Impact of Single-Walled Carbon Nanotube Functionalization on Ion and Water Molecule Transport at the Nanoscale.

Nanofluidics has a very promising future owing to its numerous applications in many domains. It remains, however, very difficult to understand the basic physico-chemical principles that control the behavior of solvents confined in nanometric channels. Here, water and ion transport in carbon nanotubes is investigated using classical force field molecular dynamics simulations. By combining one single walled carbon nanotube (uniformly charged or not) with two perforated graphene sheets, we mimic single nanopore devices similar to experimental ones. The graphitic edges delimit two reservoirs of water and ions in the simulation cell from which a voltage is imposed through the application of an external electric field. By analyzing the evolution of the electrolyte conductivity, the role of the carbon nanotube geometric parameters (radius and chirality) and of the functionalization of the carbon nanotube entrances with OH or COO- groups is investigated for different concentrations of group functions.

Nanovectorization of Ivermectin to avoid overdose of drugs.

Ivermectin is an antiparasitic drug that results in the death of the targeted parasites using several mechanical actions. While very well supported, it can induce in rare cases, adverse effects including coma and respiratory failure in case of overdose. This problem should be solved especially in an emergency situation. For instance, the first pandemic of the 21th century was officially declared in early 2020, and while several vaccines around the worlds have been used, an effective treatment against this new strain of coronavirus, better known as SARS-CoV-2, should also be considered, especially given the massive appearance of variants. From all the tested therapies, Ivermectin showed a potential reduction of the viral portability, but sparked significant debate around the dose needed to achieve these positive results. To answer this general question, we propose, using simulations, to show that the nanovectorization of Ivermectin on BN oxide nanosheets can increase the transfer of the drug to its target and thus decrease the quantity of drug necessary to cope with the disease. This first application could help science to develop such nanocargo to avoid adverse effects.Communicated by Ramaswamy H. Sarma.

Gold modification by reduction of a diazonium salt prepared from an aliphatic diamine: a new useful means to remove hazardous substances.

We studied the electrochemical reduction based on gold electrode of a diazonium salt prepared from ethylenediamine. This is the first time where the covalent functionalization on the gold electrode of an alkyldiazonium salt, 2-aminoethane-1-diazonium chloride, is demonstrated. This step requires the preparation beforehand by diazotization of one amine group from ethylenediamine. The resulting electrodeposited ethylamine film was confirmed by spectroscopic characterizations from gold surface modification monitored by electrochemical quartz crystal microbalance (EQCM) coupled to cyclic voltammetry (CV). The development of chemosensors based on such a covalent functionalization of a metal can reduce the chemical threats to human health along with drastically removing contaminants according to the green chemistry principles.

ePTFE-based biomedical devices: An overview of surgical efficiency.

Polytetrafluoroethylene (PTFE) is a ubiquitous material used for implants and medical devices in general because of its high biocompatibility and inertness: blood vessel, heart, table jawbone, nose, eyes, or abdominal wall can benefit from its properties in case of disease or injury. Its expanded version, ePTFE is an improved version of PTFE with better mechanical properties, which extends its medical applications. A material as frequently used as ePTFE with these exceptional properties deserves a review of its main uses, developments, and possibility of improvements. In this systematic review, we examined clinical trials related to ePTFE-based medical devices from the literature. Then, we excluded all trials using ePTFE as a control to test other devices. ePTFE-coated stents, hemodialysis and bypass grafts, guided bone and tissue regeneration membranes, hernia and heart repair and other devices are reviewed. The rates of success using these devices and their efficiency compared to other materials used for the same purposes are reported. ePTFE appears to be more or just as efficient compared to them. Some success rates remain low, suggesting the need of improvement ePTFE for medical applications.

Growth, pigment changes, and photosystem II activity in the aquatic macrophyte Lemna minor exposed to bisphenol A.

As a result of its high production, bisphenol A (BPA) has become ubiquitous in aquatic and terrestrial habitats. In this study, we investigated the toxicity of BPA at 10 mg L-1 on Lemna minor after 7 days of exposure under controlled conditions according to ISO 20079. BPA statistically reduced the total frond number and frond area, while frond number per colony was significantly elevated in BPA-treated group. However, no change was recorded in root number, while root length was significantly reduced by BPA. BPA also decreased the content of Chl a, Chl b, Chl a + b, and carotenoid by 36%, 44%, 38%, and 32%, respectively, versus the control leading to a decrease in the quantum yield of photosystem II. In addition, non-photochemical quenching (NPQ) values were 2.4- and 4.5-fold higher in light than in dark conditions for control and BPA-treated plants, respectively. Thus, there is a significant activation (61.8%; p<0.01) of PSII photoprotection mechanism (NPQ) in BPA-treated plants compared to control but without removing the negative effect of BPA on PSII. The total amount of soluble sugars was reduced by 40% compared to control, and starch accumulation was mainly observed in fronds exposed to BPA. Even if the response patterns of Lemna minor based on fresh and dry weight measurements were less sensitive in our experiment conditions, further studies should be addressed since BPA represents a threat to the dynamic equilibrium governing aquatic ecosystems.

