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In this work, we describe the preparation and use of a thin metal film modified Indium Tin Oxide (ITO) electrode as a highly conductive, transparent, and electrocatalytically active electrode material for studying nanobubbles generated at the electrode/solution interface. Hydrogen and oxygen nanobubbles were generated from water electrolysis on the surface of a Au/Pd alloy modified ITO electrode. The formation of single H2 and O2 nanobubbles was imaged in real time during a potential scan using single-molecule fluorescence microscopy. Our results show that while O2 nanobubbles can be detected at an early stage in the oxygen evolution reaction (OER), the formation of H2 nanobubbles requires a significant overpotential. Our study shows that thin-film-coated ITO electrodes are simple to make and can be useful electrode substrates for (single molecule) spectroelectrochemistry research.

The glycemic indices (GI) of pea and chickpea are normally lower than 60, which are commonly considered as middle or low GI foods. Different processing conditions would influence proportions of rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS) in the processed pea and chickpea. In general, high-temperature cooking followed by high-temperature drying (HCHD) largely kept total starch (68.58% and 61.99% of dry matter in pea and chickpea, respectively), increased RDS (29.89% and 33.40% of total starch in pea and chickpea, respectively) and RS proportions (25.78% and 17.08% of total starch in pea and chickpea, respectively) while the opposite effect in pea and chickpea was observed. Glycemic response of panelists after consuming HCHD pea or chickpea would cause a faster increase of incremental plasma glucose concentration within 30 min, followed by a rapid decrease to baseline compared with the pea or chickpea processed by low-temperature cooking followed by low-temperature drying (LCLD). The GI of HCHD pea and chickpea were 59.02 and 49.15, respectively, which were significantly higher than those processed by LCLD (pea: 32.63, chickpea: 31.91). Both in vitro and in vivo digestibility indicated that LCLD was more suitable to process pea and chickpea powder.

The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO43−, when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.

AlkB homolog 5 (ALKBH5) has been reported as a key m6A demethylase that is involved in development and diseases; however, the function of ALKBH5 in osteogenesis remains unknown. In this study, we report that ALKBH5 mRNA and protein expression were upregulated during osteoblast differentiation and that ALKBH5 knockdown suppressed osteoblast differentiation, mineralization, and the expression of osteogenic biomarkers. Conversely, ALKBH5 overexpression promoted osteogenesis. Moreover, the expression of wild-type ALKBH5, but not the m6A-modified active site mutant ALKBH5, could rescue ALKBH5 knockdown-induced osteogenesis inhibition. Furthermore, knockdown of ALKBH5 significantly impaired the mRNA stability of the transcription factor Runx2, which plays a key role in osteoblast differentiation. Taken together, our results suggest that ALKBH5 promotes osteogenesis through modulating Runx2 mRNA stability.

Photodynamic therapy is widely used in clinics and for anti-bacterial applications. The major challenge is the limited depth of tissue penetration of light and poor targetability. In this study, magnetite nanoparticles were used as a highly sensitive T2-weighted MR imaging contrast agents to target the tumor and mimic horseradish peroxidase (HRP), which could catalyze the decomposition of hydrogen peroxide to generate reactive oxygen species (ROS) to inhibit the tumor in vivo. In these experiments, MNPs were demonstrated to possess the enzyme-mimicking activity in different pH values, and the activity was dependent on the size of the MNPs: the smaller the size, the higher the activity. We demonstrated that MNPs showed highly efficient anti-bacterial (E. coli) activity in presence of H2O2. The E. coli inhibition ratio reached nearly 100% at optimal concentration. The anti-tumor activity was evaluated through HeLa cell viability under treatment with MNPs and H2O2. Consequently, the cell viability was significantly decreased and more than 80% of HeLa cells were dead after treatment with MNPs and H2O2 under different pH values. MR imaging was used to demonstrate the tumor targetability of 13 nm MNPs in vitro and in vivo. Consequently, the relaxivity of the 13 nm MNPs was determined to be r2 = 104 s-1 mM-1. The MR signal was much more negative and the intensity was significantly diminished with the increase of the concentration of 13 nm MNPs in vitro. The tumor signal was clearly visualized and a 3-fold decrease of the MR signal intensity of the tumor site of the mice was observed after 24 h-post treatment with the 13 nm MNPs. Finally, the tumor inhibition in vivo was investigated using 6 nm MNPs in BALB/c nude female mice bearing subcutaneously implanted HeLa cells on the right flank. The results show statistically significant efficacy in delaying tumor growth from day 6, and an approximately 99% tumor inhibition ratio was shown by the combination of MNPs and H2O2 after treatment for 17 days. By leveraging the passive targeting and MR imaging properties, we expect that the enzyme-mimicking MNPs could be used for cancer theranostics and may open up a new avenue for the treatment of epidermal infections.

