Protein‐Corona‐by‐Design in 2D: A Reliable Platform to Decode Bio–Nano Interactions for the Next‐Generation Quality‐by‐Design Nanomedicines

Hard corona (HC) protein, i.e., the environmental proteins of the biological medium that are bound to a nanosurface, is known to affect the biological fate of a nanomedicine. Due to the size, curvature, and specific surface area (SSA) 3‐factor interactions inherited in the traditional 3D nanoparticle, HC‐dependent bio–nano interactions are often poorly probed and interpreted. Here, the first HC‐by‐design case study in 2D is demonstrated that sequentially and linearly changes the HC quantity using functionalized graphene oxide (GO) nanosheets. The HC quantity and HC quality are analyzed using NanoDrop and label‐free liquid chromatography–mass spectrometry (LC‐MS) followed by principal component analysis (PCA). Cellular responses (uptake and cytotoxicity in J774 cell model) are compared using imaging cytometry and the modified lactate dehydrogenase assays, respectively. Cellular uptake linearly and solely correlates with HC quantity (R² = 0.99634). The nanotoxicity, analyzed by retrospective design of experiment (DoE), is found to be dependent on the nanomaterial uptake (primary), HC composition (secondary), and nanomaterial exposure dose (tertiary). This unique 2D design eliminates the size–curvature–SSA multifactor interactions and can serve as a reliable screening platform to uncover HC‐dependent bio–nano interactions to enable the next‐generation quality‐by‐design (QbD) nanomedicines for better clinical translation.     

Mass Cytometry and Single‐Cell RNA‐seq Profiling of the Heterogeneity in Human Peripheral Blood Mononuclear Cells Interacting with Silver Nanoparticles

Understanding the interactions between nanoparticles (NPs) and human immune cells is necessary for justifying their utilization in consumer products and biomedical applications. However, conventional assays may be insufficient in describing the complexity and heterogeneity of cell–NP interactions. Herein, mass cytometry and single‐cell RNA‐sequencing (scRNA‐seq) are complementarily used to investigate the heterogeneous interactions between silver nanoparticles (AgNPs) and primary immune cells. Mass cytometry reveals the heterogeneous biodistribution of the positively charged polyethylenimine‐coated AgNPs in various cell types and finds that monocytes and B cells have higher association with the AgNPs than other populations. scRNA‐seq data of these two cell types demonstrate that each type has distinct responses to AgNP treatment: NRF2‐mediated oxidative stress is confined to B cells, whereas monocytes show Fcγ‐mediated phagocytosis. Besides the between‐population heterogeneity, analysis of single‐cell dose–response relationships further reveals within‐population diversity for the B cells and naïve CD4⁺ T cells. Distinct subsets having different levels of cellular responses with respect to their cellular AgNP doses are found. This study demonstrates that the complementary use of mass cytometry and scRNA‐seq is helpful for gaining in‐depth knowledge on the heterogeneous interactions between immune cells and NPs and can be incorporated into future toxicity assessments of nanomaterials.     

Gating of Single‐Layer Graphene with Single‐Stranded Deoxyribonucleic Acids

Patterning of biomolecules on graphene layers could provide new avenues to modulate their electrical properties for novel electronic devices. Single‐stranded deoxyribonucleic acids (ssDNAs) are found to act as negative‐potential gating agents that increase the hole density in single‐layer graphene. Current–voltage measurements of the hybrid ssDNA/graphene system indicate a shift in the Dirac point and “intrinsic” conductance after ssDNA is patterned. The effect of ssDNA is to increase the hole density in the graphene layer, which is calculated to be on the order of 1.8 × 10¹² cm^?2. This increased density is consistent with the Raman frequency shifts in the G‐peak and 2D band positions and the corresponding changes in the G‐peak full width at half maximum. Ab initio calculations using density functional theory rule out significant charge transfer or modification of the graphene band structure in the presence of ssDNA fragments.     

