Jinxu Qi

Gold nanoparticles superlattices assembly for electrochemical biosensor detection of microRNA-21

Gold nanoparticles (AuNPs) superlattice and small molecule dyes such as toluidine blue have remarkable effect on signal amplification. In this report, a label-free and simple electrochemical microRNA biosensor is developed by employing toluidine blue (TB) as a redox indicator and AuNPs superlattice as a support material. Conductive polymer, polypyrrole coated AuNPs was self-assembled to form a superlattice which exhibited the most close-packed type thereby producing the maximum current. The successful immobilization of the single strand RNA (ss-RNA) probe and hybridization with the target microRNA sequence were confirmed by electrochemical cyclic voltammetry (CV) methods as well as differential pulse voltammetry (DPV) technique, which was used to determine the oxidation peak current of TB under optimal condition. TB with efficient signal amplification was applied in microRNA biosensor for the first time. By employing this strategy, microRNA can be detected in a range from 100aM to 1nM with a relatively low detection limit of 78aM. Alongside the outstanding sensitivity and selectivity, this nanobiosensor had great reproducibility and showed a remarkable response in the real sample analysis with serum samples. In conclusion, the proposed electrochemical nanobiosensor could be clinically useful in the early detection of the breast cancer by direct detection of the serum microRNA-21 in real clinical samples without sample preparation, RNA extraction and/or amplification.

Synthesis, crystal structure and antiproliferative mechanisms of 2-acetylpyridine-thiosemicarbazones Ga(III) with a greater selectivity against tumor cells

Thiosemicarbazone Ga(III) complexes (C3-C5) were synthesized and characterized by X-ray single crystal diffraction, and they were all 1:1 ligand/Ga(III) complexes. The antiproliferative activity of these Ga(III) complexes was tested against three cancer cell lines, demonstrating that Ga(III) complexes showed about 3-10 folds more anticancer activity than their ligands alone. Importantly, thiosemicarbazones and Ga(III) complexes have a low toxicity to human fetal lung fibroblast cells (MRC-5) and exhibit a high therapeutic index for tumor cells. The results of UV-visible spectroscopy showed that the binding constant of C4 with Topo-I-DNA was significantly higher than that of L4. The Ga(III) complex (C4) caused Topo-I inhibition and distinct DNA cleavage. Moreover, Ga(III) complex and thiosemicarbazone ligand prolonged the G1 phase in NCI-H460 cell cycle, which might be depended on the ability of these compounds to affect the expression of cell cycle related proteins.

Synthesis, antiproliferative activity and mechanism of gallium(III)-thiosemicarbazone complexes as potential anti-breast cancer agents

Five thiosemicarbazone ligands were synthesized and characterized by condensation with different aldehydes or ketones by 4-phenylthiosemicarbazone. The representative dichlorido[2-(Di-2-pyridinylmethylene)-Nphenylhydrazinecarbothioamide-N,N,S]-gallium(III) (Ga4) was characterized by X-ray single crystal diffraction, which was 1:1 ligand/Ga(III) complexes. The structure-activity relationship of these ligands and Ga (III) complexes have been investigated, and the results demonstrate that the formation of Ga (III) complexes have significant antiproliferative activity over the corresponding ligands. The anticancer mechanism of gallium (III) complexes has been studied in detail, which is typical agents that effect on the mitochondrial apoptotic pathway. The ability of gallium (III) complexes to inhibit the cell cycle does not enhanced with the increasing concentrations, whereas the ability to promote apoptosis is concentration-dependent.

Improving the efficiency of Fenton reactions and their application in the degradation of benzimidazole in wastewater

Reducing the quantity of sludge produced in Fenton reactions can be partly achieved by improving their efficiency. This paper firstly studies the effect of uniform deceleration feeding (ferrous iron and hydrogen peroxide) on the efficiency of a Fenton reaction by measuring the yield of hydroxyl radicals (˙OH) and chemical oxygen demand (COD) removal rate. The dynamic behavior of ˙OH was also investigated. The results indicated that uniform deceleration feeding was the best feeding method compared with one-time feeding and uniform feeding methods when the same amount of Fenton reagents and the same reaction times were used. Besides, it was found the COD removal rate reached 79.3% when this method was applied to degrade 2-(a-hydroxyethyl)benzimidazole (HEBZ); this COD removal rate is larger than those when the other two modes were used (they reached 60.7% and 72.1%, respectively). The degradation pathway of HEBZ was determined using PL, UV-vis, FTIR, HPLC and GC-MS. Ultimately, HEBZ was decomposed into three small molecules (2-hydroxypropylamine, oxalic acid, and 2-hydroxypropamide). This research is of great significance for the application of Fenton reactions in wastewater treatment.

