Construction of self-enhanced photoelectrochemical platform for L-cysteine detection via electron donor-acceptor type coumarin 545 aggregates.

Self-enhanced electron donor-acceptor type coumarin 545 aggregates prepared via an anionic surfactant-assisted reprecipitation method provide an underlying approach for the photoelectrochemical detection of L-cysteine, which can be employed in aqueous solution without the addition of electron donors.

Ultrasensitive dual-quenching electrochemiluminescence immunosensor for prostate specific antigen detection based on graphitic carbon nitride quantum dots as an emitter.

Early monitoring of prostate-specific antigen (PSA) is crucial in diagnosis and proactive treatment of prostate disease. Herein, a dual-quenching ternary ECL immunosensor was designed for PSA detection based on graphitic carbon nitride quantum dots (g-CNQDs, as an emitter), potassium persulfate (K2S2O8, as a coreactant), and silver nanoparticles doped multilayer Ti3C2 MXene hybrids (Ag@TCM, as a coreaction accelerator). First, Ag@TCM was immobilized on the surface of a glassy carbon electrode, then g-CNQDs was further adsorbed on Ag@TCM to acquire a higher initial ECL signal at a potential window from - 1.3 to 0.0 V (vs. Ag/AgCl). Ag@TCM not only acted as the coreaction accelerator, but also as a matrix to load enormous g-CNQDs and prostate-specific capture antibody via Ag-N bond. Meanwhile, prostate-specific detection antibody was marked by gold nanoparticles modified manganese dioxide as a dual-quenching probe (Ab2- Au@MnO2). When Ab2-Au@MnO2 was introduced into the ternary ECL system via sandwiched immuno-reaction, the high-sensitive detection of PSA was achieved by the dual-quenching effect, caused by the resonant energy transfer from g-CNQDs (energy donor) to Au@MnO2 (energy acceptor). As a result, this ECL immunosensor showed a good dynamic concentration range from 10 fg·mL-1 to 100 ng·mL-1 with a detection limit of 6.9 fg·mL-1 for PSA detection. The dual-quenching ECL strategy presented high stability and good specificity to open up a new pathway for ultrasensitive immunoassay.

Novel Enhanced Lanthanide Electrochemiluminescence Luminophores: Ce3+-Doped TbPO4 Facile Synthesis and Detection for Mucin1.

Despite the upsurging interest in electrochemiluminescence (ECL) of lanthanides, the research in this field is still in its infancy due to the low intensity. In this work, a series of Ce3+-doped terbium orthophosphates (TbPO4:Ce) in different proportions have been synthesized through the co-precipitation method at room temperature. Meanwhile, through the investigation of morphologies and ECL properties of these TbPO4:Ce, it is concluded that the ECL intensity reaches the maximum when the molar ratio of Tb/Ce is 9:1 and the material is nanorod-shaped. The ECL intensity of TbPO4:Ce is significantly improved by doping with Ce3+ due to the dual sensitization strategy of the antenna effect from PO43- to Tb3+ and the energy transfer from Ce3+ to Tb3+. Interestingly, doping with Ce3+ can not only adjust morphology of TbPO4:Ce but also improve the ECL intensity. In addition, to verify the application of TbPO4:Ce, two single mucin1 (MUC1) aptamers are linked together to form a dual MUC1 aptamer chain. Then, a simple and sensitive ECL biosensor is constructed for the detection of MUC1, which can recognize the double amount of MUC1 and quench the ECL signal. As expected, the proposed biosensor shows good stability and acceptable selectivity and achieves sensitive detection of MUC1 with a dynamic range from 1 fg·mL-1 to 10 ng·mL-1 and a limit of detection of 0.5 fg·mL-1. This work may pave a new avenue for the study of direct ECL emission of lanthanides and prove to be ideal for the research of new ECL luminophores in electrochemical analysis.

Functionalized europium-porphyrin coordination polymer: Rational design of high performance electrochemiluminescence emitter for mucin 1 sensing.