Graphene Oxide Sieving Membrane for Improved Cycle Life in High‐Efficiency Redox‐Mediated Li–O2 batteries

As soluble catalysts, redox‐mediators (RMs) endow mobility to catalysts for unconstrained access to tethered solid discharge products, lowering the energy barrier for Li₂O₂ formation/decomposition; however, this desired mobility is accompanied by the undesirable side effect of RM migration to the Li metal anode. The reaction between RMs and Li metal degrades both the Li metal and the RMs, leading to cell deterioration within a few cycles. To extend the cycle life of redox‐mediated Li–O₂ batteries, herein graphene oxide (GO) membranes are reported as RM‐blocking separators. It is revealed that the size of GO nanochannels is narrow enough to reject 5,10‐dihydro‐5,10‐dimethylphenazine (DMPZ) while selectively allowing the transport of smaller Li⁺ ions. The negative surface charges of GO further repel negative ions via Donnan exclusion, greatly improving the lithium ion transference number. The Li–O₂ cells with GO membranes efficiently harness the redox‐mediation activity of DMPZ for improved performance, achieving energy efficiency of above 80% for more than 25 cycles, and 90% for 78 cycles when the capacity limits were 0.75 and 0.5 mAh cm^‐2, respectively. Considering the facile preparation of GO membranes, RM‐sieving GO membranes can be cost‐effective and processable functional separators in Li–O₂ batteries.     

Intracellular Imaging with a Graphene‐Based Fluorescent Probe

Graphene is an increasingly important nanomaterial that has shown great promise in the area of nanotechnology. In this study, fluorescein‐functionalized graphene oxide (GO) is synthesized via a polyethylene glycol (PEG) bridge and its application in intracellular imaging is explored. GO is an oxide form of graphene that provides an ideal platform to prepare graphene‐based functional nanomaterials via chemical modification. The PEG bridge was introduced to prevent GO‐induced quenching of conjugated fluorescein. The fluorescein–PEG–GO conjugate thus prepared exhibits excellent pH‐tunable fluorescent properties and, more significantly, can be efficiently taken up by cells and serve as a fluorescent nanoprobe for intracellular imaging.     

Mechanistic Differences in Cell Death Responses to Metal‐Based Engineered Nanomaterials in Kupffer Cells and Hepatocytes

The mononuclear phagocyte system in the liver is a frequent target for nanoparticles (NPs). A toxicological profiling of metal‐based NPs is performed in Kupffer cell (KC) and hepatocyte cell lines. Sixteen NPs are provided by the Nanomaterial Health Implications Research Consortium of the National Institute of Environmental Health Sciences to study the toxicological effects in KUP5 (KC) and Hepa 1–6 cells. Five NPs (Ag, CuO, ZnO, SiO₂, and V₂O₅) exhibit cytotoxicity in both cell types, while SiO₂ and V₂O₅ induce IL‐1β production in KC. Ag, CuO, and ZnO induced caspase 3 generated apoptosis in both cell types is accompanied by ion shedding and generation of mitochondrial reactive oxygen species (ROS) in both cell types. However, the cell death response to SiO₂ in KC differs by inducing pyroptosis as a result of potassium efflux, caspase 1 activation, NLRP3 inflammasome assembly, IL‐1β release, and cleavage of gasdermin‐D. This releases pore‐performing peptide fragments responsible for pyroptotic cell swelling. Interestingly, although V₂O₅ induces IL‐1β release and delays caspase 1 activation by vanadium ion interference in membrane Na⁺/K⁺ adenosine triphosphate (ATP)ase activity, the major cell death mechanism in KC (and Hepa 1–6) is caspase 3 mediated apoptosis. These findings improve the understanding of the mechanisms of metal‐based engineered nanomaterial (ENM) toxicity in liver cells toward comprehensive safety evaluation.     

Single‐ and Double‐Sided Chemical Functionalization of Bilayer Graphene

An experimental study on the interaction between the top and bottom layer of a chemically functionalized graphene bilayer by mild oxygen plasma is reported. Structural, chemical, and electrical properties are monitored using Raman spectroscopy, transport measurements, conductive atomic force microscopy and X‐ray photoelectron spectroscopy. Single‐ and double‐sided chemical functionalization are found to give very different results: single‐sided modified bilayers show relatively high mobility (200–600 cm² V^?1 s^?1 at room temperature) and a stable structure with a limited amount of defects, even after long plasma treatment (>60 s). This is attributed to preferential modification and limited coverage of the top layer during plasma exposure, while the bottom layer remains almost unperturbed. This could eventually lead to decoupling between top and bottom layers. Double‐sided chemical functionalization leads to a structure containing a high concentration of defects, very similar to graphene oxide. This opens the possibility to use plasma treatment not only for etching and patterning of graphene, but also to make heterostructures (through single‐sided modification of bilayers) for sensors and transistors and new graphene‐derivatives materials (through double‐sided modification).     

