Size, polyglycerol grafting, and net surface charge of iron oxide nanoparticles determine their interaction and toxicity in Caenorhabditis elegans.

The widespread application of engineered nanoparticles (NPs) in environmental remediation has raised public concerns about their toxicity to aquatic organisms. Although appropriate surface modification can mitigate the ecotoxicity of NPs, the lack of polymer coating to inhibit toxicity completely and the insufficient knowledge about charge effect hinder the development of safe nanomaterials. Herein, we explored the potential of polyglycerol (PG) functionalization in alleviating the environmental risks of NPs. Iron oxide NPs (ION) of 20, 100, and 200 nm sizes (IONS, IONM and IONL, respectively) were grafted with PG to afford ION-PG. We examined the interaction of ION and ION-PG with Caenorhabditis elegans (C. elegans) and found that PG suppressed non-specific interaction of ION with C. elegans to reduce their accumulation and to inhibit their translocation. Particularly, IONS-PG was completely excluded from worms of all developmental stages. By covalently introducing sulfate, carboxyl and amino groups onto IONS-PG, we further demonstrated that positively charged IONS-PG-NH3+ induced high intestinal accumulation, cuticle adhesion and distal translocation, whereas the negatively charged IONS-PG-OSO3- and IONS-PG-COO- were excreted out. Consequently, no apparent deleterious effects on brood size and life span were observed in worms treated by IONS-PG and IONS-PG bearing negatively charged groups. This study presents new surface functionalization approaches for developing ecofriendly nanomaterials.

A magnetically responsive photonic crystal of graphene oxide nanosheets.

Magnetically responsive photonic crystals of colloidal nanosheets hold great promise for various applications. Here, we systematically investigated the magnetically responsive behavior of a photonic crystal consisting of graphene oxide (GO) nanosheets and water. After applying a 12 T magnetic field perpendicular and parallel to the observation direction, the photonic crystal exhibited a more vivid structural color and no structural color, respectively, based on the magnetic orientation of GO nanosheets. The reflection wavelength can be modulated by varying the GO concentration, and the peak intensity can be basically enhanced by increasing both the time and strength of the magnetic application. To improve color quality, we developed a novel approach of alternately applying a magnetic field to two orthogonal directions, instead of using a rotating magnetic field. Finally, we achieved color switching by changing the direction of applied magnetic fields.

Efficient and stable visible-light-driven Z-scheme overall water splitting using an oxysulfide H2 evolution photocatalyst.

So-called Z-scheme systems permit overall water splitting using narrow-bandgap photocatalysts. To boost the performance of such systems, it is necessary to enhance the intrinsic activities of the hydrogen evolution photocatalyst and oxygen evolution photocatalyst, promote electron transfer from the oxygen evolution photocatalyst to the hydrogen evolution photocatalyst, and suppress back reactions. The present work develop a high-performance oxysulfide photocatalyst, Sm2Ti2O5S2, as an hydrogen evolution photocatalyst for use in a Z-scheme overall water splitting system in combination with BiVO4 as the oxygen evolution photocatalyst and reduced graphene oxide as the solid-state electron mediator. After surface modifications of the photocatalysts to promote charge separation and redox reactions, this system is able to split water into hydrogen and oxygen for more than 100 hours with a solar-to-hydrogen energy conversion efficiency of 0.22%. In contrast to many existing photocatalytic systems, the water splitting activity of the present system is only minimally reduced by increasing the background pressure to 90 kPa. These results suggest characteristics suitable for applications under practical operating conditions.

Highly Stretchable Stress-Strain Sensor from Elastomer Nanocomposites with Movable Cross-links and Ketjenblack.

Practical applications like very thin stress-strain sensors require high strength, stretchability, and conductivity, simultaneously. One of the approaches is improving the toughness of the stress-strain sensing materials. Polymeric materials with movable cross-links in which the polymer chain penetrates the cavity of cyclodextrin (CD) demonstrate enhanced strength and stretchability, simultaneously. We designed two approaches that utilize elastomer nanocomposites with movable cross-links and carbon filler (ketjenblack, KB). One approach is mixing SC (a single movable cross-network material), a linear polymer (poly(ethyl acrylate), PEA), and KB to obtain their composite. The electrical resistance increases proportionally with tensile strain, leading to the application of this composite as a stress-strain sensor. The responses of this material are stable for over 100 loading and unloading cycles. The other approach is a composite made with KB and a movable cross-network elastomer for knitting dissimilar polymers (KP), where movable cross-links connect the CD-modified polystyrene (PSCD) and PEA. The obtained composite acts as a highly sensitive stress-strain sensor that exhibits an exponential increase in resistance with increasing tensile strain due to the polymer dethreading from the CD rings. The designed preparations of highly repeatable or highly responsive stress-strain sensors with good mechanical properties can help broaden their application in electrical devices.