Breaking the Controversy of the Electropolymerization of Pyrrole Mechanisms by the Effective Screening Medium Quantum Charged Model Interface.

Several mechanisms for the electropolymerization of pyrrole have been proposed since the first report 40 years ago. However, none of them were consensual despite a range of assumptions. We simulated and explained the preliminary steps governing the electropolymerization of pyrrole in a charged model interface using first-principles molecular dynamics calculations to solve the problem. We have shown under these conditions that adjacent pyrrole molecules in water can react together, causing their electropolymerization at the interface with a biased platinum electrode in anodic oxidation. In this work, the effective screening medium method that prevents energy divergence of the system was applied to different configurations of pyrrole, water, and electrolyte molecules to best screen the phase space. Furthermore, we worked on a Pt(100) electrode surface in an aqueous electrolyte to be as close as possible to the experimental conditions, MD taking the average of their different orientations.

From Behavior of Water on Hydrophobic Graphene Surfaces to Ultra-Confinement of Water in Carbon Nanotubes.

In recent years and with the achievement of nanotechnologies, the development of experiments based on carbon nanotubes has allowed to increase the ionic permeability and/or selectivity in nanodevices. However, this new technology opens the way to many questionable observations, to which theoretical work can answer using several approximations. One of them concerns the appearance of a negative charge on the carbon surface, when the latter is apparently neutral. Using first-principles density functional theory combined with molecular dynamics, we develop here several simulations on different systems in order to understand the reactivity of the carbon surface in low or ultra-high confinement. According to our calculations, there is high affinity of the carbon atom to the hydrogen ion in every situation, and to a lesser extent for the hydroxyl ion. The latter can only occur when the first hydrogen attack has been achieved. As a consequence, the functionalization of the carbon surface in the presence of an aqueous medium is activated by its protonation, then allowing the reactivity of the anion.

A potential solution to avoid overdose of mixed drugs in the event of Covid-19: Nanomedicine at the heart of the Covid-19 pandemic.

Since 2020, the world is facing the first global pandemic of 21st century. Among all the solutions proposed to treat this new strain of coronavirus, named SARS-CoV-2, the vaccine seems a promising way but the delays are too long to be implemented quickly. In the emergency, a dual therapy has shown its effectiveness but has also provoked a set of debates around the dangerousness of a particular molecule, hydroxychloroquine. In particular, the doses to be delivered, according to the studies, were well beyond the acceptable doses to support the treatment without side effects. We propose here to use all the advantages of nanovectorization to address this question of concentration. Using quantum and classical simulations we will show in particular that drug transport on boron nitrogen oxide nanosheets increases the effectiveness of the action of these drugs. This will definitely allow to decrease the drug quantity needing to face the disease.

Ligand nanovectorization using graphene to target cellular death receptors of cancer cell.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is nowadays envisaged as a natural cytokine useful in nanomedicine to eradicate the cancer cells and not the healthy surrounding ones. However, it suffers from cell resistance and strong dispersion in body to prove its efficiency. The understanding at the molecular level of the TRAIL interaction with death receptors (DRs) on cancer cells is thus of fundamental importance to improve its action. We demonstrate here via molecular simulations that TRAIL can bind to its both agonistic DRs (ie, DR4 and DR5) with a preference for DR4. In this study, the role of a graphene nanoflake as a potential cargo for TRAIL is examined. Furthermore, both TRAIL self-assembling and TRAIL affinity when adsorbed on graphene are considered to enhance efficacy toward the targeted cancer cell. Our modelization results show that TRAIL can bind to DR4 and DR5 when transported by graphene nanoflake, as a proof of concept.

From Anodic Oxidation of Aliphatic α-Amino Acids to Polypeptides by Quantum Electrochemistry Approach: Beyond Miller-Urey Experiments.