We report the observation of electrocatalytic water oxidation during transient collision and oxidation of single-Ag nanoparticles (NPs) on a gold ultra-microelectrode (UME). Collision and oxidation of single-Ag NPs are studied under higher positive potentials (≥1 V versus Ag/AgCl electrode) on a gold UME than previously used. The use of higher potentials allows us to observe several unique features not seen at lower potentials (0.6–0.8 V), including a greatly increased collision frequency and the appearance of subcollision peaks with a long current tail. Moreover, the average charge transferred in a collision event is 3–5 times more than that estimated from a complete NP oxidation. Our results suggest that the enhanced charge transfer is due to coupled water oxidation catalyzed by Ag oxide transiently formed upon NP collision. A pH-dependence study was further performed to reveal a characteristic feature of water oxidation, and the formation of silver oxide was directly confirmed by single-NP fluorescence...

Summary The field of single-molecule electrochemistry has seen many exciting advances since Bard and Fan demonstrated the use of redox cycling. Recent development of nanoelectrodes and microfabricated nanogap devices has enabled reproducible measurements of single redox molecules. Fluorescence and Raman spectroscopy are increasingly used to probe individual heterogeneous electron-transfer events. The use of bipolar coupling may allow optical recording of single redox events for conventional redox species.

In this Technical Note, we describe a method to fabricate nanopore-supported Pt nanoparticle electrodes and their use in bipolar electrochemistry. A Pt nanoparticle is deposited on the orifice of a solid-state nanopore inside a focused-ion beam (FIB) system. Complete blockage of the nanopore with Pt metal forms a closed bipolar nanoparticle electrode whose size and shape can be tunable in one simple step. Nanoparticle electrodes and their arrays can be prepared on different substrates such as the tip of a glass pipet, a double-barrel pipet, and a freestanding silicon nitride membrane. Steady-state voltammetry can be performed on such nanoparticle electrodes via bipolar electrochemistry. Moreover, an array of Pt nanoparticles can be used for fluorescence-enabled electrochemical microscopy. Future use of highly advanced FIB systems may allow nanoparticles of10 nm to be fabricated which may enable coupled electrochemical reactions of single redox molecules. Pipette-supported single particle electrodes may also find useful applications in high resolution imaging with nanoscale scanning electrochemical microscopy (SECM) and neurochemical analysis inside single cells.