Gallium(III)–2-benzoylpyridine-thiosemicarbazone complexes promote apoptosis through Ca2+ signaling and ROS-mediated mitochondrial pathways

Ga(III) compounds are highly promising candidates for antitumor therapy. The level of intracellular reactive oxygen species (ROS) is significantly increased after Ga(III) complex treatment, but these complexes are redox-inactive. To investigate the effects of Ga(III) complexes on ROS levels, we synthesized three bis-ligated gallium(III)–2-benzoylpyridine-thiosemicarbazone complexes and studied their antitumor mechanisms. The structures of the Ga(III) complexes were identified by X-ray single-crystal diffraction. Cytotoxicity analysis demonstrated that the ligands and gallium complexes exerted a higher antitumor activity and a lower cytotoxicity than those of normal cells. The most active complex was C3, which exhibited a better antitumor viability than its related ligands and the anticancer agent 3-AP. Thus, the Ga(III) complexes not only transmitted the iron ions but also induced intracellular Ca2+ release. As a result, the ROS standards in redox-active iron complexes were increased. The mechanism involved the release of Cyt C from the mitochondria which lack membrane potential, and then the activation of the caspase family proteins stimulated cell apoptosis.

Gallium(III) complexes of α-N-heterocyclic piperidylthiosemicarbazones: Synthesis, structure-activity relationship, cellular uptake and activation of caspases-3/7/9

Two types of α-N-heterocyclic piperidylthiosemicarbazone ligands and related Ga(III) complexes were synthesized. The structure of Ga4 and Ga5 were characterized by X-ray single crystal diffraction. We generated the related α-N-heterocycliperidinylthiosemicarbazone analogs to examine the effect of aldehydes or ketones in the Schiff base. The antitumor activity of both type ligands increased after coordination with gallium. Interestingly, the antitumor activity of gallium complexes containing pyridyl groups (first type ligands) is higher than that of pyrazine group-containing (second type ligands) complexes. Gallium complexes significantly depleted cellular iron, resulting in upregulation of transferrin receptor-1 and downregulation of ferritin. They also effectively activate the caspase family proteins (caspase-3/7/9), promote the release of cytochromes from the mitochondria, and ultimately lead to apoptosis.

Piperidylthiosemicarbazones Cu(II) complexes with a high anticancer activity by catalyzing hydrogen peroxide to degrade DNA and promote apoptosis

Copper(II) complexes efficiently catalyze hydrogen peroxide to generate reactive oxygen species (ROS), which is the major reason for its significant anti-tumor activity. We synthesized three Cu(II) piperidylthiosemicarbazone complexes and examined their structures by X-ray single crystal diffraction. These Cu(II) complexes have significant apoptosis-promoting activity at nanomolar concentrations. The antitumor activity of these Cu(II) complexes is increased by more than 40-fold relative to that of the ligand. The binding experiment results demonstrated that the Cu(II) complexes interact with DNA with moderate binding affinity by in situ intercalation. Gel electrophoresis analysis indicated that DNA is degraded when the copper complex catalyzes hydrogen peroxide to produce reactive oxygen species (ROS). Apoptosis mechanism results showed that excessive ROS leads to mitochondrial membrane potential dissipation and promote the release of apoptotic factors from mitochondria.

A facile DNA strand displacement reaction sensing strategy of electrochemical biosensor based on N-carboxymethyl chitosan/molybdenum carbide nanocomposite for microRNA-21 detection

Herein, we report a facile enzyme-free microRNA (miRNA) target-triggered strand displacement reaction (SDR) amplification strategy with ferrocene (Fc) as a signal molecule to fabricate a two-dimensional electroactive molybdenum carbide (Mo2C)-based biosensor. In the presence of miRNA-21, SDR was initiated and many hairpin DNA1 (HDNA1) and hairpin DNA2 (HDNA2) duplexes, which could be captured by probe DNA leading the Fc-modified HDNA2 close to the electrode surface, were produced continuously. MiRNA-21 could be detected by monitoring the redox signal of Fc. The prepared N-carboxymethyl chitosan/Mo2C nanocomposite featured excellent conductivity, great dispersion, and multiple functional groups (amine groups). When the nanocomposite was introduced to a miRNA biosensor electrode interface to ensure its strong connection to the DNA probe, the developed miRNA-21 biosensor demonstrated a reliable linear range of 1.0 fM to 1.0 nM with a detection limit of 0.34 fM and showed good selectivity, reproducibility, and stability. The biosensor was employed to detect miRNA-21 in human serum samples, and it showed great potential in the early clinical diagnosis of various genetic diseases.

Evaluation of the antibacterial activity of a cationic polymer in aqueous solution with a convenient electrochemical method

AbstractQuaternized chitosan is a cationic biopolymer with good antibacterial activity, biocompatibility, and biodegradability, and it has been widely applied in many fields. We have developed a convenient method to evaluate the antibacterial activity of hydroxypropyltrimethylammonium chloride chitosan (HACC) with a nonionic surfactant poloxamer in aqueous solution by monitoring the change of the oxidation peak current in cyclic voltammetry. Increasing values of the oxidation peak current were positively correlated with the antibacterial activity of HACC–poloxamer solutions. Optical microscope images, the zeta potential, and fluorescence spectroscopy showed that the aggregation state of HACC–poloxamer was related to the ratio of the two polymers and also to the antibacterial activity and oxidation peak current. At an HACC-to-poloxamer ratio of 1:0.75, the maximum surface charge density and the smooth edge of HACC–poloxamer aggregates can accelerate diffusion in aqueous solution. It is expected that this convenient method can be applied for a quick evaluation of the antibacterial activity of cationic biopolymers in aqueous solution. Graphical AbstractThe cyclic voltammograms of MB in HACC/poloxamer solution, and the antibacterial efficiency against S. aureus after incubated with HACC (a) and 1/0.75 of HACC/poloxamer (b)