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Abstract: Crystalline carbon nitride films have been synthesized on polycrystalline Ni substrates by a microwave plasma chemical vapour deposition technique, using a mixture of N2, CH4 and H2 as precursor. Scanning electron microscopy shows that the film consisted of perfect crystals of short and long hexagonal bars, tetragonal bars and irregular particles. From the X-ray photoelectron spectroscopy (XPS) data, a maximum N/C ratio of 1.0 was achieved in the films. The XPS spectra of the film typically showed three peaks in the C 1s core spectrum (centered at 284.78, 285.94, and 287.64 eV) and two peaks in the N 1s core level spectrum (centered at 398.35 and 400.01 eV). This indicates that there are two types of C–N bonds; N is bonded to sp2- or sp3-coordinated C atoms in the as-deposited film. The X-ray diffraction pattern indicates that the film is composed of α-, β-, pseudocubic, graphitic C3N4 and an unidentified phase. A series of intense sharp Raman peaks were observed in the range of 100–1500 cm−1. These peaks match well with the calculated Raman frequencies of α- and β-C3N4, revealing the formation of α- and β-C3N4 phase. [Copyright &y& Elsevier]

[Display omitted] The present study aimed at constructing an oral nanoparticle delivery system loaded with tacrolimus (FK506) for effective treatment of inflammatory bowel disease. A FK506/HP-β-CD inclusion compound was prepared by grinding to increase drug solubility. To address the side- effects in non-target organs and systemic toxicity of FK506, pH-responsive Eudragit S100 (ES100) and hyaluronic acid (HA) with high affinity to CD44 receptor were adsorbed onto the surface of chitosan (CS) nanoparticles loaded with FK506/HP-β-CD through electrostatic interactions to obtain FK506@ES100/HA/CS/HP-β-CD nanoparticles (FK506@EHCh NPs). Caco-2 cells and Raw 264.7 macrophages were used to confirm the lack of cytotoxicity and good uptake ability of the newly generated nanoparticles. FK506@EHCh NPs significantly suppressed secretion of TNF-α, IL-1β and IL-6 by LPS-activated Raw 264.7 macrophages. A dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) murine model was established to further confirm the colon targeting and in vivo efficacy of oral IR-775@EHCh NPs. Based on the collective results, we conclude that packaging FK506 into active targeting nanocarriers sensitive to pH facilitates concentration of the drug within the sites of intestinal inflammation and improves the drug levels in target tissues, thus avoiding systemic side-effects and improving efficacy. In view of the promising results obtained in this study, the potential of EHCh nanoparticles for drug delivery and targeted treatment of inflammatory bowel disease warrants further investigation. [ABSTRACT FROM AUTHOR]

The detection of circulating tumor DNA (ctDNA) has increasingly received a great deal of attention considering its significance in cancer diagnosis. And the signal amplification plays an important role in the development of sensitive ctDNA biosensors. Herein, the nanocomposites (denoted as HAC-AuPt), integrating from high-active carbon (HAC) and AuPt alloy nanoparticles, were synthesized and subsequently used as a signal amplification label to fabricate a sandwich-type ctDNA electrochemical biosensor. Characterizations demonstrated that HAC presents uniform size distribution and AuPt alloy nanoparticles were successfully loaded on HAC. The current response could be amplified to a great extent by the resultant HAC-AuPt due to its excellent electrochemical property. The nanocomposites were further bounded with DNA signal probes (SPs) via Au-S or Pt-S assembly to form SPs-label. After the capture probes (CPs) were immobilized on the electrode surface, the target DNA (tDNA) and SPs-label were stepwise incubated on the CPs-modified electrode, thus forming a sandwich-type structure. By monitoring the catalytic signal of HAC-AuPt towards the reduction process of H 2 O 2 , this biosensor provided a wide linear range of 10−8 mol/L - 10−16 mol/L with a low detection limit of 3.6 × 10−17 mol/L (S/N = 3) for the detection of the tDNA. Furthermore, obvious differences in response signals among different DNAs were observed benefitting from the excellent selectivity of the biosensor. Besides, the long-term stability, reproducibility, and recovery rate were proved to be outstanding. These results indicate that the established biosensor holds a potential application in the clinical diagnosis of ctDNA. [Display omitted] • A sandwich-type ctDNA electrochemical biosensor was designed based on HAC-AuPt. • The HAC-AuPt contains high-active sites of N, graphitized-C, Co-Nx, and AuPt alloy. • The current signal could be amplified largely by the synthesized HAC-AuPt. • The biosensor exhibits satisfying sensitivity and high selectivity for ctDNA detection. [ABSTRACT FROM AUTHOR]

Here we presented a new facile strategy to fabricate ultrathin two-dimensional (2D) metal oxide nanosheets, by using polydopamine-coated graphene (rGO@PDA) as a template under simply wet-chemical conditions. Based on the strategy, graphene-like CeO 2 –TiO 2 mesoporous nanosheet (MNS-CeO 2 -TiO 2) was prepared and was loaded with dispersive Ag nanoparticles (AgNPs) to obtain effective electrocatalysts (denoted as Ag/MNS-CeO 2 -TiO 2) for electrochemical detection of superoxide anion (O 2 •−). Characterizations demonstrated that MNS-CeO 2 -TiO 2 exhibited ultrathin thickness, larger specific surface area, and pore volume in comparison with its bulk counterpart. The above properties of MNS-CeO 2 -TiO 2 shorten electron transmission distance, promotes mass transfer, and is conducive to the dispersion of post-modified AgNPs. Therefore, the recommended Ag/MNS-CeO 2 -TiO 2 sensors (denoted as Ag/MNS-CeO 2 -TiO 2 /SPCE) exhibited satisfactory properties, including the sensitivity of 737.1 μA cm−2 mM−1, the detection limit of 0.0879 μM (S/N = 3), and good selectivity. Meanwhile, the sensors also successfully realized in the online monitoring of O 2 •− released from HepG2 cells, meaning the prepared sensors had practical application potential towards the analysis of O 2 •− in biological samples. • A novel facile strategy for preparing ultrathin 2D metal oxide nanosheets was presented. • Based on above strategy, Ag/MNS-CeO 2 -TiO 2 were prepared with controllable morphology. • The superoxide anion (O 2 •−) electrochemical sensor was successfully fabricated with Ag/MNS-CeO 2 -TiO 2. [ABSTRACT FROM AUTHOR]

