Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

Recent progress in preventive effect of collagen peptides on photoaging skin and action mechanism

Ultraviolet(UV)-induced photoaging skin has become an urgent issue.The functional foods and cosmetics aiming to improve skin photoaging are developing rapidly,and the demand is gradually increasing year by year.Collagen peptides have been proven to display diverse physiological activities,such as excellent moisture retention activity,hygroscopicity,tyrosinase inhibitory activity and antioxidant activity,which indicates that they have great potential in amelioration of UV-induced photoaging.The main objective of this article is to recap the main mechanisms to improve photoaging skin by collagen peptides and their physiological activities in photo-protection.Furthermore,the extraction and structural characteristics of collagen peptides are overviewed.More importantly,some clinical trials on the beneficial effect on skin of collagen peptides are also discussed.In addition,prospects and challenges of collagen peptides are emphatically elucidated in this review.This article implies that collagen peptides have great potential as an effective ingredient in food and cosmetics industry with a wide application prospect.

Nano-Graphene Oxide for Cellular Imaging and Drug Delivery

Two-dimensional graphene offers interesting electronic,thermal,and mechanical properties that are currently being explored for advanced electronics,membranes,and composites.Here we synthesize and explore the biological applications of nano-graphene oxide(NGO),i.e.,single-layer graphene oxide sheets down to a few nanometers in lateral width.We develop functionalization chemistry in order to impart solubility and compatibility of NGO in biological environments.We obtain size separated pegylated NGO sheets that are soluble in buffers and serum without agglomeration.The NGO sheets are found to be photoluminescent in the visible and infrared regions.The intrinsic photoluminescence(PL)of NGO is used for live cell imaging in the near-infrared(NIR)with little background.We found that simple physisorption viaπ-stacking can be used for loading doxorubicin,a widely used cancer drug onto NGO functionalized with antibody for selective killing of cancer cells in vitro.Owing to its small size,intrinsic optical properties,large specifi c surface area,low cost,and useful non-covalent interactions with aromatic drug molecules,NGO is a promising new material for biological and medical applications.

Carbon Nanotubes in Biology and Medicine:In vitro and in vivo Detection,Imaging and Drug Delivery

Carbon nanotubes exhibit many unique intrinsic physical and chemical properties and have been intensively explored for biological and biomedical applications in the past few years.In this comprehensive review,we summarize the main results from our and other groups in this field and clarify that surface functionalization is critical to the behavior of carbon nanotubes in biological systems.Ultrasensitive detection of biological species with carbon nanotubes can be realized after surface passivation to inhibit the non-specific binding of biomolecules on the hydrophobic nanotube surface.Electrical nanosensors based on nanotubes provide a label-free approach to biological detection.Surface-enhanced Raman spectroscopy of carbon nanotubes opens up a method of protein microarray with detection sensitivity down to 1 fmol/L.In vitro and in vivo toxicity studies reveal that highly water soluble and serum stable nanotubes are biocompatible,nontoxic,and potentially useful for biomedical applications.In vivo biodistributions vary with the functionalization and possibly also size of nanotubes,with a tendency to accumulate in the reticuloendothelial system(RES),including the liver and spleen,after intravenous administration.If well functionalized,nanotubes may be excreted mainly through the biliary pathway in feces.Carbon nanotube-based drug delivery has shown promise in various In vitro and in vivo experiments including delivery of small interfering RNA(siRNA),paclitaxel and doxorubicin.Moreover,single-walled carbon nanotubes with various interesting intrinsic optical properties have been used as novel photoluminescence,Raman,and photoacoustic contrast agents for imaging of cells and animals.Further multidisciplinary explorations in this field may bring new opportunities in the realm of biomedicine.

TiO_(2) Nanocrystals Grown on Graphene as Advanced Photocatalytic Hybrid Materials

A graphene/TiO_(2) nanocrystals hybrid has been successfully prepared by directly growing TiO_(2) nanocrystals on graphene oxide(GO)sheets.The direct growth of the nanocrystals on GO sheets was achieved by a two-step method,in which TiO_(2) was first coated on GO sheets by hydrolysis and crystallized into anatase nanocrystals by hydrothermal treatment in the second step.Slow hydrolysis induced by the use of EtOH/H2O mixed solvent and addition of H2SO4 facilitates the selective growth of TiO_(2) on GO and suppresses growth of free TiO_(2) in solution.The method offers easy access to the GO/TiO_(2) nanocrystals hybrid with a uniform coating and strong interactions between TiO_(2) and the underlying GO sheets.The strong coupling gives advanced hybrid materials with various applications including photocatalysis.The prepared graphene/TiO_(2) nanocrystals hybrid has superior photocatalytic activity to other TiO_(2) materials in the degradation of rhodamine B,showing an impressive three-fold photocatalytic enhancement over P25.It is expected that the hybrid material could also be promising for various other applications including lithium ion batteries,where strong electrical coupling to TiO_(2) nanoparticles is essential.