For years, polypeptide formation has fascinated the scientific world because its understanding could lead to one of the possible explanations for the origin of life. Anodic oxidation of aliphatic α-amino acids in aqueous electrolytes can result either in their decomposition or in their polymerization into polypeptide. This behavior depends experimentally on both amino acid concentration and pH. The elucidation of the involved mechanisms remains a challenge because of the multitude of products which can be obtained. In this context, the electrochemical behavior of glycine and alanine on a biased platinum surface was examined at the nanoscale by quantum electrochemistry via the effective screening medium method. Several electrochemical systems with different concentrations and pH values have been explored. Simulations of the anodic oxidation of the amino acids have not only confirmed their electropolymerization and decomposition at high and low concentrations, respectively, but also have revealed unsuspected mechanisms at the origin of polypeptide formation. This sheds new light on electrochemistry of α-amino acids, on occurrence of polypeptides, and more generally on organic electrochemistry.

Controlled modification of electrochemical microsystems with polyethylenimine/reduced graphene oxide using electrophoretic deposition: Sensing of dopamine levels in meat samples.

Microsystems play an important role in many biological and environmental applications. The integration of electrical interfaces into such miniaturized systems provides new opportunities for electrochemical sensing where high sensitivity and selectivity towards the analyte are requested. This can be only achieved upon controlled functionalization of the working electrode, a challenge for compact microsystems. In this work, we demonstrate the benefit of electrophoretic deposition (EPD) of reduced graphene oxide/polyethylenimine (rGO/PEI) for the selective modification of a gold (Au) microelectrode in a microsystem comprising a Pt counter and a Ag/AgCl reference electrode. The functionalized microsystem was successfully applied for the sensing of dopamine with a detection limit of 50nM. Additionally, the microsystem exhibited good performance for the detection of dopamine levels in meat samples.

N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.

APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.

Enhanced DR5 binding capacity of nanovectorized TRAIL compared to its cytotoxic version by affinity chromatography and molecular docking studies.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of cancer cells when bound to its cognate receptors, TRAIL-R1 and TRAIL-R2 (DR4 and DR5), without being toxic to healthy cells. Nanovectorized TRAIL (abbreviated as NPT) is 10 to 20 times more efficient than one of the most potent soluble TRAIL used in preclinical studies (His-TRAIL). To determine whether differences in affinity may account for NPT superiority, a thermodynamic study was undertaken to evaluate NPT versus TRAIL binding affinity to DR5. Docking calculations showed that TRAIL in homotrimer configuration was more stable than in heterotrimer, because of the presence of one Zn ion in its structure. Indeed, TRAIL trimers can have head-to-tail orientations when Zn is missing. Altogether these data suggest that TRAIL homotrimer structures are predominant in solution and then are grafted on NPT. When docked to DR5, NPT carrying TRAIL homotrimer leads to a more stable complex than TRAIL monomer-based NPT. To comfort these observations, the extracellular domain of DR5 was immobilized on a chromatographic support using an "in situ" immobilization technique. The determination of the thermodynamic data (enthalpy ∆H° and entropy ∆S°*) of TRAIL and NPT binding to DR5 showed that the binding mechanism was pH dependent. The affinity of NPT to DR5 increased with pH, and the ionized energy was more important for NPT than for soluble TRAIL. Moreover, because of negative values of ∆H° and ∆S°* quantities, we demonstrated that van der Waals and hydrogen bonds governed the strong NPT-DR5 association for pH > 7.4 (as for TRAIL alone). Copyright © 2016 John Wiley & Sons, Ltd.

Nanovectorization of TRAIL with single wall carbon nanotubes enhances tumor cell killing.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily. This type II transmembrane protein is able to bound specifically to cancer cell receptors (i.e., TRAIL-R1 (or DR4) and TRAIL-R2 (or DR5)) and to induce apoptosis without being toxic for healthy cells. Because membrane-bound TRAIL induces stronger receptor aggregation and apoptosis than soluble TRAIL, we proposed here to vectorize TRAIL using single-walled carbon nanotubes (SWCNTs) to mimic membrane TRAIL. Owing to their exceptional and revolutional properties, carbon nanotubes, especially SWCNTs, are used in a wide range of physical or, now, medical applications. Indeed due to their high mechanical resistance, their high flexibility and their hydrophobicity, SWCNTs are known to rapidly diffuse in an aqueous medium such as blood, opening the way of development of new drug nanovectors (or nanocarriers). Our TRAIL-based SWCNTs nanovectors proved to be more efficient than TRAIL alone death receptors in triggering cancer cell killing. These NPTs increased TRAIL pro-apoptotic potential by nearly 20-fold in different Human tumor cell lines including colorectal, nonsmall cell lung cancer, or hepatocarcinomas. We provide thus a proof-of-concept that TRAIL nanovector derivatives based on SWCNT may be useful to future nanomedicine therapies.

