Changyu Wu

Photoelectrocatalytic oxidation of glutathione based on porous TiO2-Pt nanowhiskers.

The performance of TiO(2) nanoparticles is extremely attractive in various areas of chemical and biochemical engineering as they can effectively work by combining the photocatalytic property with various superior properties of the related nanostructure. The relevant photoelectrochemical detection has attracted considerable interest and shown potential applications in a wide range of areas. In this study, we have prepared new nanowhiskers of platinum-doped titanium dioxide (TiO(2)-Pt), which could be further used to fabricate a novel nanointerface for the sensitive detection of biomolecules including glutathione (GSH). Our observations demonstrate that the sensitive TiO(2)-Pt nanowhiskers biointerface could be readily fabricated by casting the TiO(2)-Pt nanowhiskers suspension on a glassy carbon electrode (GCE), which could readily combine the photocatalytic and eletrocatalytic properties of TiO(2) nanocomposites to introduce a novel photoelectrocatalytic biosensor for GSH detection in real samples. Compared to other analysis strategies, the TiO(2)-Pt nanowhiskers-modified GCE showed a considerably high sensitivity for the detection of GSH due to the excellent photoelectrocatalytic ability of the porous TiO(2)-Pt nanowhiskers. Scanning electron microscopy (SEM), Raman spectroscopy, and electrochemical impedance spectroscopy have shown that Pt can readily blend with porous TiO(2) nanowhiskers and facilitate the relevant catalysis property of TiO(2), resulting in the enhanced photoelectrocatalytic effect. Thus, through the new strategy of the utilization of the excellent photoelectrocatalytic property of TiO(2)-Pt nanocomposites, it is possible to realize the rapid electrochemical detection of glutathione with high sensitivity, low cost, and good reproducibility.

Antimicrobial activity of a ferrocene-substituted carborane derivative targeting multidrug-resistant infection.

Multidrug resistance (MDR) of bacteria is still an unsolved serious problem to threaten the health of human beings. Developing new antibacterial agents, therefore, are urgently needed. Herein, we have explored the possibility to design and synthesize some novel antibacterial agents including ferrocene-substituted carborane derivative (Fc(2)SBCp(1)) and have evaluated the relevant antibacterial action against two clinical common MDR pathogens (i.e., Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa) in vitro and in vivo. The results demonstrate that in vitro antimicrobial activity of Fc(2)SBCp(1) could be gradually transformed into a bactericidal effect from a bacteriostatic effect with the increasing concentration of the active carborane derivative, which can also prevent biofilm formation at concentrations below MIC (i.e., minimal inhibitory concentration). Biocompatibility studies indicate that there exists no/or little toxic effect of Fc(2)SBCp(1) on normal cells/tissues and leads to little hemolysis. In vivo studies illustrate that the new carborane derivative Fc(2)SBCp(1) is highly effective in treating bacteremia caused by S. aureus and P. aeruginosa as well as interstitial pneumonia caused by S. aureus. This raises the possibility for the potential utilization of the new ferrocene-substituted carborane derivatives as promising antibacterial therapeutic agents against MDR bacterial infections in future clinical applications.

Multifunctional effects of Cys–CdTe QDs conjugated with gambogic acid for cancer cell tracing and inhibition

We have studied the multifunctional effects of cysteamine-coated cadmium–tellurium quantum dots (Cys–CdTe QDs) conjugated with gambogic acid (GA) for cancer cell labeling and cancer treatment. Our results indicated that the Cys–CdTe QDs (about 3 nm) could readily bind on the cell plasma membranes and then be internalized into cancer cells for real-time tracing and treatment of human leukemia cancers. The positively charged surface of the self-assembled and conjugated GA with the Cys–CdTe QDs could significantly enhance the drug accumulation into leukemia K562 cells and the drugs cytotoxicity, to inhibit the cancer cell proliferation. The GA–Cys–CdTe nanocomposites improved the drug action to overcome the multidrug resistance of K562/A02 cells and facilitated the GA induced G0/G1 phase cancer cell cycle arrest to promote cell apoptosis. Moreover, the sensitive pH-triggered release behavior of the relevant nanocomposites, loaded with GA, greatly reduced the side effects of the anticancer agents to the normal cells/tissues in the blood circulation and facilitated an efficient drug release and accumulation in the target tumor cells. Thus, the combination of an active compound from Traditional Chinese Medicine (TCM), GA, with Cys–CdTe QDs can afford a new strategy for the potential multimode cancer therapy.