Countercation Engineering of Graphene-Oxide Nanosheets for Imparting a Thermoresponsive Ability.

Graphene-oxide (GO) nanosheets, which are oxidized derivatives of graphene, are regarded as promising building blocks for functional soft materials. Especially, thermoresponsive GO nanosheets have been widely employed to develop smart membranes/surfaces, hydrogel actuators, recyclable systems, and biomedical applications. However, current synthetic strategies to generate such thermoresponsive GO nanosheets have exclusively relied on the covalent or non-covalent modification of their surfaces with thermoresponsive polymers, such as poly(N-isopropylacrylamide). To impart a thermoresponsive ability to GO nanosheets themselves, we focused on the countercations of the carboxy and acidic hydroxy groups on the GO nanosheets. In this study, we established a general and reliable method to synthesize GO nanosheets with target countercations and systematically investigated their effects on thermoresponsive behaviors of GO nanosheets. As a result, we discovered that GO nanosheets with Bu4N+ countercations became thermoresponsive in water without the use of any thermoresponsive polymers, inducing a reversible sol-gel transition via their self-assembly and disassembly processes. Owing to the sol-gel transition capability, the resultant dispersion can be used as a direct writing ink for constructing a three-dimensionally designable gel architecture of the GO nanosheets. Our concept of "countercation engineering" can become a new strategy for imparting a stimuli-responsive ability to various charged nanomaterials for the development of next-generation smart materials.

Polymyxin B complexation enhances the antimicrobial potential of graphene oxide.

Introduction: The antibacterial activity of graphene oxide (GO) has been widely explored and tested against various pathogenic bacterial strains. Although antimicrobial activity of GO against planktonic bacterial cells was demonstrated, its bacteriostatic and bactericidal effect alone is not sufficient to damage sedentary and well protected bacterial cells inside biofilms. Thus, to be utilized as an effective antibacterial agent, it is necessary to improve the antibacterial activity of GO either by integration with other nanomaterials or by attachment of antimicrobial agents. In this study, antimicrobial peptide polymyxin B (PMB) was adsorbed onto the surface of pristine GO and GO functionalized with triethylene glycol. Methods: The antibacterial effects of the resulting materials were examined by evaluating minimum inhibitory concentration, minimum bactericidal concentration, time kill assay, live/dead viability staining and scanning electron microscopy. Results and discussion: PMB adsorption significantly enhanced the bacteriostatic and bactericidal activity of GO against both planktonic cells and bacterial cells in biofilms. Furthermore, the coatings of PMB-adsorbed GO applied to catheter tubes strongly mitigated biofilm formation, by preventing bacterial adhesion and killing the bacterial cells that managed to attach. The presented results suggest that antibacterial peptide absorption can significantly enhance the antibacterial activity of GO and the resulting material can be effectively used not only against planktonic bacteria but also against infectious biofilms.

Unveiling the Reduction Process of Graphene Oxide by Ascorbic Acid: Grafting and Reduction Sequences for High Surface Area Graphene Materials.

This work reports the synthesis of high surface area reduced graphene oxides using L-ascorbic acid as a reducing agent by precisely controlling the interaction between graphene oxide and L-ascorbic acid. Based on the structural characterization, such as textural properties (specific surface area, pore structure), crystallinity, and carbon chemical state, we identified that the temperature and reaction time are critical parameters to control the stacking degree of the final reduced product. Besides, by performing a time course analysis of the reaction, we identified the side products of the reducing agent by LC-MS and verified the reduction mechanism. Following our results, we proposed an optimum condition for producing a graphene derivative adsorbent with a high surface area. This graphene derivative was tested in an aqueous solution with organic and inorganic pollutants such as methylene blue, methyl orange, and cadmium.

Correction to "Bonding of Neuropeptide Y on Graphene Oxide for Drug Delivery Applications to the Central Nervous System".

[This corrects the article DOI: 10.1021/acsanm.2c03409.].