• MnFe 2 O 4 nanoparticles were evenly distributed on the rGO via a facile solvothermal method. • Synergetic effect of MnFe 2 O 4 and rGO provided enhanced performance for H 2 O 2 sensing. • MnFe 2 O 4 /rGO nanocomposites exhibited high current response with a LOD of 0.528 nM. Hydrogen peroxide (H 2 O 2) is a common oxidant and major active oxygen species in organisms. There is a great requirement for the accurate and rapid determination of H 2 O 2 in the fields of environmental analysis, clinical treatment, food safety, pharmaceuticals, etc. The electrochemical method is considered an ideal analytical technology due to its high sensitivity, fast response and low detection limit. Herein, a one-pot solvothermal synthesis method was used to prepare a manganese ferrite/reduced graphene oxide (MnFe 2 O 4 /rGO) composite, which was modified on the surface of home-made screen-printed electrodes to construct a new type of electrochemical sensor for the determination of H 2 O 2 , subsequently. Cyclic voltammetry and chronoamperometry were used to study the electrocatalytic performance of H 2 O 2 reduction in neutral conditions. The results showed that the sensor had good electrocatalytic activity for the reduction of H 2 O 2. The response time of the sensor is 5 s, and the linear detection range is 0.1 ~ 4.0 mM (R2 = 0.9991) with a low detection limit of 0.528 nM. Such sensor exhibited good long-term stability, and good anti-interfering ability from potential interfering species of glucose, ascorbic acid, dopamine, fructose and uric acid during the determination. This study thus provides a potential method to construct novel type of H 2 O 2 for practical application. [ABSTRACT FROM AUTHOR]

Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins. However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis. Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides. The introduction of cationic cellulose provides not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides. Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests. In addition, GO–DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g). Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples. This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics. Image 1 • A hydrophilic graphene oxide-dopamine-cationic cellulose composites were synthesized based on electrostatic interaction. • The composites were designed experience and the performance improvement of both the structure and charge. • The composites was exhibited high selectivity and sensitivity for glycopeptides enrichment. • The composites were effectively enriched in human serum, showing potential applications in complex biological samples. [ABSTRACT FROM AUTHOR]

• Hierarchically porous carbon networks (HPCN) were prepared through TMB-induced self-assembly and carbonization strategy. • The introduction of TMB results in changed morphology, enriched pore structure, and improved defect degree. • The O 2 − sensor HPCN/SPCE has the potential to distinguish between cancer and normal cells by detecting cell-released O 2 −. Realizing the quantitative detection of superoxide anions (O 2 −) is of great significance to the pathological research based on the correlation between O 2 − and many diseases. Currently, the main challenge for O 2 − electrochemical detection in the actual sample is the development of effective nano-mimetic materials to replace natural enzymes to achieve high-selectivity detection of O 2 −. In this work, hierarchically porous carbon networks (HPCN) were successfully prepared through 1,3,5-trimethylbenzene (TMB)-induced self-assembly and carbonization strategy. Owing to the introduction of TMB, HPCN obtains the changed morphology, enriched pore structure, and improved defect degree, which promotes mass transfer and leads to faster electron transfer efficiency. Therefore, the non-enzymatic O 2 − electrochemical sensor fabricated with HPCN (denoted as HPCN/SPCE) exhibits high sensitivity (607.4 μA cm−2 mM-1) and excellent selectivity for detecting O 2 −. Importantly, the sensor successfully achieved the dynamic monitor of O 2 − released from living cells and has the potential to distinguish between cancer and normal cells. [ABSTRACT FROM AUTHOR]

Glycosylation and phosphorylation are two of the most common and important post-translational modifications (PTMs) of proteins, which play critical roles in regulating a variety of complex biological processes and involvement in many diseases. Due to the low abundance of phosphopeptides and glycopeptides, highly selective enrichment methods are crucial to the identification of protein phosphorylation and glycosylation by mass spectrometry (MS). Here, monodisperse uniform Al3+-doping-TiO 2 mixed oxide microspheres were easily synthesized. The morphology was controlled by a sol-gel method, during the hydrothermal treatment. The obtained microspheres with uniform particle size distribution (about 1–2 μm)，high surface area and improved pore structures, were characterized by SEM, TEM, XRD and N 2 adsorption-desorption isotherms. Al3+-doping-TiO 2 was applied in enriching glycopeptides and phosphopeptides respectively or simultaneously by using different enrichment conditions, achieving selective enrichment of glycopeptides and phosphopeptides. 20 glycopeptides and 25 phosphopeptides enriched from the tryptic digest mixtures of human serum immunoglobulin G (IgG) and α-casein (molar ratio of 1:1) were obviously observed with greatly improved signal-to-noise (S/N) ratio. Meanwhile, the enrichment results of non-fat milk and human serum also show the enrichment selectivity from complex biological samples. This study will provide a novel insight for selective enrichment of glycopeptides and phosphopeptides in post-translational modification proteomics research. Image 1 • Monodisperse uniform Al3+-doping-TiO 2 microspheres with high surface area and improved pore structures were synthesized. • Al3+-doping-TiO 2 microspheres were exhibited high selectivity and sensitivity to phosphopeptide and glycopeptide enrichment. • Al3+-doping-TiO 2 microspheres can be used for glycopeptides and phosphopeptide enrichment simultaneously in one enrichment process. • Al3+-doping-TiO 2 microspheres can identify low-abundance phosphopeptides from complex biological samples. [ABSTRACT FROM AUTHOR]