A mini review on nickel-based electrocatalysts for alkaline hydrogen evolution reaction

High gravimetric energy density, earth-abundance, and environmental friendliness of hydrogen sources have inspired the utilization of hydrogen fuel as a clean alternative to fossil fuels. Hydrogen evolution reaction （HER）, a half reaction of water splitting, is crucial to the low-cost production of pure H2 fuels but necessitates the use of electrocatalysts to expedite reaction kinetics. Owing to the availability of low-cost oxygen evolution reaction （OER） catalysts for the counter electrode in alkaline media and the lack of low-cost OER catalysts in acidic media, researchers have focused on developing HER catalysts in alkaline media with high activity and stability. Nickel is well-known as an HER catalyst and continuous efforts have been undertaken to improve Ni-based catalysts as alkaline electrolyzers： In this review, we summarize earlier studies of HER activity and mechanism on Ni surfaces, along with recent progress in the optimization of the Ni-based catalysts using various modern techniques. Recently developed Ni-based HER catalysts are categorized according to their chemical nature, and the advantages as well as limitations of each category are discussed. Among all Ni-based catalysts, Ni-based alloys and Ni-based hetero-structure exhibit the most promising electrocatalytic activity and stability owing to the fine-tuning of their surface adsorption properties via a synergistic nearby element or domain. Finally, selected applications of the developed Ni-based HER catalysts are highlighted, such as water splitting, the chloralkali process, and microbial electrolysis cell.

High Performance In Vivo Near-IR (>1 μm) Imaging and Photothermal Cancer Therapy with Carbon Nanotubes

Short single-walled carbon nanotubes(SWNTs)functionalized by PEGylated phospholipids are biologically non-toxic and long-circulating nanomaterials with intrinsic near infrared photoluminescence(NIR PL),characteristic Raman spectra,and strong optical absorbance in the near infrared(NIR).This work demonstrates the first dual application of intravenously injected SWNTs as photoluminescent agents for in vivo tumor imaging in the 1.0-1.4μm emission region and as NIR absorbers and heaters at 808 nm for photothermal tumor elimination at the lowest injected dose(70μg of SWNT/mouse,equivalent to 3.6 mg/kg)and laser irradiation power(0.6 W/cm2)reported to date.Ex vivo resonance Raman imaging revealed the SWNT distribution within tumors at a high spatial resolution.Complete tumor elimination was achieved for large numbers of photothermally treated mice without any toxic side effects after more than six months post-treatment.Further,side-by-side experiments were carried out to compare the performance of SWNTs and gold nanorods(AuNRs)at an injected dose of 700μg of AuNR/mouse(equivalent to 35 mg/kg)in NIR photothermal ablation of tumors in vivo.Highly effective tumor elimination with SWNTs was achieved at 10 times lower injected doses and lower irradiation powers than for AuNRs.These results suggest there are significant benefits of utilizing the intrinsic properties of biocompatible SWNTs for combined cancer imaging and therapy.

A mini-review on rare-earth down-conversion nanoparticles for NIR-II imaging of biological systems

Rare-earth(RE)based luminescent probes exhibit rich optical properties including upconversion and down-conversion luminescence spanning a broad spectral range from 300 to 3,000 nm,and have generated great scientific and practical interest from telecommunication to biological imaging.While upconversion nanoparticles have been investigated for decades,down-conversion luminescence of RE-based probes in the second near-infrared(NIR-II,1,000-1,700 nm)window for in vivo biological imaging with sub-centimeter tissue penetration and micrometer image resolution has come into light only recently.In this review,we present recent progress on RE-based NIR-II probes for in vivo vasculature and molecular imaging with a focus on Er3+-based nanoparticles due to the down-conversion luminescence at the long-wavelength end of the NIR-II window(NIR-IIb,1,500-1,700 nm).Imaging in NIR-IIb is superior to imaging with organic probes such as ICG and IRDye800 in the^800 nm NIR range and the 1,000-1,300 nm short end of NIR-II range,owing to minimized light scattering and autofluorescence background.Doping by cerium and other ions and phase engineering of Er^3+-based nanoparticles,combined with surface hydrophilic coating optimization can afford ultrabright,biocompatible NIR-IIb probe towards clinical translation for human use.The Nd^3+-based probes with NIR-II emission at 1,050 and 1,330 nm are also discussed,including Nd^3+doped nanocrystals and Nd^3+-organic ligand complexes.This review also points out future directions for further development of multi-functional RE NIR-II probes for biological imaging.