Here we report the direct observation and quantitative analysis of single redox events on a modified indium–tin oxide (ITO) electrode. The key in the observation of single redox events are the use of a fluorogenic redox species and the nanoconfinement and hindered redox diffusion inside 3-nm-diameter silica nanochannels. A simple electrochemical process was used to grow an ultrathin silica film (~100 nm) consisting of highly ordered parallel nanochannels exposing the electrode surface from the bottom. The electrode-supported 3-nm-diameter nanochannels temporally trap fluorescent resorufin molecules resulting in hindered molecular diffusion in the vicinity of the electrode surface. Adsorption, desorption, and heterogeneous redox events of individual resorufin molecules can be studied using total-internal reflection fluorescence (TIRF). The rate constants of adsorption and desorption processes of resorufin were characterized from single-molecule analysis to be (1.73 ± 0.08) × 10−4 cm·s−1 and 15.71 ± 0.76 s−1, respectively. The redox events of resorufin to the non-fluorescent dihydroresorufin were investigated by analyzing the change in surface population of single resorufin molecules with applied potential. The scan-rate-dependent molecular counting results (single-molecule fluorescence voltammetry) indicated a surface-controlled electrochemical kinetics of the resorufin reduction on the modified ITO electrode. This study demonstrates the great potential of mesoporous silica as a useful modification scheme for studying single redox events on a variety of transparent substrates such as ITO electrodes and gold or carbon film coated glass electrodes. The ability to electrochemically grow and transfer mesoporous silica films onto other substrates makes them an attractive material for future studies in spatial heterogeneity of electrocatalytic surfaces.

Nucleation and growth of hydrogen nanobubbles are key initial steps in electrochemical water splitting. These processes remain largely unexplored due to a lack of proper tools to probe the nanobubble’s interfacial structure with sufficient spatial and temporal resolution. We report the use of superresolution microscopy to image transient formation and growth of single hydrogen nanobubbles at the electrode/solution interface during electrocatalytic water splitting. We found hydrogen nanobubbles can be generated even at very early stages in water electrolysis, i.e., ∼500 mV before reaching its thermodynamic reduction potential. The ability to image single nanobubbles on an electrode enabled us to observe in real time the process of hydrogen spillover from ultrathin gold nanocatalysts supported on indium–tin oxide.

Co-self-assembled vesicular nanoparticles of two structurally comparable amphiphilic boron-dipyrromethene (BODIPY) dyes with dequenchable dual colour fluorescence were prepared for ratiometric imaging of live cells.

The electrochemical interface is an ultrathin interfacial region between the electrode surface and the electrolyte solution and is often characterized by numerous dynamic processes, such as solvation and desolvation, heterogeneous electron transfer, molecular adsorption and desorption, diffusion, and surface rearrangement. Many of these processes are driven and modulated by the presence of a large interfacial potential gradient. The study and better understanding of the electrochemical interface is important for designing better electrochemical systems where their applications may include batteries, fuel cells, electrocatalytic water splitting, corrosion protection, and electroplating. This, however, has proved to be a challenging analytical task due to the ultracompact and dynamic evolving nature of the electrochemical interface. Here, we describe the use of an electrochemical nanocell to image the dynamic collision and oxidation process of single silver nanoparticles at the surface of a platinum nanoelectrode. A nanocell is prepared by depositing a platinum nanoparticle at the tip of a quartz nanopipette forming a bipolar nanoelectrode. The compact size of the nanocell confines the motion of the silver nanoparticle in a 1-D space. The highly dynamic process of nanoparticle collision and oxidation is imaged by single-particle fluorescence microscopy. Our results demonstrate that silver nanoparticle collision and oxidation is highly dynamic and likely controlled by a strong electrostatic effect at the electrode/solution interface. We believe that the use of a platinum nanocell and single molecule/nanoparticle fluorescence microscopy can be extended to other systems to yield highly dynamic information about the electrochemical interface.

The spontaneous release of drug payloads in the whole body always results in the compromised drug bioavailability and ultimate therapeutic efficacy. To achieve enhanced therapeutic efficacy and reduced side effects, pH-responsive targeted drug delivery systems have been studied due to their enhanced tumor accumulation and controllable maximum drug release feature. The present study described a co-assembly constructed by a pH responsive molecule (i.e., malachite green carbinol base (MG)) and liposome for highly efficient doxorubicin (DOX) release in tumor cells ( MG–DOX ⊂ L ). The structural transformation of MG effectively regulates the drug release profile in acidic environment. The pH-responsive sensitivity of co-assembly can be fine-tuned by altering the mixing ratios of building blocks with pH responders (i.e., MG molecules). MG–DOX ⊂ L was beneficial for the DOX release at pH 5.0 and showed a higher cytotoxicity in KB cells owing to the pH-responsive drug release in acidic organelles following endocytosis pathway. In vivo tumor targetability and growth inhibition were evaluated in KB cell-xenografted nude mice. We have demonstrated that effective tumor growth inhibition in vivo is attributed to the synergistic contributions from highly efficient cellular entry and responsive intracellular release of DOX from MG–DOX ⊂ L .

