made up of both the α-FeOOH goethite and the NH2-Mil-101 phases featuring a hybrid heterostructure. The electrochemical features of the composite structure were investigated using electrochemical impedance spectroscopy. The impedance behavior of the α-FeOOH/NH2-Mil-101 films indicates that they can be used as efficient high surface area metal hydroxide/MOF-based electrodes for applications such as energy storage and sensing.

Modeling and biological evaluation of 3,3'-(1,2-ethanediyl)bis[2-(4-methoxyphenyl)-thiazolidin-4-one], a new synthetic cyclooxygenase-2 inhibitor.

Within the series of chiral 3,3'-(1,2-ethanediyl)bis[2-arylthiazolidin-4-ones], the 3,4-dimethoxyphenyl substituted derivative was found in the primary anti-inflammatory screening to be endowed with superior in vivo properties and good safety profile. Such a lead compound was modified by eliminating 3-methoxy group while retaining 4-methoxy group on the aryl rings at 2 and 2' stereogenic carbons. The 2R,2'S-meso isomer (VIG3b) of the resulting bisthiazolidinone has been widely investigated. The inhibitory effects on cyclo-oxygenase-1 and cyclo-oxygenase-2 isoenzymes were measured in a human whole blood assay. VIG3b was almost 50 times more selective on the inducible isoform. The cyclo-oxygenase-2 preferential selectivity has been confirmed by modeling VIG3b into the cyclo-oxygenase-1 and cyclo-oxygenase-2 active sites. Furthermore, VIG3b was assayed in the experimental model of carrageenan-induced lung injury by evaluating its ability to inhibit: (1) fluid accumulation in the pleural cavity, (2) neutrophil infiltration, (3) prostaglandin E(2) production and (4) lung injury. VIG3b exhibited interesting activity in all these tests.

In vitro antimycobacterial activities of 2'-monosubstituted isonicotinohydrazides and their cyanoborane adducts.

As a result of our search for new isoniazid derivatives with extended spectra of activity, we evaluated the in vitro antimycobacterial activities of isonicotinohydrazides (compounds 2) and their cyanoborane adducts (compounds 3), both obtained by the reaction of isonicotinoylhydrazones (compounds 1) with sodium cyanoborohydride. Most of the tested compounds displayed moderate to high activity against Mycobacterium tuberculosis H37Rv, with MICs ranging from 0.2 to 12.5 microg/ml. In particular, some hydrazides showed activity similar to that of rifampin (MIC = 0.2 microg/ml) and rather low cytotoxicity, so that they were generally shown to possess high safety indices. In contrast, the coordination to a cyanoborane (BH(2)CN) group (compounds 3) in general brought about a decrease in antimycobacterial activity, while cytotoxicity increased. Interestingly, selected compounds 1 to 3, mostly hydrazides (compounds 2), were effective in killing M. tuberculosis growing within macrophages at concentrations in culture medium which were much lower than the corresponding MICs. These compounds also displayed good activity against drug-resistant M. tuberculosis strains.