• A simple modification method on carbon fiber microelectrodes (CFME) via in-situ reduction of AuAg bimetallic nanoparticles by polydopamine was proposed, and it offered a universal strategy to decorate novel metals onto microelectrode for different application in the future. • The bimetal synergistic effect enabled AuAg bimetallic decorated electrodes exhibited higher electrocatalytic activity (compared with Au and Ag monometallic decorated electrodes), showing an obvious enhancement toward H 2 O 2 sensing. • With a low detection limit (0.1 μM), the prepared 2Au1Ag-PDA/CFME was capable of detecting H 2 O 2 released from HepG2 living cells, indicating a potential usage of the fabricated electrode for H 2 O 2 detection in cancer cells. In this work, a facile in-situ reduction method was developed for the modification of carbon fiber microelectrode (CFME) to build novel electrochemical sensors for the detection of H 2 O 2. The polydopamine (PDA) was employed as the surface modification material for one-step decoration of AuAg bimetallic nanoparticles through in-situ reduction on the surface of PDA/CFME. Compared to Au-PDA/CFME and Ag-PDA/CFME, 2Au1Ag-PDA/CFME (immersed PDA/CFME in AgNO 3 for 1 h, HAuCl 4 •4H 2 O for 2 h in order) exhibited higher electrocatalytic activity toward H 2 O 2 sensing due to bimetal synergism. Under the optimal condition, the 2Au1Ag-PDA/CFME appeared a wide linear range of 0 μM - 55 μM (R2 = 0.990), 55 μM – 2775 μM (R2 = 0.991) with high sensitivity (12966 μA mM−1cm−2, 0–55 μM; 2534 μA mM−1 cm−2, 55–2775 μM), and low detection limit (0.12 μM). Furthermore, good selectivity and repeatability of 2Au1Ag-PDA/CFME favored its applications in biological samples, especially in cellular level. The detection of H 2 O 2 released from HepG2 living cells was realized by applying 2Au1Ag-PDA/CFME, indicating a potential usage of the fabricated electrode for H 2 O 2 detection in cancer cells. In addition, the above simple in-situ reduction method based on PDA's adhesion and reducibility offered a universal strategy to decorate noble metals onto microelectrode for different application in the future. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Developing nanomaterials as alternatives of enzymes is of great significance to realize qualification and quantitation of superoxide anion (O 2 −), which has been proved to play a crucial role in physiological condition. In this work, a novel electrochemical catalyst of cobalt nanoparticle doped porous cubic carbon (Co-PCC) was prepared through the calcination of zeolitic imidazolate framework-67 (ZIF-67), which was obtained from one-step synthesis. Then Co-PCC was used to construct enzyme-free electrochemical sensor for the detection of O 2 −. The response of H 2 O 2 , though much lower than that of O 2 −, was also caught by the Co-PCC/SPCE. The fabricated sensor exhibited obvious response towards O 2 − in the range of 0.8–76.8 μM (R2 = 0.997) with a high sensitivity of 3.59 × 10−4 mA μM−1 cm−2 and a limit of detection of 0.41 μM (S/N = 3). In addition, the proposed sensor can be used to detect O 2 − released from SK-BR-3 cells, which makes it possible to monitor the dynamic change of O 2 − in living cells. Unlabelled Image • Enzyme-free electrochemical sensor was developed for in-house electrochemical analysis. • A novel SOD-mimic nanozyme based on ZIF-67 was obtained from one-step synthesis. • The established sensor was used for electrochemical sensing of superoxide anions released from living cell. [ABSTRACT FROM AUTHOR]

The increased risk of breast cancer metastasis is closely linked to the effects of platelets. Our previously light-switchable diphtheria toxin A fragment (DTA) gene system, known as the LightOn system, has demonstrated significant therapeutic potential; it lacks antimetastatic capabilities. In this study, we devised an innovative system by combining cell membrane fusion liposomes (CML) loaded with the light-switchable transgene DTA (pDTA) and a ticagrelor (Tig) prodrug. This innovative system, named the sequential rocket-mode bioactivating drug delivery system (pDTA-Tig@CML), aims to achieve targeted pDTA delivery while concurrently inhibiting platelet activity through the sequential release of Tig triggered by reactive oxygen species with the tumor microenvironment. In vitro investigations have indicated that pDTA-Tig@CML, with its ability to sequentially release Tig and pDTA, effectively suppresses platelet activity, resulting in improved therapeutic outcomes and the mitigation of platelet driven metastasis in breast cancer. Furthermore, pDTA-Tig@CML exhibits enhanced tumor aggregation and successfully restrains tumor growth and metastasis. It also reduces the levels of ADP, ATP, TGF-β, and P-selectin both in vitro and in vivo, underscoring the advantages of combining the bioactivating Tig prodrug nanoplatform with the LightOn system. Consequently, pDTA-Tig@CML emerges as a promising light-switchable DTA transgene system, offering a novel bioactivating prodrug platform for breast cancer treatment.

Epidemiology shows that more than 6.8 million people in the world are influenced by inflammatory bowel disease (IBD) each year. IBD is a refractory inflammatory disease, and the disease mainly affects the colon. Shikonin (SK) was originally extracted from traditional Chinese medicine "Zicao" (with an English name Lithospermum erythrorhizon ) and found to inhibit inflammation, regulate immunity, and be involved in healing wounds. Herein, we used chitosan (CS), hyaluronic acid (HA), and pH-responsive polymer Eudragits S100 (ES100) to design SK-loaded ES100/HA/CS nanoparticles (SK@SAC) as an oral delivery system to treat the colitis mice. Particle size of SK@SAC was 190.3 nm and drug loading efficiency was 6.6%. SAC nanoparticles accumulated in RAW264.7 macrophages and exhibited colitis-targeted ability by increasing the local drug concentration as well as reducing nonspecific distribution after oral gavage. In TNBS-induced IBD mice, SK@SAC treatment had significant therapeutic effects, regulated of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10 and TGF-β), and also inhibited COX-2 and iNOS activity. SK@SAC also increased tight junction protein ZO-1 and occludin to some extent. These promising results showed that this novel oral SK-loaded nanoparticle drug delivery system for targeted treatment provides a new strategy for the management of IBD.