Angstrom-Confined Electrochemical Synthesis of Sub-Unit-Cell Non-Van Der Waals 2D Metal Oxides.

Bottom-up electrochemical synthesis of atomically thin materials is desirable yet challenging, especially for non-van der Waals (non-vdW) materials. Thicknesses below a few nanometers have not been reported yet, posing the question how thin can non-vdW materials be electrochemically synthesized. This is important as materials with (sub-)unit-cell thickness often show remarkably different properties compared to their bulk form or thin films of several nanometers thickness. Here, a straightforward electrochemical method utilizing the angstrom-confinement of laminar reduced graphene oxide (rGO) nanochannels is introduced to obtain a centimeter-scale network of atomically thin (<4.3 Å) 2D-transition metal oxides (2D-TMO). The angstrom-confinement provides a thickness limitation, forcing sub-unit-cell growth of 2D-TMO with oxygen and metal vacancies. It is showcased that Cr2 O3 , a material without significant catalytic activity for the oxygen evolution reaction (OER) in bulk form, can be activated as a high-performing catalyst if synthesized in the 2D sub-unit-cell form. This method displays the high activity of sub-unit-cell form while retaining the stability of bulk form, promising to yield unexplored fundamental science and applications. It is shown that while retaining the advantages of bottom-up electrochemical synthesis, like simplicity, high yield, and mild conditions, the thickness of TMO can be limited to sub-unit-cell dimensions.

Edge-Site-Free and Topological-Defect-Rich Carbon Cathode for High-Performance Lithium-Oxygen Batteries.

The rational design of a stable and catalytic carbon cathode is crucial for the development of rechargeable lithium-oxygen (LiO2 ) batteries. An edge-site-free and topological-defect-rich graphene-based material is proposed as a pure carbon cathode that drastically improves LiO2 battery performance, even in the absence of extra catalysts and mediators. The proposed graphene-based material is synthesized using the advanced template technique coupled with high-temperature annealing at 1800 °C. The material possesses an edge-site-free framework and mesoporosity, which is crucial to achieve excellent electrochemical stability and an ultra-large capacity (>6700 mAh g-1 ). Moreover, both experimental and theoretical structural characterization demonstrates the presence of a significant number of topological defects, which are non-hexagonal carbon rings in the graphene framework. In situ isotopic electrochemical mass spectrometry and theoretical calculations reveal the unique catalysis of topological defects in the formation of amorphous Li2 O2 , which may be decomposed at low potential (∼ 3.6 V versus Li/Li+ ) and leads to improved cycle performance. Furthermore, a flexible electrode sheet that excludes organic binders exhibits an extremely long lifetime of up to 307 cycles (>1535 h), in the absence of solid or soluble catalysts. These findings may be used to design robust carbon cathodes for LiO2 batteries.

Real-World Experience of the Comparative Effectiveness and Safety of Molnupiravir and Nirmatrelvir/Ritonavir in High-Risk Patients with COVID-19 in a Community Setting.

Molnupiravir (MOV) and nirmatrelvir/ritonavir (NMV/r) are efficacious oral antiviral agents for patients with the 2019 coronavirus (COVID-19). However, little is known about their effectiveness in older adults and those at high risk of disease progression. This retrospective single-center observational study assessed and compared the outcomes of COVID-19 treated with MOV and NMV/r in a real-world community setting. We included patients with confirmed COVID-19 combined with one or more risk factors for disease progression from June to October 2022. Of 283 patients, 79.9% received MOV and 20.1% NMV/r. The mean patient age was 71.7 years, 56.5% were men, and 71.7% had received ≥3 doses of vaccine. COVID-19-related hospitalization (2.8% and 3.5%, respectively; p = 0.978) or death (0.4% and 3.5%, respectively; p = 0.104) did not differ significantly between the MOV and NMV/r groups. The incidence of adverse events was 2.7% and 5.3%, and the incidence of treatment discontinuation was 2.7% and 5.3% in the MOV and NMV/r groups, respectively. The real-world effectiveness of MOV and NMV/r was similar among older adults and those at high risk of disease progression. The incidence of hospitalization or death was low.

Graphene Oxide-BODIPY Conjugates as Highly Fluorescent Materials.