Extrusion‐Based 3D Printing of Hierarchically Porous Advanced Battery Electrodes

A highly porous 2D nanomaterial, holey graphene oxide (hGO), is synthesized directly from holey graphene powder and employed to create an aqueous 3D printable ink without the use of additives or binders. Stable dispersions of hydrophilic hGO sheets in water (≈100 mg mL^?1) can be readily achieved. The shear‐thinning behavior of the aqueous hGO ink enables extrusion‐based printing of fine filaments into complex 3D architectures, such as stacked mesh structures, on arbitrary substrates. The freestanding 3D printed hGO meshes exhibit trimodal porosity: nanoscale (4–25 nm through‐holes on hGO sheets), microscale (tens of micrometer‐sized pores introduced by lyophilization), and macroscale (<500 µm square pores of the mesh design), which are advantageous for high‐performance energy storage devices that rely on interfacial reactions to promote full active‐site utilization. To elucidate the benefit of (nano)porosity and structurally conscious designs, the additive‐free architectures are demonstrated as the first 3D printed lithium–oxygen (Li–O₂) cathodes and characterized alongside 3D printed GO‐based materials without nanoporosity as well as nanoporous 2D vacuum filtrated films. The results indicate the synergistic effect between 2D nanomaterials, hierarchical porosity, and overall structural design, as well as the promise of a freeform generation of high‐energy‐density battery systems.     

A Chiral‐Nanoassemblies‐Enabled Strategy for Simultaneously Profiling Surface Glycoprotein and MicroRNA in Living Cells

Assemblies of nanomaterials for biological applications in living cells have attracted much attention. Herein, graphene oxide (GO)–gold nanoparticle (Au NP) assemblies are driven by a splint DNA strand, which is designed with two regions at both ends that are complementary with the DNA sequence anchored on the surface of the GO and the Au NPs. In the presence of microRNA (miR)‐21 and epithelial cell‐adhesion molecule (EpCAM), the hybridization of miR‐21 with a molecular probe leads to the separation of 6‐fluorescein‐phosphoramidite‐modified Au NPs from GO, resulting in a decrease in the Raman signal, while EpCAM recognition reduces circular dichroism (CD) signals. The CD signals reverse from negative in original assemblies into positive when reacted with cells, which correlates with two enantiomer geometries. The EpCAM detection has a good linear range of 8.47–74.78 pg mL^?1 and a limit of detection (LOD) of 3.63 pg mL^?1, whereas miR‐21 detection displays an outstanding linear range of 0.07–13.68 amol ng^?1_RNA and LOD of 0.03 amol ng^?1_RNA. All the results are in good agreement with those of the Raman and confocal bioimaging. The strategy opens up an avenue to allow the highly accurate and reliable diagnosis (dual targets) of clinic diseases.     

Number‐Resolved Single‐Photon Detection with Ultralow Noise van der Waals Hybrid

Van der Waals hybrids of graphene and transition metal dichalcogenides exhibit an extremely large response to optical excitation, yet counting of photons with single‐photon resolution is not achieved. Here, a dual‐gated bilayer graphene (BLG) and molybdenum disulphide (MoS₂) hybrid are demonstrated, where opening a band gap in the BLG allows extremely low channel (receiver) noise and large optical gain (≈10¹⁰) simultaneously. The resulting device is capable of unambiguous determination of the Poissonian emission statistics of an optical source with single‐photon resolution at an operating temperature of 80 K, dark count rate 0.07 Hz, and linear dynamic range of ≈40 dB. Single‐shot number‐resolved single‐photon detection with van der Waals heterostructures may impact multiple technologies, including the linear optical quantum computation.     