Green and facile synthesis of highly biocompatible carbon nanospheres and their pH-responsive delivery of doxorubicin to cancer cells

Developing an efficient nanoparticulate drug-delivery system with a sub-100 nm diameter plays a crucial role in delivering antitumor drugs into cancer cells and improving their therapeutic efficacy. Carbon spheres, due to their large surface areas, unique surface properties and ease of functionalization, can generally deliver a large quantity of therapeutic agents to the target disease sites. In this study, spherical carbon nanoparticles with uniform size (71 nm) and regular shape were synthesized by hydrothermal reaction of bacterial cellulose nanofibers (30–50 nm), which had been achieved by a microorganism synthesis. Then using a simple acidification treatment, we could obtain carbon nanospheres with high drug loading capacity (the drug encapsulation efficiency was found to be about 93.4% and the drug loading efficiency (DL) reached about 52.3%). Meanwhile, the carbon nanospheres also exhibited good pH sensitivity in drug delivery. The results of in vitro experiments demonstrate that the carbon nanospheres prepared played an important part in the increase of the intracellular drug concentration and delayed-efficacy of the drug effect, which make them a promising platform for the delivery of other therapeutic agents beyond DOX.

Enhanced in vitro anticancer activity of quercetin mediated by functionalized CdTe QDs

We report in this study the effects of red-emitting CdTe QDs capped with cysteamine (Cys-CdTe) on the in vitro anticancer activity of the well-known flavenoid quercetin (Qu). Various techniques, including the methylthiazolyldiphenyl-tetrazolium bromide assay, the real-time cell electronic sensing system, the optical and fluorescence imaging, and electrochemical methods have been utilized to study the potential interactions of Cys-CdTe QDs with Qu. The observations demonstrate that the safe-dosage Cys-CdTe QDs can greatly improve the drug uptake and enhance the inhibition efficiency of Qu towards the proliferation of cancer cells such as HepG2 cells. This study implies that Cys-CdTe QDs may be used for cancer therapy and that they exert a synergic anticancer effect when bound to drug molecules.

Real-Time Evaluation of Live Cancer Cells by an in Situ Surface Plasmon Resonance and Electrochemical Study

This work presents a new strategy of the combination of surface plasmon resonance (SPR) and electrochemical study for real-time evaluation of live cancer cells treated with daunorubicin (DNR) at the interface of the SPR chip and living cancer cells. The observations demonstrate that the SPR signal changes could be closely related to the morphology and mass changes of adsorbed cancer cells and the variation of the refractive index of the medium solution. The results of light microscopy images and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide studies also illustrate the release or desorption of HepG2 cancer cells, which were due to their apoptosis after treatment with DNR. It is evident that the extracellular concentration of DNR residue can be readily determined through electrochemical measurements. The decreases in the magnitudes of SPR signals were linearly related to cell survival rates, and the combination of SPR with electrochemical study could be utilized to evaluate the potential therapeutic efficiency of bioactive agents to cells. Thus, this label-free, real-time SPR-electrochemical detection technique has great promise in bioanalysis or monitoring of relevant treatment processes in clinical applications.

New strategy for reversing biofilm-associated antibiotic resistance through ferrocene-substituted carborane ruthenium(II)-arene complex

Bacterial biofilms are inherently resistant to antimicrobial agents and are difficult to eradicate with conventional antimicrobial agents, resulting in many persistent and chronic bacterial infections. In this contribution, a new strategy for reversing the biofilm-associated antibiotic resistance has been explored by induction of a carborane ruthenium(II)-arene complex (FcRuSB). Our results demonstrate that the FcRuSB could be utilized as an inducer to efficiently reverse the biofilm-associated antibiotic resistance of multidrug-resistant (MDR) clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa. The induced effect of FcRuSB is correlated with a considerable decrease in the expression of extracellular matrix proteins (EMP) of the two strains. The considerable decrease of the EMP of induced cells, resulting in the reduction of adherence and biofilm formation ability of the two types of MDR pathogens, and then can cause significantly enhanced sensitivity of them to antibiotics.