Covalent functionalization of graphene oxide (GO) with boron dipyrromethenes (BODIPYs) was achieved through a facile synthesis, affording two different GO-BODIPY conjugates where the main difference lies in the nature of the spacer and the type of bonds between the two components. The use of a long but flexible spacer afforded strong electronic GO-BODIPY interactions in the ground state. This drastically altered the light absorption of the BODIPY structure and impeded its selective excitation. In contrast, the utilisation of a short, but rigid spacer based on boronic esters resulted in a perpendicular geometry of the phenyl boronic acid BODIPY (PBA-BODIPY) with respect to the GO plane, which enables only minor electronic GO-BODIPY interactions in the ground state. In this case, selective excitation of PBA-BODIPY was easily achieved, allowing to investigate the excited state interactions. A quantitative ultrafast energy transfer from PBA-BODIPY to GO was observed. Furthermore, due to the reversible dynamic nature of the covalent GO-PBA-BODIPY linkage, some PBA-BODIPY is free in solution and, hence, not quenched from GO. This resulted in a weak, but detectable fluorescence from the PBA-BODIPY that will allow to exploit GO-PBA-BODIPY for slow release and imaging purposes.

Non-enzymatic detection of glucose levels in human blood plasma by a graphene oxide-modified organic transistor sensor.

We herein report an organic transistor functionalized with a phenylboronic acid derivative and graphene oxide for the quantification of plasma glucose levels, which has been achieved by the minimization of interferent effects derived from physical protein adsorption on the detection electrode.

Functional Graphene for Peritumoral Brain Microenvironment Modulation Therapy in Glioblastoma.

Peritumoral brain invasion is the main target to cure glioblastoma. Chemoradiotherapy and targeted therapies fail to combat peritumoral relapse. Brain inaccessibility and tumor heterogeneity explain this failure, combined with overlooking the peritumor microenvironment. Reduce graphene oxide (rGO) provides a unique opportunity to modulate the local brain microenvironment. Multimodal graphene impacts are reported on glioblastoma cells in vitro but fail when translated in vivo because of low diffusion. This issue is solved by developing a new rGO formulation involving ultramixing during the functionalization with polyethyleneimine (PEI) leading to the formation of highly water-stable rGO-PEI. Wide mice brain diffusion and biocompatibility are demonstrated. Using an invasive GL261 model, an anti-invasive effect is observed. A major unexpected modification of the peritumoral area is also observed with the neutralization of gliosis. In vitro, mechanistic investigations are performed using primary astrocytes and cytokine array. The result suggests that direct contact of rGO-PEIUT neutralizes astrogliosis, decreasing several proinflammatory cytokines that would explain a bystander tumor anti-invasive effect. rGO also significantly downregulates several proinvasive/protumoral cytokines at the tumor cell level. The results open the way to a new microenvironment anti-invasive nanotherapy using a new graphene nanomaterial that is optimized for in vivo brain delivery.

Mechanisms of Radical Formation on Chemically Modified Graphene Oxide under Near Infrared Irradiation.

In this work, the mechanisms of radical generation on different functionalized graphene oxide (GO) conjugates under near-infrared (NIR) light irradiation are investigated. The GO conjugates are designed to understand how chemical functionalization can influence the generation of radicals. Both pristine and functionalized GO are irradiated by a NIR laser, and the production of different reactive oxygen species (ROS) is investigated using fluorimetry and electron paramagnetic resonance to describe the type of radicals present on the surface of GO. The mechanism of ROS formation involves a charge transfer from the material to the oxygen present in the media, via the production of superoxide and singlet oxygen. Cytotoxicity and effects of ROS generation are then evaluated using breast cancer cells, evidencing a concentration dependent cell death associated to the heat and ROS. The study provides new hints to understand the photogeneration of radicals on the surface of GO upon near infrared irradiation, as well as, to assess the impact on these radicals in the context of a combined drug delivery system and phototherapeutic approach. These discoveries open the way for a better control of phototherapy-based treatments employing graphene-based materials.

Plasma-Derived Fibrin Hydrogels Containing Graphene Oxide for Infections Treatment.