Biological imaging without autofluorescence in the second near-infrared region

Fluorescence imaging is capable of acquiring anatomical and functional infor- mation with high spatial and temporal resolution. This imaging technique has been indispensable in biological research and disease detection/diagnosis. Imaging in the visible and to a lesser degree, in the near-infrared （NIR） regions below 900 nm, suffers from autofluorescence arising from endogenous fluorescent molecules in biological tissues. This autofluorescence interferes with fluorescent molecules of interest, causing a high background and low detection sensitivity. Here, we report that fluorescence imaging in the 1,500-1,700-nm region （termed ＂NIR-IIb＂） under 808-nm excitation results in nearly zero tissue autofluorescence, allowing for background-free imaging of fluorescent species in otherwise notoriously autofluorescent biological tissues, including liver. Imaging of the intrinsic fluorescence of individual fluorophores, such as a single carbon nanotube, can be readily achieved with high sensitivity and without autofluorescence background in mouse liver within the 1,500-1,700-nm wavelength region.

A theranostic agent for cancer therapy and imaging in the second nearinfrared window

Thera no stic nano particles are integrated systems useful for simulta neous diag nosis and imaging guided delivery of therapeutic drugs, with wide ranging pote ntial applicati ons in the clinic. Here we developed a thera no stic nan oparticle (~24 nm size by dynamic light scatteri ng) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-Ⅱ) window and an an ti-ca ncer drug paclitaxel. Folic acid (FA) was conjugated to the nan oparticles to afford specific binding to molecular folate receptors on muri ne breast can cer 4T1 tumor cells. In vivo, the nan oparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0±2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-Ⅱ theranostic age nt developed.

WS2 nanoflakes from nanotubes for electrocatalysis

Next-generation catalysts for water splitting are crucial towards a renewable hydrogen economy. MoS2 and WS2 represent earth-abundant, noble metal cathode alternatives with high catalytic activity at edge sites. One challenge in their development is to nanostructure these materials in order to achieve increased performance through the creation of additional edge sites. In this work, we demonstrate a simple route to form nanostructured-WS2 using sonochemical exfoliation to break interlayer and intralayer bonds in WS2 nanotubes. The resulting few-layer nanoflakes are -100 nm wide with a high density of edge sites. WS2 nanoflakes are utilized as cathodes for the hydrogen evolution reaction （HER） and exhibit superior performance to WS2 nanotubes and bulk particles, with a lower onset potential, shallower Tafel slope and increased current density. Future work may employ ultra-small nanoflakes, dopant atoms, or graphene hybrids to further improve electrocatalytic activity.

Multiplexed Five-Color Molecular Imaging of Cancer Cells and Tumor Tissues with Carbon Nanotube Raman Tags in the Near-Infrared

Single-walled carbon nanotubes(SWNTs)with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specificity.Multiplexed Raman imaging of live cells has been carried out by highly specific staining of cells with a five-color mixture of SWNTs.Ex vivo multiplexed Raman imaging of tumor samples uncovers a surprising up-regulation of epidermal growth factor receptor(EGFR)on LS174T colon cancer cells from cell culture to in vivo tumor growth.This is the first time five-color multiplexed molecular imaging has been performed in the near-infrared(NIR)region under a single laser excitation.Near zero interfering background of imaging is achieved due to the sharp Raman peaks unique to nanotubes over the low,smooth autofluorescence background of biological species.