The excellent characteristics of porphyrins have inspired widespread interest in electrochemiluminescence (ECL). However, the limited ECL intensity and poor stability of porphyrins in aqueous solution are still severely restricted further biological application. Here, we subtly synthesized a functionalized europium and 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) coordination polymer (Eu-PCP) by a one-step solvothermal method. In sharp contrast to the pristine TCPP, Eu-PCP showed a higher and more stable ECL red-light emission (673 nm) at low potential (-1.1 V, vs Ag/AgCl), which was 7.7-fold higher ECL intensity and 4.6-fold efficiency. In view of the crucial role of mucin 1 (MUC1) in tumor overexpression, it was selected as the target molecule. Combined with exonuclease III (Exo III)-assisted recycling amplification strategy, a ternary ECL biosensor was constructed for the MUC1 detection based on Eu-PCP as a satisfied ECL emitter, gold nanoparticles capped CeO2 (CeO2@Au) as the coreactant accelerator and peroxydisulfate as coreactant. Meanwhile, gold nanoparticles capped MnO2 (MnO2@Au) was used as the quenching probe to achieve a highly sensitive detection of MUC1. The proposed biosensor exhibited a wide linear range from 1 fg mL-1 to 10 ng mL-1 with a low limit of detection (0.32 fg mL-1). By changing the corresponding target recognition DNA, this strategy could be expanded to detect other biomarkers.

Determination of ascorbic acid using electrochemiluminescence sensor based on nitrogen and sulfur doping graphene quantum dots with luminol as internal standard.

A novel internal standard electrochemiluminescence (ECL) sensor has been designed for the detection of ascorbic acid (AA). The adopted dual-emission luminophore (NSGQDs-PEI-luminol-Pt) is composed of nitrogen and sulfur double-doped graphene quantum dots (NSGQDs, as the main luminophore), luminol (as the auxiliary luminophore and internal standard), platinum nanoparticles (Pt NPs, as the co-reaction accelerator), and polyetherimide (PEI, as the linker of NSGQDs and luminol). The results suggest obviously enhanced  ECL intensities by the Förster resonance energy transfer (FRET) between luminol (donor) and NSGQDs (acceptor). In this sensing system, the cathodic ECL intensities of NSGQDs (ECL-1, -1.8 V vs. Ag/AgCl) gradually decrease with increasing concentration of AA, while the anodic ECL intensities of luminol (ECL-2, 0.3 V vs. Ag/AgCl) almost remain essentially constant at a potential window from -2.0 to 0.4 V. The natural logarithm of the ratio between ECL-1 and ECL-2 (ln I (ECL-1/ECL-2)) shows a good linear relationship with AA concentration ranging from 10 to 360 nM. The regression equation is ln I (ECL-1/ECL-2) = - 0.0059 cAA + 3.55 (R2 = 0.992) with a limit of detection of 3.3 nM. Such sensor has also been applied for monitoring AA in human serum. The recovery range was 96.5-105.3% and the relative standard deviation was  1.3-3.3%.

A Superstable Luminescent Lanthanide Metal Organic Gel Utilized in an Electrochemiluminescence Sensor for Epinephrine Detection with a Narrow Potential Sweep Range.

Metal organic gels (MOGs) as a new type of porous soft-hybrid supramolecular material have attracted widespread interest in various aspects due to their unique optical properties. In this work, we report a novel electrochemiluminescence (ECL) emission (679 nm) lanthanide MOG, which has been synthesized by a simple and rapid method at room temperature. This MOG (Tb-Ru-MOG) consists of a central metal ion, terbium (III), and two different ligands, tris(4,4'-dicarboxylicacid-2,2'-bipyridyl) ruthenium (II) dichloride (Ru(dcbpy)32+) and 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine (Hcptpy). Compared with the classic system of tris(2,2'-bipyridyl) ruthenium (II) dichloride (Ru(bpy)32+)/S2O82-, Tb-Ru-MOG/S2O82- owns a narrower potential sweep range (0.00 to -0.85 V) and a more stable and stronger ECL signal. Interestingly, the ECL intensity only decreased 2.0 and 0.1% after continuous scanning for 8000 s and storing at room temperature for 3 months. The possible ECL mechanism has been discussed in detail, which is mainly attributed to the internal synergies (antenna effect and energy transfer) and external co-reactant. Inspired by the unique luminescence characteristics of Tb-Ru-MOG, the application in electroanalytical chemistry was identified by the ECL on-off response for epinephrine with a linear range from 1.0 × 10-10 to 1.0 × 10-3 mol·L-1 and a detection limit of 5.2 × 10-11 mol·L-1. The results suggest that the as-proposed Tb-Ru-MOG will provide a robust pathway for new ECL luminophores in analysis.

Nitrogen-doped graphene quantum dots coated with gold nanoparticles for electrochemiluminescent glucose detection using enzymatically generated hydrogen peroxide as a quencher.