The detection of cancer biomarkers is of great significance for the early screening of cancer. Detecting the content of sarcosine in blood or urine has been considered to provide a basis for the diagnosis of prostate cancer. However, it still lacks simple, high-precision and wide-ranging sarcosine detection methods. In this work, a Ti 3 C 2 T X /Pt-Pd nanocomposite with high stability and excellent electrochemical performance has been synthesized by a facile one-step alcohol reduction and then used on a glassy carbon electrode (GCE) with sarcosine oxidase (SO x ) to form a sarcosine biosensor (GCE/Ti 3 C 2 T X /Pt-Pd/SO x ). The prominent electrocatalytic activity and biocompatibility of Ti 3 C 2 T X /Pt-Pd enable the SO x to be highly active and sensitive to sarcosine. Under the optimized conditions, the prepared biosensor has a wide linear detection range to sarcosine from 1 to 1000 µM with a low limit of detection of 0.16 µM (S/N = 3) and a sensitivity of 84.1 µA/mM cm 2 . Besides, the reliable response in serum samples shows its potential in the early diagnosis of prostate cancer. More importantly, the successful construction and application of the amperometric biosensor based on Ti 3 C 2 T X /Pt-Pd will provide a meaningful reference for detecting other cancer biomarkers., (© 2022 Wiley-VCH GmbH.)

Current cancer therapy has been restricted by the hypoxic microenvironment of tumors, especially for strongly oxygen-dependent photodynamic therapy. To defeat tumor hypoxia, an oxygen-irrelevant radical nanogenerator, PI/FBC , is developed by the co-assembly of iodized polymer PI and NIR photosensitizer FBC , and further evaluated as a remote controllable free radical generation platform for enhancing antitumor efficiency. The PI/FBC radical nanogenerator can be excited by NIR light to produce ROS through transfer of energy to oxygen and induce the formation of toxic iodine radicals via electron transfer to PI . Notably, unlike conventional tumor treatments, such a radical nanogenerator is controllable and insusceptible to oxygen concentration. Moreover, benefiting from the strong NIR emission of FBC , the distribution of the PI/FBC radical nanogenerator can be monitored without incorporating other imaging agents. This PI/FBC radical nanogenerator treatment will no doubt broaden the family of antitumor strategies by using non-oxygen radicals, which is significant for reference in the development of promising anticancer agents., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Protein glycosylation is among the most important post-translational modifications in living organisms and the research in the field of protein glycosylation continues to garner attention. Currently, the efficient separation and enrichment of glycoproteins and glycopeptides is the primary challenge of glycoproteomics research. The number of glycoproteins is small in complex biological samples. Moreover, the presence of highly-abundant, non-glycosylated, and modified peptides makes the detection of low-abundance glycopeptides more difficult. Therefore, efficient glycopeptide enrichment methods are required to improve the detection of these compounds. The development of highly selective glycopeptide enrichment tools is important to efficiently capture glycoproteins or glycopeptides at the molecular level. Compared with traditional glycopeptide-enriched materials, covalent organic framework materials have the advantages of large specific surface area and rich modification sites, thereby exhibiting great application potential in the field of glycopeptide enrichment. In this study, a novel covalent organic framework material (O-T-D-COFs) was prepared and applied for selective glycopeptide enrichment. We applied the solvothermal method, using 2,5-dimethoxy benzene-1,4-2 formaldehyde and 1,3,5-Tris(4-aminophenyl) benzene, to synthesize imino-based COFs. The Schiff base generated via copolymerization condensation reaction constitutes the framework of the material. Next, the synthesized intermediate material was oxidized to improve the enrichment performance of the material. The functional, specific glycopeptide-binding groups were modified on the COF channels and the structure of the material was characterized using scanning and transmission electron microscope, as well as infrared spectrum and solid-state nuclear magnetic resonance. The enrichment conditions comprised the loading and elution steps, including the optimization of the elution conditions. We could observe the clear profile of 32 glycopeptides derived from human serum immunoglobulin G (IgG) tryptic digests with a significantly improved signal-to-noise ( S/N ) ratio. We applied a complex sample system to verify the enrichment selectivity of the material when the molar ratios of the IgG and bovine serum albumin (BSA) tryptic digest mixtures reached 1∶50. In addition, we investigated the enrichment performance of the detection limit, enrichment capacity, recovery rate of the material, and the application potential in glycopeptides enrichment using real samples. The material showed a good detection limit (2.5 fmol/μL), an ideal enrichment capacity (120 mg/g), and enrichment recovery (103.5%±6.6% and 101.5%±10.4%). We identified a total of 86 glycopeptides derived from 53 glycoproteins with 94 N -glycosylation sites from only 1 μL human serum. The O-T-D-COFs exhibited a good glycopeptide separation and enrichment potential, indicating that the COF material has promising application potential in glycoproteomics.

Protein methylation is one of the most common and important post-translational modifications, and it plays vital roles in epigenetic regulation, signal transduction, and chromatin metabolism. However, due to the diversity of methylation forms, slight difference between methylated sites and nonmodified ones, and ultralow abundance, it is extraordinarily challenging to capture and separate methylated peptides from biological samples. Here, we introduce a simple and highly efficient method to separate methylated and nonmethylated peptides using 18-crown-6 as a mobile phase additive in high-performance liquid chromatography. Selective complexation between lysine and 18-crown-6 remarkably increases the retention of the peptides on a C18 stationary phase, leading to an excellent baseline separation between the lysine methylated and nonmethylated peptides. A possible binding mechanism is verified by nuclear magnetic resonance titration, biolayer interferometry technology, and quantum chemistry calculation. Through establishment of a simple enrichment methodology, a good selectivity is achieved and four methylated peptides with greatly improved signal-to-noise (S/N) ratios are successfully separated from a complex peptide sample containing 10-fold bovine serum albumin tryptic digests. By selecting rLys N as an enzyme to digest histone, methylation information in the histone could be well identified based on our enrichment method. This study will open an avenue and provide a novel insight for selective enrichment of lysine methylated peptides in post-translational modification proteomics.

