Ensayo del material compuesto poli-eter-eter-cetona/fibra de carbono en el acetábulo de prótesis totales de cadera

Peer Reviewe

Tuning the endocytosis mechanism of Zr-based metal−organic frameworks through linker functionalization

A critical bottleneck for the use of metal-organic frameworks (MOFs) as drug delivery systems has been allowing them to reach their intracellular targets without being degraded in the acidic environment of the lysosomes. Cells take up particles by endocytosis through multiple biochemical pathways, and the fate of these particles depends on these routes of entry. Here, we show the effect of functional group incorporation into a series of Zr-based MOFs on their endocytosis mechanisms, allowing us to design an effi-cient drug delivery system. In particular, naphthalene-2,6-dicarboxylic acid and 4,4'-biphenyldicarboxylic acid ligands promote entry through the caveolin-pathway, allowing the particles to avoid lysosomal degradation and be delivered into the cytosol, en-hancing their therapeutic activity when loaded with drugs

Discovery of an Optimal Porous Crystalline Material for the Capture of Chemical Warfare Agents

Chemical warfare agents (CWAs) are regarded as a critical challenge in our society. Here, we use a high-throughput computational screening strategy backed up by experimental validation to identify and synthesize a promising porous material for CWA removal under humid conditions. Starting with a database of 2,932 existing metal-organic framework (MOF) structures, we selected those possessing cavities big enough to adsorb well-known CWAs such as sarin, soman, and mustard gas as well as their nontoxic simulants. We used Widom method to reduce significantly the simulation time of water adsorption, allowing us to shortlist 156 hydrophobic MOFs where water will not compete with the CWAs to get adsorbed. We then moved to grand canonical Monte Carlo (GCMC) simulations to assess the removal capacity of CWAs. We selected the best candidates in terms of performance but also in terms of chemical stability and moved to synthesis and experimental breakthrough adsorption to probe the predicted, excellent performance. This computational-experimental work represents a fast and efficient approach to screen porous materials in applications that involve the presence of moisture

Drug delivery and controlled release from biocompatible metal-organic frameworks using mechanical amorphization

We have used a family of Zr-based metal-organic frameworks (MOFs) with different functionalized (bromo, nitro and amino) and extended linkers for drug delivery. We loaded the materials with the fluorescent model molecule calcein and the anticancer drug α-cyano-4-hydroxycinnamic acid (α-CHC), and consequently performed a mechanical amorphization process to attempt to control the delivery of guest molecules. Our analysis revealed that the loading values of both molecules were higher for the MOFs containing unfunctionalized linkers. Confocal microscopy showed that all the materials were able to penetrate into cells, and the therapeutic effect of α-CHC on HeLa cells was enhanced when loaded (20 wt%) into the MOF with the longest linker. On one hand, calcein release required up to 3 days from the crystalline form for all the materials. On the other hand, the amorphous counterparts containing the bromo and nitro functional groups released only a fraction of the total loaded amount, and in the case of the amino-MOF a slow and progressive release was successfully achieved for 15 days. In the case of the materials loaded with α-CHC, no difference was observed between the crystalline and amorphous form of the materials. These results highlight the necessity of a balance between the pore size of the materials and the size of the guest molecules to accomplish a successful and efficient sustained release using this mechanical ball-milling process. Additionally, the endocytic pathway used by cells to internalize these MOFs may lead to diverse final cellular locations and consequently, different therapeutic effects. Understanding these cellular mechanisms will drive the design of more effective MOFs for drug delivery applications.C.A.O. thanks Becas Chile and the Cambridge Trust for funding. D.F.J. thanks the Royal Society (UK) for funding through a University Research Fellowship. RSF thanks the Royal Society for receipt of a University Research Fellowship and the EPSRC (EP/L004461/1) and The University of Glasgow for funding. A.K.C is grateful to the European Research Council for an Advanced Investigator Award

Probing the Mechanochemistry of Metal-Organic Frameworks with Low-Frequency Vibrational Spectroscopy

The identification and characterization of low-frequency vibrational motions of metal-organic frameworks (MOFs) allows for a better understanding of their mechanical and structural response upon perturbation by external stimuli such as temperature, pressure, and adsorption. Here, we describe the combination of an experimental temperature- and pressure-dependent terahertz spectroscopy system with quantum mechanical simulations to measure and assign specific low-frequency vibrational modes that directly drive the mechanochemical properties of this important class of porous materials. More specifically, those intense spectral features in the terahertz region of the vibrational spectrum of ZIF-8 are identified, which are directly connected to its mechanochemical response. In particular, the mechanical compressibility of pristine ZIF-8 is found to follow a peculiar non-linear trend upon pressure: its bulk modulus initially increases up to 0.1 GPa and decreases at higher pressures, which is simultaneously reflected in the terahertz vibrational spectra. This work highlights the interplay between structural, vibrational, and mechanochemical phenomena, all of which are key to the effective exploitation of MOFs. The importance of terahertz vibrational motions on the function of MOFs is demonstrated, and a method presented for their measurement and interpretation, which can be applied widely to any supramolecular material