Wound infection is inevitable in most patients suffering from extensive burns or chronic ulcers, and there is an urgent demand for the production of bactericidal dressings to be used as grafts to restore skin functionalities. In this context, the present study explores the fabrication of plasma-derived fibrin hydrogels containing bactericidal hybrids based on graphene oxide (GO). The hydrogels were fully characterized regarding gelation kinetics, mechanical properties, and internal hydrogel structures by disruptive cryo scanning electron microscopies (cryo-SEMs). The gelation kinetic experiments revealed an acceleration of the gel formation when GO was added to the hydrogels in a concentration of up to 0.2 mg/mL. The cryo-SEM studies showed up a decrease of the pore size when GO was added to the network, which agreed with a faster area contraction and a higher compression modulus of the hydrogels that contained GO, pointing out the critical structural role of the nanomaterial. Afterward, to study the bactericidal ability of the gels, GO was used as a carrier, loading streptomycin (STREP) on its surface. The loading content of the drug to form the hybrid (GO/STREP) resulted in 50.2% ± 4.7%, and the presence of the antibiotic was also demonstrated by Raman spectroscopy, Z-potential studies, and thermogravimetric analyses. The fibrin-derived hydrogels containing GO/STREP showed a dose-response behavior according to the bactericidal hybrid concentration and allowed a sustained release of the antibiotic at a programmed rate, leading to drug delivery over a prolonged period of time.

Bonding of Neuropeptide Y on Graphene Oxide for Drug Delivery Applications to the Central Nervous System.

Nanoscale graphene-based materials (GBMs) enable targeting subcellular structures of the nervous system, a feature crucial for the successful engineering of alternative nanocarriers to deliver drugs and to treat neurodisorders. Among GBMs, graphene oxide (GO) nanoflakes, showing good dispersibility in water solution and being rich of functionalizable oxygen groups, are ideal core structures for carrying biological active molecules to the brain, such as the neuropeptide Y (NPY). In addition, when unconjugated, these nanomaterials have been reported to modulate neuronal function per se. Although some GBM-based nanocarriers have been tested both in vitro and in vivo, a thorough characterization of covalent binding impact on the biological properties of the carried molecule and/or of the nanomaterial is still missing. Here, a copper(I)-catalyzed alkyne-azide cycloaddition strategy was employed to synthesize the GO-NPY complex. By investigating through electrophysiology the impact of these conjugates on the activity of hippocampal neurons, we show that the covalent modification of the nanomaterial, while making GO an inert platform for the vectorized delivery, enhances the duration of NPY pharmacological activity. These findings support the future use of GO for the development of smart platforms for nervous system drug delivery.

Graphene Oxide-based Endodontic Sealer: An in Vitro Study.

The failure of endodontic treatment is directly associated with microbial infection in the root canal or periapical areas. An endodontic sealer that is both bactericidal and biocompatible is essential for the success of root canal treatments. This is one of the vital issues yet to be solved in clinical dental practice. This in vitro study assessed the effectiveness of graphene oxide (GO) composites GO-CaF2 and GO-Ag-CaF2 as endodontic sealer materials. Dentin slices were coated with either the GO-based composites or commonly used root canal sealers (non-eugenol zinc oxide sealer). The coated slices were treated in 0.9% NaCl, phosphate-buffered saline (PBS), and simulated body fluid (SBF) at 37˚C for 24 hours to compare their sealing effect on the dentin surface. In addition, the radiopacity of these composites was examined to assess whether they complied with the requirements of a sealer for good radiographic visualization. Scanning electron microscopy showed the significant sealing capability of the composites as coating materials. Radiographic images confirmed their radiopacity. Mineral deposition indicated their bioactivity, especially of GO-Ag-CaF2, and thus it is potential for regenerative application. They were both previously shown to be bactericidal to oral microbes and cytocompatible with host cells. With such a unique assemblage of critical properties, these GO-based composites show promise as endodontic sealers for protection against reinfection in root canal treatment and enhanced success in endodontic treatment overall.

Room-Temperature Ring-Opening Polymerization of δ-Valerolactone and ϵ-Caprolactone Caused by Uptake into Porous Pillar[5]arene Crystals.

Confined space provides a reaction platform with altered reaction rate and selectivity compared with a homogeneous solution. In this work, porous phenolic pillar[5]arene crystals were used as a reaction space to promote and perturb equilibrium between lactones and their corresponding polyesters. Immersion of porous pillar[5]arene crystals in liquid lactones induced ring-opening polymerization of δ-valerolactone and ϵ-caprolactone at room temperature because the phenolic hydroxy groups have catalytic activity via hydrogen bonds and the pillar[5]arene cavities prefer linear guests. After the reaction, pillar[5]arene and polyesters formed pseudo-polyrotaxanes.