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non-selective release of photosensitizers still exist. Herein, we report a 1 O 2 -responsive block copolymer (POEGMA-b-P(MAA-co-VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen ( 1 O 2 ) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1 O 2 -responsiveness of POEGMA-b-P(MAA-co-VSPpaMA) block copolymer enabled the realization of self-amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of fluorescent coumarin derivatives 2a - e were systematically designed, synthesized and studied for their Cu 2+ sensing performance in aqueous media. The sensitivities and selectivities of the on-to-off fluorescent Cu 2+ sensing signal were in direct correlation with the relative arrangements of the heteroatoms within the coordinating moieties of these coumarins. Probes 2b and 2d exhibited Cu 2+ concentration dependent and selective fluorescence quenching, with linear ranges of 0-80 μM and 0-10 μM, and limits of detection of 0.14 μM and 0.38 μM, respectively. Structural changes of 2b upon Cu 2+ coordination were followed by fluorescence titration, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), mass spectrometry, and single crystal X-ray diffraction on the isolated Cu 2+ -coumarin complex. The results revealed a 1:1 stoichiometry between 2b and Cu 2+ , and that the essential structural features for Cu 2+ -selective coordination are the coumarin C=O and a three-bond distance between the amide NH and heterocyclic N. Probe 2b was also used to determine copper (II) levels in aqueous soil extracts, with recovery rates over 80% when compared to the standard soil analysis method: inductively coupled plasma-mass spectrometry (ICP-MS)., Competing Interests: The authors declare no conflict of interest.

Aim: To determine whether the use of a mixed polymeric micelle delivery system based on vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/VES-grafted-chitosan (CS) mixed micelles (VES-g-CSO/VES-g-CS MM) enhances the delivery of C-DMSA, a theranostic fluorescent probe, for Hg 2+ detection and detoxification in vitro and in vivo., Methods: Mixed micelles self-assembled from two polymers, VES-g-CSO and VES-g-CS, were used to load C-DMSA and afforded C-DMSA@VES-g-CSO/VES-g-CS MM for cell and in vivo applications. Fluorescence microscopy was used to assess C-DMSA cellular uptake and Hg 2+ detection in L929 cells. C-DMSA@VES-g-CSO/VES-g-CS MM was then administered intravenously. Hg 2+ detection was assessed by fluorescence microscopy in terms of bio-distribution while detoxification efficacy in Hg 2+ -poisoned rat models was evaluated in terms of mercury contents in blood and in liver., Results: The C-DMSA loaded mixed micelles, C-DMSA@VES-g-CSO/VES-g-CS MM, significantly enhanced cellular uptake and detoxification efficacy of C-DMSA in Hg 2+ pretreated human L929 cells. Evidence from the reduction of liver coefficient, mercury contents in liver and blood, alanine transaminase and aspartate transaminase activities in Hg 2+ poisoned SD rats treated with the mixed micelles strongly supported that the micelles were effective for Hg 2+ detoxification in vivo. Furthermore, ex vivo fluorescence imaging experiments also supported enhanced Hg 2+ detection in rat liver., Conclusion: The mixed polymeric micelle delivery system could significantly enhance cell uptake and efficacy of a theranostic probe for Hg 2+ detection and detoxification treatment in vitro and in vivo. Moreover, this nanoparticle drug delivery system could achieve targeted detection and detoxification in liver., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Wei et al.)

The authors present a colorimetric method for the evaluation of the hydroxyl radical scavenging capability of antioxidants by exploiting carbon-confined mixed cobalt oxide nanoparticles (denoted as C-confined CoO x NPs) as a novel peroxidase mimic. The nanozyme can be prepared from the metal-organic framework ZIF-67 by calcination at a moderate temperature. It exhibits peroxidase-mimicking activity and catalyzes the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to form a blue product in the presence of H 2 O 2 via generation of hydroxyl radicals. However, in the presence of an antioxidant, the color reaction is suppressed due to scavenging of hydroxyl radicals by the antioxidant. Based on this principle, the hydroxy radical scavenging ability of glutathione (GSH), cysteine (Cys), tannic acid (TA) and tea polyphenols (TP) was assessed. It was found that these antioxidants can scavenge hydroxyl radicals in the following decreasing order: TA>Cys>GSH>TP. The assay was also used to quantify the antioxidative power of common fruit extracts. Graphical abstract Schematic presentation for evaluating the hydroxyl radical scavenging ability of different antioxidants using carbon-confined mixed cobalt oxide nanoparticles (denoted as C-confined CoO x NPs) as a highly active peroxidase mimic. With excellent activity, the C-confined CoO x NPs together with the visible peroxidase reaction can be employed as a powerful tool to rapidly screen appropriate antioxidants from natural samples and measure their activity for guiding their usage in related products.

Selective enrichment and sensitive detection of phosphopeptides are of great significance in many bioapplications. In this work, dendritic mesoporous silica nanoparticles modified with polydopamine and chelated Ti 4+ (denoted DMSNs@PDA-Ti 4+ ) were developed to improve the enrichment selectivity of phosphopeptides. The unique central-radial pore structures endowed DMSNs@PDA-Ti 4+ with a high surface area (362 m 2 g -1 ), a large pore volume (1.37 cm 3 g -1 ), and a high amount of chelated Ti 4+ (75 μg mg -1 ). Compared with conventional mesoporous silica-based materials with the same functionalization (denoted mSiO 2 @PDA-Ti 4+ ) and commercial TiO 2 , DMSNs@PDA-Ti 4+ showed better selectivity and a lower detection limit (0.2 fmol/μL). Moreover, 2422 unique phosphopeptides were identified from HeLa cell extracts with a high specificity (>95%) enabled by DMSNs@PDA-Ti 4+ , better than those in previous reports.

In this work, we fabricated a yolk-shell magnetic composite that contains mesoporous TiO 2 as the inner shell and flowerlike NiO as the outer shell (denoted as Fe 3 O 4 @H-TiO 2 @f-NiO) to reduce the limitations of single-component metal oxides in phosphopeptide enrichment. The NiO nanosheets play a synergistic role in phosphopeptide enrichment. And the unique flowerlike structure of NiO with sufficient space can facilitate the reversible insertion/extraction of peptides, which will have less impact on the enrichment process of the inner TiO 2 shell. The yolk-shell structure and two types of porous nanostructures endowed this composite with a high surface area (156.58 m 2 g -1 ) and a large pore volume (0.37 cm 3 g -1 ). Owing to the high surface area and combined properties of TiO 2 and NiO, the Fe 3 O 4 @H-TiO 2 @f-NiO microspheres showed a better performance for phosphopeptide enrichment than the same material without NiO nanosheets (Fe 3 O 4 @H-TiO 2 ). According to the LC-MS/MS results, 972 unique phosphopeptides were identified from HeLa cell extracts with a high selectivity (91.9%) by Fe 3 O 4 @H-TiO 2 @f-NiO relative to 837 phosphopeptides (selectivity: 60.2%) by Fe 3 O 4 @H-TiO 2 . The results demonstrated that, compared with single-component metal oxides, composite metal oxides could enhance the selectivity and sensitivity for phosphopeptide enrichment.