Simple method for detection of extremely diluted anti beta-casein antibodies from glass bead based receptors.

The current work describes the elaboration of a simple, sensitive and reliable ß-casein modified glass beads, for the detection and quantification of its specific antibody anti ß-casein. This is an elementary receptor without electronic part, developed by grafting glass bead surface with the antigenic ß-casein via 3-aminopropyltriethoxy silane and then glutaraldehyde as cross-linker. The whole is realized by a classical process, called in two steps and in mild conditions where chemical protocol is optimized for ß-casein use. The detection and quantification of the specific reaction antibody-receptor is carried out by the technique of the second antibody labeled with horse radish peroxidase (HRP). Our receptor can detect the ß-casein antibody present in the serum at dilutions up to a factor 10(7) in strong ionic strength medium. The same antibody of the same serum and in the same conditions can be detected by ELISA test at dilutions up to a factor 10(5). The whole test, after our receptor realization, takes about 5h.

A new arginase enzymatic reactor: development and application for the research of plant-derived inhibitors.

This work was dedicated to the development of a new micro immobilized enzyme reactor (IMER) by using an in situ procedure. Arginase was covalently immobilized on an ethylenediamine (EDA) monolithic convective interaction media (CIM) disk (12mm × 3mm i.d.) previously derivatized with glutaraldehyde. The activity of this IMER was investigated by inserting this micro-IMER in a HPLC system. The effect of the arginase inhibitors was evaluated by the simultaneous injection of each inhibitor with the nitro guanidino benzene (NGB) substrate. The relative IC50 values were found in agreement with those derived by the conventional spectrometric method. This arginase micro-IMER system was also used to study the effects of plant-derived products on the arginase activity. The pet ether extract from the stem bark of the plant Ficus glomerata Roxob. and the procyanidin oligomers of cocoa and chocolate inhibit the arginase activity. Our results confirmed the direct effect of some plant extracts on the arginase activity and their interest in therapies for treating several NO-dependent smooth disorders.

Experimental studies of OH° radical/pressure dependence of arginase activity using a molecular chromatography approach.

Arginase is an enzyme which plays a role in pathophysiology such as hypertension. Here we demonstrated for the first time the direct implication of pressure and OH° radical formation on the arginase activity via a novel analytical procedure. Pressure increased arginase activity in the range 12-52bars. Activation by OH° radical showed a hyperbolic response. The OH° radicals produced were significantly inhibited by sulfasalazine (SAZ) and the inhibition of OH° radicals parallels the inhibition of arginase activity.

One-pot electrosynthesis of polyglycine-like thin film on platinum electrodes as transducer for solid state pH measurements.

The anodic oxidation of concentrated glycine based aqueous electrolyte on smooth platinum electrode leads to a strongly grafted polyglycine-like coating on the surface in an irreversible way. Due to the proton affinity towards amino groups of polyglycine (PG), the electrodeposited thin film was used as receptor for solid potentiometric pH sensor. In order to reach local pH measurement, we developed miniaturized microelectrodes on glass substrate thanks to photolithography process. We used silver chloride on silver as the reference electrode. The couple (silver chloride, PG based platinum electrode) of microelectrodes gives linear potentiometric response vs. pH in the range [2-12], reversibly and with a sensitivity of 52.4 mV/pH (for 1mm electrode size). PG based pH electrode is compared to other organic polymer based pH receptor such as linear polyethylenimine (L-PEI), polyaniline (PANI) and glass membrane.

Development of miniaturized pH biosensors based on electrosynthesized polymer films.

A new type of pH biosensor was developed for biological applications. This biosensor was fabricated using silicon microsystem technology and consists in two platinum microelectrodes. The first microelectrode was coated by an electrosynthesized polymer and acted as the pH sensitive electrode when the second one was coated by a silver layer and was used as the reference electrode. Then, this potentiometric pH miniaturized biosensor based on electrosynthesized polypyrrole or electrosynthesized linear polyethylenimine films was tested. The potentiometric responses appeared reversible and linear to pH changes in the range from pH 4 to 9. More, the responses were fast (less than 1 min for all sensors), they were stable in time since PPy/PEI films were stable during more than 30 days, and no interference was observed. The influence of the polymer thickness was also studied.