Graphene–Graphene Oxide Floating Gate Transistor Memory

A novel transparent, flexible, graphene channel floating‐gate transistor memory (FGTM) device is fabricated using a graphene oxide (GO) charge trapping layer on a plastic substrate. The GO layer, which bears ammonium groups (NH₃⁺), is prepared at the interface between the crosslinked PVP (cPVP) tunneling dielectric and the Al₂O₃ blocking dielectric layers. Important design rules are proposed for a high‐performance graphene memory device: i) precise doping of the graphene channel, and ii) chemical functionalization of the GO charge trapping layer. How to control memory characteristics by graphene doping is systematically explained, and the optimal conditions for the best performance of the memory devices are found. Note that precise control over the doping of the graphene channel maximizes the conductance difference at a zero gate voltage, which reduces the device power consumption. The proposed optimization via graphene doping can be applied to any graphene channel transistor‐type memory device. Additionally, the positively charged GO (GO–NH₃⁺) interacts electrostatically with hydroxyl groups of both UV‐treated Al₂O₃ and PVP layers, which enhances the interfacial adhesion, and thus the mechanical stability of the device during bending. The resulting graphene–graphene oxide FGTMs exhibit excellent memory characteristics, including a large memory window (11.7 V), fast switching speed (1 μs), cyclic endurance (200 cycles), stable retention (10⁵ s), and good mechanical stability (1000 cycles).     

Heterogeneous Single‐Atom Catalyst for Visible‐Light‐Driven High‐Turnover CO2 Reduction: The Role of Electron Transfer

Visible‐light‐driven conversion of CO₂ into chemical fuels is an intriguing approach to address the energy and environmental challenges. In principle, light harvesting and catalytic reactions can be both optimized by combining the merits of homogeneous and heterogeneous photocatalysts; however, the efficiency of charge transfer between light absorbers and catalytic sites is often too low to limit the overall photocatalytic performance. In this communication, it is reported that the single‐atom Co sites coordinated on the partially oxidized graphene nanosheets can serve as a highly active and durable heterogeneous catalyst for CO₂ conversion, wherein the graphene bridges homogeneous light absorbers with single‐atom catalytic sites for the efficient transfer of photoexcited electrons. As a result, the turnover number for CO production reaches a high value of 678 with an unprecedented turnover frequency of 3.77 min^?1, superior to those obtained with the state‐of‐the‐art heterogeneous photocatalysts. This work provides fresh insights into the design of catalytic sites toward photocatalytic CO₂ conversion from the angle of single‐atom catalysis and highlights the role of charge kinetics in bridging the gap between heterogeneous and homogeneous photocatalysts.     

A Scalable Approach to Dendrite‐Free Lithium Anodes via Spontaneous Reduction of Spray‐Coated Graphene Oxide Layers

Li‐metal batteries (LiMBs) are experiencing a renaissance; however, achieving scalable production of dendrite‐free Li anodes for practical application is still a formidable challenge. Herein, a facile and universal method is developed to directly reduce graphene oxide (GO) using alkali metals (e.g., Li, Na, and K) in moderate conditions. Based on this innovation, a spontaneously reduced graphene coating can be designed and modulated on a Li surface (SR‐G‐Li). The symmetrical SR‐G‐Li|SR‐G‐Li cell can run up to 1000 cycles at a high practical current density of 5 mA cm^?2 without a short circuit, demonstrating one of the longest lifespans reported with LiPF₆‐based carbonate electrolytes. More significantly, a practically scalable paradigm is established to fabricate dendrite‐free Li anodes by spraying a GO layer on the Li anode surface for large‐scale production of LiFePO₄/Li pouch cells, reflected by the continuous manufacturing of the SR‐G‐Li anodes based on the roll‐to‐roll technology. The strategy provides new commercial opportunities to both LiMBs and graphene.     