Here, the combination of Nafion with microporous hollow carbon spheres (MHCS) is first proposed to fabricate a disposable metal-free electrode for heavy metal stripping sensing. The MHCS-Nafion composite film electrode is prepared by drop-casting a mixture of MHCS and Nafion onto the lab-made screen-printed carbon electrode (SPCE(*)). Results demonstrate that the interfusion of MHCS into Nafion offers enhanced performance for the electro-enrichment and stripping of lead and cadmium over the only Nafion film: 1) abundant MHCS immobilized on the electrode surface serve as effective nucleation sites for metal ion reduction; 2) the mixing of MHCS into Nafion enlarges the active surface of negative-charged Nafion for the electrostatic adsorption of metal cations. The proposed MHCS-Nafion/SPCE(*) provides linear responses for Pb(2+) and Cd(2+) in the range of 2 - 200 μg/L, with a detection limit of 1.37 and 1.63 μg/L, respectively. Practical applications of the sensor in water sample detection with good accuracy have also been confirmed.

In order to get high water solubility, monodisperse, superparamagnetic nanoparticles, poly (acrylic acid) was employed to modify Fe3O4 by a high-temperature solution-phase hydrolysis approach. Then, folic acid (FA) and fluorescein isothiocyanate were successively conjugated with prepared magnetic nanoparticles (MNPs). The functional MNPs were characterized by X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscope (TEM), inductively coupled plasma-atomic emission spectrometer (ICP-AES), and vibrating sample magnetometer (VSM), respectively. The toxicity of the materials was evaluated by selecting NIH/3T3 fibroblast cells and no toxic effect was observed. The fluorescent imaging and targeting property of the MNPs were also realized in vitro and in vivo experiments by confocal laser scanning microscopy (CLSM) and Kodak In-Vivo FX Professional Imaging System, respectively. The results indicated that the final products exhibited interesting magnetic, optical and targeting properties for further potential applications in biological and biomedical fields.

4-anilinoquinazoline and 4-anilinoquinoline scaffolds bearing a 2,2,6,6-tetramethylpiperidine-N-oxyl(TEMPO) have been synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and A431 cell lines. Compared to their corresponding parent compounds, all of the new compounds bearing a TEMPO showed more efficient inhibition for EGFR and A431 cells. Furthermore, we have proved that these molecules bearing a TEMPO can exactly get into A431 cells exerting inhibitory effect that may be used for EPR detecting. In our docking model, quinazolines bearing a TEMPO on either 6- or 3-positions took different linking modes according to EGFR crystal structure. In contrast to their parent compounds, these new TEMPO-derived analogues possessed compatible inhibitory effect that might be useful as potential EGFR inhibitors and as EPR bio-probes., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In this study, the size-uniform (5-6 nm), nearly spherical, and well-dispersed aqueous Fe3o4 magnetic nanoparticles were prepared by an improved chemical coprecipitation method. The DDAT-terminated (S-1-Dodecyl-S'-(alpha,alpha'-dimethyl-alpha"-acetic acid) trithiocarbonate) polymethacrylic (PMA-DDAT) was chosen as the apt surfactant, and the terminal DDAT can be used as a high efficient RAFT chain-transfer agent for further functionalization. Then, the functionalized Fe3O4 reacted with 4-amino-2,2,6,6-tetramethyl-piperidine-oxyl (4-NH2-TEMPO) to give the spin labeling magnetic nanoparticles. Finally, the multifunctional MNPs was characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), electron paramagnetic resonance (EPR), Fourier transform infrared spectrometer (FT-IR), and vibrating-sample magnetometer (VSM). The obtained highly water-soluble, superparamagnetic, and multifunctional magnetic nanoparticles should find potential applications in biomedical research.

Mercury is a highly toxic metal that can cause significant harm to humans and aquatic ecosystems. This paper describes a novel approach for mercury (Hg(2+)) ion detection by using label-free oligonucleotide probes and Escherichia coli exonuclease I (Exo I) in a microfluidic electrophoretic separated platform. Two single-stranded DNAs (ssDNA) TT-21 and TT-44 with 7 Thymine-Thymine mispairs are employed to capture mercury ions. Due to the coordination structure of T-Hg(2+)-T, these ssDNAs are folded into hairpin-like double-stranded DNAs (dsDNA) which are more difficult to be digested by Exo I, as confirmed by polyacrylamide gel electrophoresis (PAGE) analysis. A series of microfluidic capillary electrophoretic separation studies are carried out to investigate the effect of Exo I and mercury ion concentrations on the detected fluorescence intensity. This method has demonstrated a high sensitivity of mercury ion detection with the limit of detection around 15 nM or 3 ppb. An excellent selectivity of the probe for mercury ions over five interference ions Fe(3+), Cd(2+), Pb(2+), Cu(2+) and Ca(2+) is also revealed. This method could potentially be used for mercury ion detection with high sensitivity and reliability., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A series of 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-substituted-phenoxy)pyrimidine derivatives were elaborately designed based on the skeleton of Lapatinib, and evaluated for their potential to inhibit epidermal growth factor receptor (EGFR) and ErbB-2 tyrosine kinase activities and antiproliferative activities against A431 and SKOV-3 cell lines. Among these synthesized pyrimidine derivatives, 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-acrylamidophenoxy)pyrimidine (6), 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-cyanoacetamidophenoxy)pyrimidine (9), 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-{3-[6-(4-amino)pyrimidinyl]amino) phenoxy}pyrimidine (11) and 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-phenoxyacetamidophenoxy)pyrimidine (14) could significantly inhibit dual EGFR/ErbB-2 kinase activities (IC(50)=37/29 nM, 48/38 nM, 61/42 nM, 65/79 nM, respectively). And compounds 6 and 11 also showed the most potent antiproliferative activities in vitro, with the IC(50) value of 6 being 3.25 μM for A431 and 0.89 μM for SKOV-3, as for 11, 4.24 μM for A431 and 0.71 μM for SKOV-3, respectively. Docking study was also performed to determine the possible binding model., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Neurotoxicity was investigated in nano-SiO2-treated cultured PC12 cells, an in vitro neuronal cell model, in order to define a relatively safe dose range for its application. The following were observed in the present study: (1) A dose-dependent increase in the level of reactive oxygen species (ROS) with a corresponding decrease in the level of glutathione (R2=0.965) suggesting 20- and 50-nm SiO2-induced free radical generation and glutathione depletion. (2) A dose- and time-dependent decrease in cell viability that was associated with elevation of ROS level, especially after 24-h nano-SiO2 exposure (R2=0.965), suggesting the role of oxidative stress on nano-SiO2 induced cell death. (3) An increase in the level of thiobarbituric-acid reactive species that correlated reversely with cell viability of the PC12 cells treated with nano-SiO2 (R2=0.945) suggesting nano-SiO2-induced membrane damage caused by lipid peroxidation. (4) A dose-dependent increase in sub-G1 population in SiO2-exposed cells along with cell shrinkage and nuclear condensation from morphological examination suggesting nano-SiO2-induced cell apoptosis. Furthermore, nano-SiO2 exposure diminished the ability of neurite extension in response to nerve growth factor in treated PC12 cells. In summary, SiO2 nanoparticle exposure resulted in dose-dependent neurotoxicity in cultured PC12 cells that was probably associated with oxidative stress and induced apoptosis., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