Aligned Graphene Nanoribbons and Crossbars from Unzipped Carbon Nanotubes

Aligned graphene nanoribbon (GNR) arrays have been made by unzipping of aligned single-walled and few-walled carbon nanotube (CNT) arrays. Nanotube unzipping was achieved by a polymer-protected Ar plasma etching method, and the resulting nanoribbon array can be transferred onto any chosen substrate. Atomic force microscope (AFM) imaging and Raman mapping on the same CNTs before and after unzipping confirmed that ~80% of CNTs were opened up to form single layer sub-10 nm GNRs. Electrical devices made from the GNRs (after annealing in H2 at high temperature) showed on/off current (Ion/Ioff) ratios up to 103 at room temperature, suggesting the semiconducting nature of the narrow GNRs. Novel GNR-GNR and GNR-CNT crossbars were fabricated by transferring GNR arrays across GNR and CNT arrays, respectively. The production of such ordered graphene nanoribbon architectures may allow for large scale integration of GNRs into nanoelectronics or optoelectronics.

An electrodeposition approach to metal/metal oxide heterostructures for active hydrogen evolution catalysts in near-neutral electrolytes

Neutral water splitting is attractive for its use of non-corrosive and environmentally friendly electrolytes.However,catalyst development for hydrogen and oxygen evolution remains a challenge under neutral conditions.Here we report a simple electrodeposition and reductive annealing procedure to produce a highly active Ni-Co-Cr metal/metal oxide heterostructured catalyst directly on Ni foam.The resulting electrocatalyst for hydrogen evolution reaction (HER) requires only 198 mV of overpotential to reach 100 mNcm2 in 1 M potassium phosphate (pH =7.4) and can operate for at least two days without significant performance decay.Scanning transmission electron microscopy coupled with electron energy loss spectroscopy (STEM-EELS) imaging reveals a Ni-Co alloy core decorated with blended oxides layers of NiO,CoO and Cr2O3.The metal/metal oxide interfaces are suggested to be responsible for the high HER activity.

Nickel-coated silicon photocathode for water splitting in alkaline electrolytes

Photoelectrochemical （PEC） water splitting is a promising approach to harvest and store solar energy [1]. Silicon has been widely investigated for PEC photoelectrodes due to its suitable band gap （1.12 eV） matching the solar spectrum [2]. Here we investigate employing nickel both as a catalyst and protecting layer of a p-type silicon photocathode for photoelectrochemical hydrogen evolution in basic electrolytes for the first time. The silicon photocathode was made by depositing 15 nm Ti on a p-type silicon wafer followed by 5 nm Ni. The photocathode afforded an onset potential of -0.3 V vs. the reversible hydrogen electrode （RHE） in alkaline solution （1 M KOH）. The stability of the Ni/Ti/p-Si photocathode showed a 100 mV decay over 12 h in KOH, but the stability was significantly improved when the photocathode was operated in potassium borate buffer solution （pH ≈ 9.5）. The electrode surface was found to remain intact after 12 h of continuous operation at a constant current density of 10 mA/cm^2 in potassium borate buffer, suggesting that Ni affords good protection of Si based photocathodes in borate buffers.

Chemical Self-Assembly of Graphene Sheets

Chemically derived and noncovalently functionalized graphene sheets(GS)were found to self-assemble onto patterned gold structures via electrostatic interactions between the functional groups and the gold surfaces.This afforded regular arrays of single graphene sheets on large substrates,which were characterized by scanning electron microscopy(SEM),Auger microscopy imaging,and Raman spectroscopy.This represents the fi rst time that self-assembly has been used to produce on-substrate and fully-suspended graphene electrical devices.Molecular coatings on the GS were removed by high current“electrical annealing”,which restored the high electrical conductance and Dirac point of the GS.Molecular sensors for highly sensitive gas detection using the self-assembled GS devices are demonstrated.

Multiplexed cytokine detection on plasmonic gold substrates with enhanced near-infrared fluorescence

Protein microarrays based on fluorescence detection have been widely utilized for high-throughput functional proteomic analysis. However, a drawback of such assays has been low sensitivity and narrow dynamic range, limiting their capabilities, especially for detecting low abundance biological molecules such as cytokines in human samples. Here, we present fluorescence-enhancing microarrays on plasmonic gold films for multiplexed cytokine detection with up to three orders of magnitude higher sensitivity than on conventional nitrocellulose and glass substrates. Cytokine detection on the gold plasmonic substrate is about one to two orders of magnitude more sensitive than enzyme-linked immunosorbent assay （ELISA） and can be multiplexed. A panel of six cytokines （Vascular endothelial growth factor （VEGF）, Interleukin 1β （IL-1β）, Interleukin 4 （IL-4）, Interleukin 6 （IL-6）, Interferon γ （IFN-γ）, and Tumor necrosis factor （TNF）） were detected in the culture media of cancer cells. This work establishes a new method of high throughput multiplexed cytokine detection with higher sensitivity and dynamic range than ELISA.

