Facile, productive, and cost-effective synthesis of a novel tetrazine-based iron oxide nanoparticle for targeted image contrast agents and nanomedicines

We have developed an operationally simple, time, and cost-effective protocol to produce a novel tetrazine-based iron oxide nanoparticle using commercially available and inexpensive materials. Our protocol proceeds at room temperature and uses hexafluorophosphate azabenzotriazole tetramethyl uronium, a well-known, widely used reagent for the large-scale industrial production of important pharmaceuticals. The nanoparticles obtained have a diameter range between 16 and 21 nm and showed no toxicity against endothelial cell lines. The tetrazine moiety on the nanoparticle surface could potentially allow further attachment of specific targeting vectors by using so-called copper-free click chemistry. We therefore anticipate that our protocol can represent a significant breakthrough in the future development and commercialization of improved, tissue-specific contrast agents and drug delivery for clinical diagnosis, monitoring and therapy of diseases at an asymptomatic stage

The Bcl-2 repertoire of mesothelioma spheroids underlies acquired apoptotic multicellular resistance.

Three-dimensional (3D) cultures are a valuable platform to study acquired multicellular apoptotic resistance of cancer. We used spheroids of cell lines and actual tumor to study resistance to the proteasome inhibitor bortezomib in mesothelioma, a highly chemoresistant tumor. Spheroids from mesothelioma cell lines acquired resistance to bortezomib by failing to upregulate Noxa, a pro-apoptotic sensitizer BH3-only protein that acts by displacing Bim, a pro-apoptotic Bax/Bak-activator protein. Surprisingly, despite their resistance, spheroids also upregulated Bim and thereby acquired sensitivity to ABT-737, an inhibitor of anti-apoptotic Bcl-2 molecules. Analysis using BH3 profiling confirmed that spheroids acquired a dependence on anti-apoptotic Bcl-2 proteins and were 'primed for death'. We then studied spheroids grown from actual mesothelioma. ABT-737 was active in spheroids grown from those tumors (5/7, ∼70%) with elevated levels of Bim. Using immunocytochemistry of tissue microarrays of 48 mesotheliomas, we found that most (33, 69%) expressed elevated Bim. In conclusion, mesothelioma cells in 3D alter the expression of Bcl-2 molecules, thereby acquiring both apoptotic resistance and sensitivity to Bcl-2 blockade. Mesothelioma tumors ex vivo also show sensitivity to Bcl-2 blockade that may depend on Bim, which is frequently elevated in mesothelioma. Therefore, mesothelioma, a highly resistant tumor, may have an intrinsic sensitivity to Bcl-2 blockade that can be exploited therapeutically

Aluminium matrix composites reinforced by nano Fe \u3c inf\u3e 3 O \u3c inf\u3e 4 doped with TiO \u3c inf\u3e 2 by thermomechanical process

© The Society for Experimental Mechanics, Inc. 2017. In this work, scrap Aluminium Matrix Composites (AMCs) reinforced with 10 wt% nano iron oxide (Fe3O4) were produced and the influence of doping Fe3O4 with TiO2 at 2.5 %, 5 %, 7.5 % and 10 % wt%, was studied. For the dispersion of the reinforcement and the study of the matrix/reinforcement, interface was evaluated by Scanning Electron Microscopy (SEM). Density and microhardness of the composites were measured and compared. Wear and creep response of the composites were evaluated by a nanoindenter, Furthermore modulus and hardness of the composites were calculated using the unloading data from the nanoindentation tests. Relatively homogenous distribution of the constituents, with a good bond between matrix and the reinforcements was observed. It was also observed that wear behaviour improved with the increase in the TiO2 content