The fabrication of a new amphiphilic block copolymer composed of a poly DL-lactic acid (PLA) hydrophobic backbone and pH dependent thermo-sensitive poly (N-isopropyl) methacrylamide-co-N-isopropylmaleamic acid-co-10-undecenoic acid (PNIPAAm-co-NIPMMA-co-UA) entities as hydrophilic domains as well as carrying 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) residues for electron spin resonance (ESR) labeling is reported. The lower critical solution temperature (LCST) of the copolymer was determined by optical absorbance measurements. The LCST was pH dependent and varied in a narrow practical range, 35.4 °C at pH 5.0, 37.5 °C at pH 6.5 and 39.4 °C at pH 7.4, which was below, near and above nominal physiological temperature respectively. The assembly of the copolymer into micelles in aqueous solution at temperatures below the LCST was confirmed by FT-IR, (1)H NMR and fluorescence spectroscopy. It is demonstrated that the anticancer drug, 5-fluorouracil (5-FU) can be loaded effectively within the polymeric micelles and released in response to environmental stimuli- namely, pH and temperature., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

A green fluorescent protein chromophore inspired chemosenor for Zn(2+) was designed and synthesized. A Zn(2+) specific fluorescence enhancement was observed due to restricted rotation between the 1,10-phenanthroline and imidazolone moieties., (© The Royal Society of Chemistry 2011)

Aims: In this article we report our recent developments in the field of electron paramagnetic resonance oximetry., Materials & Methods: Novel synthesized ferrocenyl nitroxide radicals (FcN)-1-6 were evaluated to determine their electron paramagnetic resonance oxygen responsiveness and reduction resistance. The 3-ferrocenyl-N-(oxyl-2,2,6,6-tetramethylpiperidin-4-yl) butanamide radical (FcN-6), with outstanding electron paramagnetic resonance oxygen sensitivity, was encapsulated in Pluronic F-127 polymeric nanoparticles., Results: The nanoparticles exhibited good oxygen sensitivity, long-term stability of responsiveness, targeting to lung, liver and tumor, and low toxicity., Conclusion: These features make this novel nanoparticle especially valuable for mapping O₂ concentrations in the body and monitoring the oxygen level inside tissues.

Integrating the advantages of screen printing technology with the encouraging electroanalytical characteristic of metallic bismuth, we developed an ultrasensitive and disposable screen-printed bismuth electrode (SPBE) modified with multi-walled carbon nanotubes (MWCNTs) for electrochemical stripping measurements. Metallic bismuth powders and MWCNTs were homogeneously mixed with graphite-carbon ink to mass-prepare screen-printed bismuth electrode doped with multi-walled carbon nanotubes (SPBE/MWCNT). The electroanalytical performance of the prepared SPBE/MWCNT was intensively evaluated by measuring trace Hg(II) with square-wave anodic stripping voltammetry (SWASV). The results indicated that the SPBE modified with 2 wt% MWCNTs could offer a more sensitive response to trace Hg(II) than the bare SPBE. The stripping current obtained at SPBE/MWCNT was linear with Hg(II) concentration in the range from 0.2 to 40 µg/L (R(2) = 0.9976), with a detection limit of 0.09 µg/L (S/N = 3) under 180 s accumulation. The proposed "mercury-free" electrode, with extremely simple preparation and ultrahigh sensitivity, holds wide application prospects in both environmental and industrial monitoring., (2011 © The Japan Society for Analytical Chemistry)

Nanoparticles such as nano-SiO(2) are increasingly used in food, cosmetics, diagnosis, imaging and drug delivery. However, toxicological data of nano-SiO(2) on hepatic cells in vitro and their detailed molecular mechanisms still remain unclear. In order to assess toxicity of nano-SiO(2), L-02 cells were exposed to 0.2, 0.4 and 0.6 mg/ml of SiO(2) colloids (21, 48 and 86 nm) for 12, 24, 36 and 48h. Lactate dehydrogenase released from damaged cells were quantified, cellular ultrastructural organization was observed, and the levels of reactive oxygen species (ROS), lipid peroxidation and glutathione were measured. Apoptosis induced by 21 nm SiO(2) was characterized by annexin V-FITC/PI staining and DNA ladder assay. Furthermore, apoptosis related proteins such as p53, Bax and Bcl-2 were analyzed by using western blot analysis. Our data indicated that nano-SiO(2) caused cytotoxicity in size, dose and time dependent manners. Oxidative stress and apoptosis were induced by exposure to 21 nm SiO(2). Moreover, the expression of p53 and Bax was increased in time and dose dependent patterns, whereas the expression of Bcl-2 was not significantly changed. In conclusion, ROS-mediated oxidative stress, the activation of p53 and up-regulation of Bax/Bcl-2 ratio are involved in mechanistic pathways of 21 nm SiO(2) induced apoptosis in L-02 cells., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

A series of spin-labeled melphalan and chlorambucil derivatives, coupling the alkylating agents with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) radicals, were synthesized, characterized, and their biological properties in vitro were evaluated. These compounds showed much higher cytotoxic activity against human leukemia cell line K562 in vitro than their parent compounds.