Discovery of ferrocene-carborane derivatives as novel chemical antimicrobial agents against multidrug-resistant bacteria

Antimicrobial resistance has now become a very serious global public health problem. New drug discovery and development are urgently needed to combat the growing threat of multidrug-resistant (MDR) bacteria. The aim of this study was to explore the potential application of three ferrocene-carborane derivatives as new promising agents to confront the problem of increasing antibiotic resistance. The results of agar diffusion bioassay, minimal inhibitory concentrations (MIC) testing and time-kill assay illustrate their broad-spectrum antimicrobial activities to both American Type Culture Collection (ATCC) control strains and MDR clinical isolates. It is evident that the relevant antimicrobial properties are all in a dose-dependent manner and gradually transform into a bactericidal effect from a bacteriostatic effect with the increasing of the drug concentration. Furthermore, these ferrocene-carborane derivatives have no/little toxic effect on normal cells like HELF cells and lead to little hemolysis at their MICs. This raises the possibility to develop novel antimicrobial drugs using these new ferrocene carborane derivants.

Size-controlled porous superparamagnetic Zn1/3Fe8/3O4 nanospheres: synthesis, properties and application for drug delivery

Magnetic nanospheres have recently attracted much attention in the biomedical areas due to their good biocompatibility and unique magnetic features. Herein we report the synthesis and characterization of different sized porous superparamagnetic iron oxide nanospheres (SPIONs) (Zn1/3Fe8/3O4) which are based on a new rational method of elevated-temperature hydrolysis of chelate iron alkoxide complexes in solutions of the corresponding alcohol, diethyleneglycol (DEG) and diethanolamine (DEA). The size of the SPIONs is controlled by changing the ratio of the reaction media. It is noted that the highly water dispersible porous SPIONs with narrow size distribution can be tuned from 6.5 to 200 nm, each of which is composed of many single magnetite crystallites of approximately 5.5 nm in size. The SPIONs show superparamagnetic properties at room temperature. The superparamagnetic behavior, high magnetization, and high water dispersibility make these nanospheres ideal candidates for various important applications for drug delivery.

Synergy and translation of allogenic bone marrow stem cells after photodynamic treatment of rheumatoid arthritis with tetra sulfonatophenyl porphyrin and TiO2 nanowhiskers

Rheumatoid arthritis (RA) etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell (BMSC) translation and photodynamic treatment of RA with tetra sulfonatophenyl porphyrin (TSPP) and TiO2 nanocomposites as a new strategy for RA theranostics. The translation of BMSCs with miRNAs into infected joints in long bones post-photodynamic therapy is helpful for treating and understanding RA pathophysiology. We observed that allogenic BMSC translation combined with TSPP-TiO2 nanocomposites can significantly (p < 0.01) lower the concentrations of serum biomarkers (tumor necrosis factor-α and interleukin-17) in a collagen induced arthritis (CIA) murine model, both in vitro and in vivo, as well as improve other parameters such as arthritis score, BMSC count, complete blood count, and numbers of platelets, red blood cells, and white blood cells. Moreover, a fluorescent TSPP in the feet or long bones and X-ray bioimaging of RA joints revealed the clinical efficacy of BMSCs combined with TSPP-TiO2 nanocomposites. Microarray data analysis illustrated that rno-mir-375-3p and rno-mir-196b-3p were up-regulated by approximately 100-fold in the BMSCs of ameliorated RA post-photodynamic therapy with TSPP-TiO2 nanocomposites. Our study not only suggests a new approach for RA theranostics, but also helps in understanding RA pathophysiology.