Nitrogen-doped graphene quantum dots (N-GQDs) were prepared from dicyandiamide and then used as both an electrochemiluminescence (ECL) emitter and a reductant to produce gold nanoparticles (Au-N-GQDs) on their surface without using any reagent. In order to avoid resonance energy transfer, the Au-N-GQDs were stabilized with chitosan. Transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), UV-vis spectroscopy (UV-vis) and ECL methods were used to characterize the nanocomposite. The materials was placed on a glassy carbon electrode (GCE), and the ECL signals are found to be strongly quenched by hydrogen peroxide that is enzymatically produced by oxidation of glucose. With the applied typical potential of -1.7 V, the ECL of the Au-N-GQDs modified GCE decreases linearly in the 10 nM to 5.0 µM glucose concentration range, and the lower detection limit is 3.3 nM. The influence of H2O2 to the signal has been discussed and a possible mechanism has been presented. Graphical abstract Schematic presentation of the reduction of gold nanoparticles with nitrogen-droped graphene quantum dots (N-GQDs) to form Au-N-GQDs. They were used to detect glucose by electrochemiluminescence through a signal off strategy.

Biflavones from Ginkgo biloba as novel pancreatic lipase inhibitors: Inhibition potentials and mechanism.

Reduction of lipid absorption has been recognized as an attractive approach for the discovery of new drugs to treat obesity and overweight. The leave extract of Ginkgo biloba has been widely used for the treatment of metabolic diseases (such as hyperlipidemia) in both eastern and western countries, but the bioactive compounds in Ginkgo biloba and the underlying mechanism have not been fully characterized. This study aimed to investigate the inhibition potentials and mechanism of major biflavones from G. biloba on pancreatic lipase (PL), a key target regulating lipid absorption. The results clearly demonstrated that all tested biflavones in G. biloba including isoginkgetin, bilobetin, ginkgetin and sciadopitysin, displayed strong to moderate inhibitory effects on PL with the IC50 values ranging from 2.90 µM to 12.78 µM. Further investigations on both inhibition kinetic analyses and docking simulations demonstrated that isoginkgetin, bilobetin and ginkgetin were potent PL inhibitors (Ki < 2.5 µM), which could create strong interactions with the catalytic triad of PL via hydrogen bonding. These findings provided a new powerful evidence for explaining the hypolipidemic effects of G. biloba, while these newly identified PL inhibitors from G. biloba could serve as lead compounds for the development of biflavonoid-type PL inhibitors.

Detection of CD22 Expression in Living Cancer Cells by Semiconductor Quantum Dots.

CD22 is an important drug target for the treatment of autoimmune diseases and B cell-derived malignancies. In this study, N-acetylneuraminic acid functionalized quantum dots nanoconjugate was synthesized and used for targeting and fluorescence imaging of CD22 on living cells. The nanoprobe was prepared by conjugating N-acetylneuraminic acid (NANA) on the carboxyl groups modified CdSe/ZnS quantum dots (COOH-QDs) via NHS/EDC mediated esterification. The NANA-QDs nanoprobe showed excellent size distribution, very low cytotoxicity and super fluorescent properties for biological imaging applications. The specificity of NANA-QDs nanoparticles for CD22 on living cancer cells was validated by cellular uptake inhibition assays, colocalization of the immunofluorescence staining with both anti-CD22 antibody and NANA-QDs nanoparticles. Furthermore, CD22 mediated endocytosis of NANA-QDs nanoparticles was investigated by cellular internalization kinetics in Daudi cells at multiple time points. The newly developed NANA-QDs based assay was successfully used to determine the expression levels of CD22 on various cancer cells, which were highly consistent with the results determined by immunofluorescence staining assay and western blotting. All these findings demonstrated that NANA-QDs nanoparticles system was a practical fluorescent nanoprobe for bioimaging of CD22, which held great promise in a wide variety of biomedical applications of CD22 related studies.

Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2.

Human carboxylesterases (hCEs) are key enzymes from the serine hydrolase superfamily. Among all identified hCEs, human carboxylesterase 2 (hCE2) plays crucial roles in the metabolic activation of ester drugs including irinotecan and flutamide. Selective and potent hCE2 inhibitors could be used to alleviate the toxicity induced by hCE2-substrate drugs. In this study, more than fifty flavonoids were collected to assay their inhibitory effects against hCE2 using a fluorescence-based method. The results demonstrated that C3 and C6 hydroxy groups were essential for hCE2 inhibition, while O-glycosylation or C-glycosylation would lead to the loss of hCE2 inhibition. Among all tested flavonoids, 5,6-dihydroxyflavone displayed the most potent inhibitory effect against hCE2 with the IC50 value of 3.50 µM. The inhibition mechanism of 5,6-dihydroxyflavone was further investigated by both experimental and docking simulations. All these findings are very helpful for the medicinal chemists to design and develop more potent and highly selective flavonoid-type hCE2 inhibitors.