Improved Biocompatibility of Amino‐Functionalized Graphene Oxide in Caenorhabditis elegans

Graphene oxide (GO) holds high promise for diagnostic and therapeutic applications in nanomedicine but reportedly displays immunotoxicity, underlining the need for developing functionalized GO with improved biocompatibility. This study describes adverse effects of GO and amino‐functionalized GO (GONH₂) during Caenorhabditis elegans development and ageing upon acute or chronic exposure. Chronic GO treatment throughout the C. elegans development causes decreased fecundity and a reduction of animal size, while acute treatment does not lead to any measurable physiological decline. However, RNA‐Sequencing data reveal that acute GO exposure induces innate immune gene expression. The p38 MAP kinase, PMK‐1, which is a well‐established master regulator of innate immunity, protects C. elegans from chronic GO toxicity, as pmk‐1 mutants show reduced tissue‐functionality and facultative vivipary. In a direct comparison, GONH₂ exposure does not cause detrimental effects in the wild type or in pmk‐1 mutants, and the innate immune response is considerably less pronounced. This work establishes enhanced biocompatibility of amino‐functionalized GO in a whole‐organism, emphasizing its potential as a biomedical nanomaterial.     

High Volumetric Energy Density Asymmetric Supercapacitors Based on Well‐Balanced Graphene and Graphene‐MnO2 Electrodes with Densely Stacked Architectures

The well‐matched electrochemical parameters of positive and negative electrodes, such as specific capacitance, rate performance, and cycling stability, are important for obtaining high‐performance asymmetric supercapacitors. Herein, a facile and cost‐effective strategy is demonstrated for the fabrication of 3D densely stacked graphene (DSG) and graphene‐MnO₂ (G‐MnO₂) architectures as the electrode materials for asymmetric supercapacitors (ASCs) by using MnO₂‐intercalated graphite oxide (GO‐MnO₂) as the precursor. DSG has a stacked graphene structure with continuous ion transport network in‐between the sheets, resulting in a high volumetric capacitance of 366 F cm^–3, almost 2.5 times than that of reduced graphene oxide, as well as long cycle life (93% capacitance retention after 10 000 cycles). More importantly, almost similar electrochemical properties, such as specific capacitance, rate performance, and cycling stability, are obtained for DSG as the negative electrode and G‐MnO₂ as the positive electrode. As a result, the assembled ASC delivers both ultrahigh gravimetric and volumetric energy densities of 62.4 Wh kg^–1 and 54.4 Wh L^–1 (based on total volume of two electrodes) in 1 m Na₂SO₄ aqueous electrolyte, respectively, much higher than most of previously reported ASCs in aqueous electrolytes.     

Electric Power Generation through the Direct Interaction of Pristine Graphene‐Oxide with Water Molecules

Converting ubiquitous environmental energy into electric power holds tremendous social and financial interests. Traditional energy harvesters and converters are limited by the specific materials and complex configuration of devices. Herein, it is presented that electric power can be directly produced from pristine graphene oxide (GO) without any pretreatment or additives once encountering the water vapor, which will generate an open‐circuit‐voltage of up to 0.4–0.7 V and a short‐circuit‐current‐density of 2–25 µA cm^?2 on a single piece of GO film. This phenomenon results from the directional movement of charged hydrogen ions through the GO film. The present work demonstrates and provides an extremely simple method for electric energy generation, which offers more applications of graphene‐based materials in green energy converting field.     

Mixed‐Valence Single‐Atom Catalyst Derived from Functionalized Graphene

Single‐atom catalysts (SACs) aim at bridging the gap between homogeneous and heterogeneous catalysis. The challenge is the development of materials with ligands enabling coordination of metal atoms in different valence states, and preventing leaching or nanoparticle formation. Graphene functionalized with nitrile groups (cyanographene) is herein employed for the robust coordination of Cu(II) ions, which are partially reduced to Cu(I) due to graphene‐induced charge transfer. Inspired by nature's selection of Cu(I) in enzymes for oxygen activation, this 2D mixed‐valence SAC performs flawlessly in two O₂‐mediated reactions: the oxidative coupling of amines and the oxidation of benzylic C? H bonds toward high‐value pharmaceutical synthons. High conversions (up to 98%), selectivities (up to 99%), and recyclability are attained with very low metal loadings in the reaction. The synergistic effect of Cu(II) and Cu(I) is the essential part in the reaction mechanism. The developed strategy opens the door to a broad portfolio of other SACs via their coordination to various functional groups of graphene, as demonstrated by successful entrapment of Fe^III/Fe^II single atoms to carboxy‐graphene.     