We report a convenient synthetic approach for one-pot preparation of poly(β-amino ester)s copolymerized with peptides. A family of copolymers with tertiary amine groups was synthesized by copolymerizing di(ethylene glycol) diacrylate (DEDA), poly(ethylene glycol) diacrylate (PEGDA), 3-(diethylamino)propylamine (DEPA) and GGRGD peptides using the Michael addition reaction. The hydrophobic/hydrophilic properties of the resulting copolymers are adjusted by altering the feed ratios of DEDA and PEGDA. The copolymers self-assembled into nanoparticles with sizes around 60–140 nm in aqueous media, which were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques. The copolymers exhibit pH sensitive properties upon introduction of DEPA moieties, which were proved by pyrene fluorescence and pH titration measurements. The acid-triggered dissociation behaviors of the nanoparticles were studied by DLS and Nile red (NR) release experiments, revealing that the sizes of dissociated copolymer nanoparticles were closely relevant to their compositions. The nanoparticles can load the hydrophobic anticancer drug, i.e., doxorubicin (DOX). The DOX-loaded nanoparticles were stable in a neutral phosphate buffer solution with a payload leakage less than 20% at 37 °C. However, a significant acid-triggered DOX release was accomplished at pH 5.0 with release efficiency up to 60–80%. Because of the decoration of Arg-Gly-Asp (RGD) peptides onto the poly(β-amino ester)s, the DOX-encapsulated nanoparticles formed by poly(RGD-co-β-amino ester)s can be internalized by cancer cells via an αvβ3 integrin-mediated endocytosis pathway and accumulated in the lysosomes that provide an acidic environment to promote the release of DOX. Finally, the DOX-encapsulated copolymer nanoparticles with the targeted RGD peptide exhibited higher efficiency to kill U87 human glioblastoma cancer cells than that without RGD, which was further proved by cellular uptake of DOX-loaded nanoparticles.

The matrix metalloproteinases (MMPs) are a family of proteases which are normally up-regulated in tumor tissues. Gelatin is a biocompatible and non-immunogenic substrate which can be degraded by MMPs. In this work, MMPs-degradable gelatin coated mesoporous silica nanoparticles (MSNs@Gel) were designed for endogenous tumor microenvironment-triggered release systems for cancer treatment in vivo. This drug delivery system is expected to attain preferential release of drugs in tumor microenvironment with diminished systemic toxicity. The gelatin corona can serve as both a protective layer for preventing drugs leakage and MMPs-digested substrates for responding the solid tumor microenvironment. Doxorubicin (DOX), as a model antitumor drug, was loaded into the mesopores of MSNs@Gel to give DOX⊂MSNs@Gel with controllable releasing feature upon the MMPs stimuli. Interestingly, the encapsulated DOX in the DOX⊂MSNs@Gel was barely delivered into the normal cells due to the less endocytosis activity compared to that of the cancerous cells, resulting in the decreased systemic toxicity and decreased side effect during the tumor treatment. Whilst in the tumor tissue, the gelatin layer of DOX⊂MSNs@Gel was degraded and the encapsulated DOX was released effectively. The released DOX was accumulated in the nucleus of tumor cells. In vivo studies demonstrated that the tumor growth of xenografted mice was significantly delayed without any appreciable body weight loss that indicated the lower systemic toxicity of DOX⊂MSNs@Gel compared to the free DOX.