In the present study, toxicities of silica nanoparticles with sizes of 21 and 48nm were assessed in myocardial H9c2(2-1) cells using the methylthiazolyldiphenyl-tetrazolium bromide reduction and lactate dehydrogenase assays. Cell injuries were characterized by morphological changes using hematoxylin and eosin staining. Reactive oxygen species, malondialdehyde and glutathione were measured to evaluate the levels of oxidative stress. To elucidate mechanisms, cell cycle distributions and the expressions of p53, p21 and Bax were also analyzed. Results showed that silica nanoparticles produced cytotoxicities in size, dose (0.1-1.6mg/ml) and time (12, 24, 36 and 48h exposure) dependent manners. Moreover, the particles caused oxidative stress, induced G1 phase arrest and upregulated levels of p53 and p21. Taken together, these data suggested that cell injuries were triggered by the generation of oxidative stress; p53 and p21 mediated G1 phase arrest is a potential mechanistic pathway of silica nanoparticles induced damage in H9c2(2-1) cells., (Copyright © 2009 Elsevier B.V. All rights reserved.)

The effects of the addition of three different organosiloxanes, 3-aminopropyltrimethoxysilane (APTMS), 3-aminopropyltriethoxysilane (APTES) and 3-mercaptopropyltrimethoxysilane (MPTMS), on the phase behavior and the pore size of the surfactant-extracted materials have been investigated using powder XRD, TEM, Nitrogen adsorption/desorption isotherms and elemental analysis. The organosiloxanes were added to a typical synthesis, which results in a KIT-6 type in the absence of organosiloxanes. Their addition resulted in mesophase transformation or not, depending on the nature of functional groups of organosiloxanes. Increasing the content of APTMS or APTES in the silica sources not only led to the transformation of mesostructures from cubic bicontinuous Ia-3d to mixed mesostructure then towards two-dimensional (2-D) hexagonal p6mm and eventually to disordered structure, but also caused an increase of the pore size. However, the d spacing and the pore size of the cubic bicontinuous Ia-3d mesoporous solids can be decreased by addition of MPTMS between 0 and 2.5 mol% in the silica sources without a distinct decrease in the long-range order of the material. These results are discussed in terms of differences in the ability of the organosiloxanes to interact with the surfactant P123. The potential applications of these mesoporous materials are supports for the immobilization of enzymes, heavy metal sorbents, base catalysts, etc.

In order to elucidate the nanoparticle-induced cytotoxicity and its mechanism, the effects of 20 and 50 nm silica nanoparticles on cultured human embryonic kidney (HEK293) cells were investigated. Cell viability, mitochondrial function, cell morphology, reactive oxygen species (ROS), glutathione (GSH), thiobarbituric acid reactive substance (TBARS), cell cycle and apoptosis were assessed under control and silica exposed conditions. Exposure to 20 or 50 nm SiO(2) nanoparticles at dosage levels between 20 and 100 microg/ml decreased cell viability in a dose-dependent manner. Median lethal dose (LD(50)) of 24h exposure was 80.2+/-6.4 and 140.3+/-8.6 microg/ml for 20 and 50 nm SiO(2) nanoparticles, respectively. Morphological examination revealed cell shrinkage and nuclear condensation after SiO(2) nanoparticle exposure. Increase in intracellular ROS level and reduction in GSH content were also observed in SiO(2) nanoparticle-exposed HEK293 cells. Increase in the amount of TBARS suggested an elevated level of lipid peroxidation. Flow cytometric analysis showed that SiO(2) nanoparticles can cause G2/M phase arrest and apoptotic sub-G1 population increase in a dose-dependent manner. In summary, exposure to SiO(2) nanoparticles resulted in a dose-dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.

The direct electron transfer of glucose oxidase (GOx) immobilized on a large-pore mesoporous silica KIT-6 matrix fixed to a screen-printed electrode (SPE) and its application as a disposable biosensor were studied. KIT-6 plays a vital role in this method through immobilizing GOx and facilitating the electron communication between the active centers of GOx and the surface of the SPE. GOx immobilized on KIT-6 maintains its bioactivity and structure and displays stable and well-defined redox peaks with a formal potential of -428 mV (vs. Saturated Calomel Electrode), with a heterogeneous electron transfer rate constant of 4.15 s(-1) in phosphate buffer (0.05 M, pH 6.0). Upon the addition of glucose into air-saturated phosphate buffer solution, the reduction peak current decreases, which can be used analytically for glucose detection. The biosensor exhibits a linear response to glucose concentration ranging from 0 to 2.83 mM and a sensitivity of 7.29 microA (mM)(-1) cm(-2) at an applied potential of -0.5 V. The present work provides a promising strategy for fabricating a novel and disposable mediator-free glucose biosensor, which could be potentially mass-produced through further development.

New electron paramagnetic resonance (EPR) oximetry probes were identified in the class of carbon black materials. These compounds exhibit very high oxygen sensitivity and favorable EPR characteristics for biological applications. At low pO(2), the linewidth is particularly sensitive to changes in oxygen tension (sensitivity of 750 mG/mmHg). The application of the probes for oximetry was demonstrated in vivo: the pO(2) was measured in muscle in which the blood flow was temporarily restricted as well as in tumor-bearing mice during a carbogen breathing challenge. The responsiveness to pO(2) was stable in muscle for at least 3 months. No toxicity was observed using these materials in cellular experiments and in histological studies performed 2, 7, and 28 days after implantation. In view of their EPR characteristics (high sensitivity) as well as the well-characterized production procedure that make them available on a large scale, these probes can be considered as very promising tools for future developments in EPR oximetry., (Copyright 2004 Wiley-Liss, Inc.)