Projected Performance Advantage of Multilayer Graphene Nanoribbons as a Transistor Channel Material

The performance limits of a multilayer graphene nanoribbon(GNR)field-effect transistor(FET)are assessed and compared with those of a monolayer GNRFET and a carbon nanotube(CNT)FET.The results show that with a thin high dielectric constant(high-κ)gate insulator and reduced interlayer coupling,a multilayer GNRFET can significantly outperform its CNT counterpart with a similar gate and bandgap in terms of the ballistic on-current.In the presence of optical phonon scattering,which has a short mean free path in the graphene-derived nanostructures,the advantage of the multilayer GNRFET is even more significant.Simulation results indicate that multilayer GNRs with incommensurate non-AB stacking and weak interlayer coupling are the best candidates for high-performance GNRFETs.

Rational Design of High Brightness NIR-II Organic Dyes with S‑D-AD‑S Structure

CONSPECTUS:Fluorescence bioimaging in the second nearinfrared window(NIR-II,1000−1700 nm)is a superior visualization tool with deeper penetration and higher spatial resolution than the traditional vis/NIR window(400−1000 nm).Developing desirable NIR-II agents with high brightness(high quantum yield(QY)and absorption coefficient),longer emission wavelengths,light stability,and good biocompatibility is a bottleneck that must be crossed in the process of clinical transformation.NIR-II organic agents attract more attention because of their good biocompatibility.Researchers are committed to develop small organic molecules with an adjustable narrow band gap to emit longer NIR-II wavelengths.However,the reduced band gap of molecular fluorophores generally triggered interactions between the conjugated skeleton and other molecules,leading to a decreased fluorescence QY,especially quenching in aqueous systems.Aiming to enhance NIR-II fluorophores’brightness in aqueous systems,the molecular engineering of a shielding and donor unit is introduced in NIR-II fluorophores,and these molecules are composed of a shielding unit,donor(s),acceptor,donor(s),shielding unit(S-D-A-D-S)structure.We found that the donor’s steric hindrance brings about a molecular twist that can be tuned with electrostatic potential surfaces and the donor’s hydrophobic effects,which can reduce water molecules approaching the excitation center.In addition to the protective effect of the electron shielding units,these changes can be weakened by the interactions between water and fluorophore molecules,which is beneficial to the stability of excited states for fluorophore brightness maintained in watersoluble environments.However,the molecular torsion will reduce intramolecular charge transfer(ICT),the weakened transition from the ground state to the excited state(S_(0)−S_(1)),leading to an undesired decrease in the absorption coefficient.Thus,it is necessary to develop molecular engineering to improve emission QY without sacrificing the absorption coefficient.Therefore,bright NIR-II fluorophores need to have a rational balanced donor unit,which can have decreased backbone distortion to strengthen ICT and better protect the conjugated backbone to reduce the water molecule effect,resulting in improvements to the QY and absorption coefficient simultaneously.In this Account,we will present a concise summary and analysis of the rational molecular design of S-D-A-D-S structural NIR-II fluorophores for tunable enhanced QY and absorption coefficients based on the shielding and donor engineering strategy.We expect that this Account will trigger more research interest to explore the inspiring performance of S-D-A-D-S structural NIR-II fluorophores and employ them in bioimaging to promote the process of clinical transformation.

The inaugural Nano Research Young Innovators （NR45） Award in nanobiotechnology

It is our great pleasure to announce awardees of the inaugural 2018 Nano Research Young Innovators （NR45） in nanobiotechnology. Congratulations to all of the 45 outstanding young investigators under 45! They were selected through a competitive process by an award committee from our editorial board. Nano Research is launching the NR45 Award program to young researchers in various fields of nanoscience and nanotechnology, in recognition to their distinguished accomplishments and/or potential to make substantial contributions to their fields. The aim of Nano Research NR45 is to recognize the outstanding contributions of young scientists and together with the Nano Research Symposium integrated in the annual US-SINO Nano Forum provide a platform for communication, discussions and collaborations between scientists inter- nationally. For this inaugural year.