Reduced Graphene Oxide‐Wrapped Co9–xFexS8/Co,Fe‐N‐C Composite as Bifunctional Electrocatalyst for Oxygen Reduction and Evolution

Searching for highly efficient bifunctional electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) using nonnoble metal‐based catalysts is essential for the development of many energy conversion systems, including rechargeable fuel cells and metal–air batteries. Here, Co_9–xFe_xS₈/Co,Fe‐N‐C hybrids wrapped by reduced graphene oxide (rGO) (abbreviated as S‐Co_9–xFe_xS₈@rGO) are synthesized through a semivulcanization and calcination method using graphene oxide (GO) wrapped bimetallic zeolite imidazolate framework (ZIF) Co,Fe‐ZIF (CoFe‐ZIF@GO) as precursors. Benefiting from the synergistic effect of OER active CoFeS and ORR active Co,Fe‐N‐C in a single component, as well as high dispersity and enhanced conductivity derived from rGO coating and Fe‐doping, the obtained S‐Co_9–xFe_xS₈@rGO‐10 catalyst shows an ultrasmall overpotential of ≈0.29 V at 10 mA cm^?2 in OER and a half‐wave potential of 0.84 V in ORR, combining a superior oxygen electrode activity of ≈0.68 V in 0.1 m KOH.     

Fabrication of Millimeter‐Scale,Single‐Crystal One‐Third‐Hydrogenated Graphene with Anisotropic Electronic Properties

Periodically hydrogenated graphene is predicted to form new kinds of crystalline 2D materials such as graphane, graphone, and 2D C_xH_y, which exhibit unique electronic properties. Controlled synthesis of periodically hydrogenated graphene is needed for fundamental research and possible electronic applications. Only small patches of such materials have been grown so far, while the experimental fabrication of large‐scale, periodically hydrogenated graphene has remained challenging. In the present work, large‐scale, periodically hydrogenated graphene is fabricated on Ru(0001). The as‐fabricated hydrogenated graphene is highly ordered, with a √3 × √3/R30° period relative to the pristine graphene. As the ratio of hydrogen and carbon is 1:3, the periodically hydrogenated graphene is named “one‐third‐hydrogenated graphene” (OTHG). The area of OTHG is up to 16 mm². Density functional theory calculations demonstrate that the OTHG has two deformed Dirac cones along one high‐symmetry direction and a finite energy gap along the other directions at the Fermi energy, indicating strong anisotropic electrical properties. An efficient method is thus provided to produce large‐scale crystalline functionalized graphene with specially desired properties.     

Generalized Synthesis of Ultrathin Cobalt‐Based Nanosheets from Metallophthalocyanine‐Modulated Self‐Assemblies for Complementary Water Electrolysis

The development of effective approaches for preparing large‐area, self‐standing, ultrathin metal‐based nanosheets, which have proved to be favorable for catalytic applications such as water electrolysis, is highly desirable but remains a great challenge. Reported herein is a simple and versatile strategy to synthesize ultrathin Co₃O₄ and CoP NSs consisting of close‐packed nanoparticles by pyrolyzing cobalt(II) phthalocyanine/graphene oxide (CoPc/GO) assemblies in air and subsequent topotactic phosphidation while preserving the graphene‐like morphology. The strong π–π stacking interactions between CoPc and GO, and the inhibiting effect of the tetrapyrrole‐derived macrocycle for grain growth during the catalytic carbon gasification contribute to the NSs forming. The resulting homologous Co₃O₄ and CoP NSs display outstanding catalytic activity in alkaline media toward the oxygen evolution reaction and the hydrogen evolution reaction, respectively, ascribed to the richly exposed active sites, and the expedited electrolyte/ion transmission path. The integrated asymmetrical two‐electrode configuration also presents a superior cell voltage of 1.63 V at 10 mA cm^?2 for overall water splitting, accompanied with the excellent durability during long‐term cycling. Further evidences validate that this strategy is appropriate to fabricate graphene‐like ultrathin NSs of many other metal oxides, such as Fe₂O₃, NiO, MoO₃, and mixed‐metal oxides, for various applications.