ß-elemene Isopropanolamine Derivative LXX-8250 Induces Apoptosis Through Impairing Autophagic Flux via PFKFB4 Repression in Melanoma Cells.

Melanoma is a highly aggressive skin cancer and accounts for most of the skin cancer-related deaths. The efficacy of current therapies for melanoma remains to be improved. The isopropanolamine derivative of ß-elemene LXX-8250 was reported to present better water solubility and stronger toxicity to tumor cells than ß-elemene. Herein, LXX-8250 treatment showed 4-5-fold more toxicity to melanoma cells than the well-known anti-melanoma drug, Dacarbazine. LXX-8250 treatment induced apoptosis remarkably, which was caused by the impairment of autophagic flux. To clarify the molecular mechanism, microarray analyses were conducted, and PFKFB4 expression was found to be suppressed by LXX-8250 treatment. The cells overexpressed with PFKFB4 exhibited resistance to apoptosis induction and autophagic flux inhibition by LXX-8250 treatment. Moreover, LXX-8250 treatment suppressed glycolysis, to which the cells overexpressed with PFKFB4 were tolerant. LXX-8250 treatment inhibited the growth of melanoma xenografts and suppressed PFKFB4 expression and glycolysis in vivo. Taken together, LXX-8250 treatment induced apoptosis through inhibiting autophagic flux and glycolysis in melanoma cells, which was mediated by suppression of PFKFB4 expression. The study provides a novel strategy to melanoma treatment.

Bcl-2-functionalized ultrasmall superparamagnetic iron oxide nanoparticles coated with amphiphilic polymer enhance the labeling efficiency of islets for detection by magnetic resonance imaging.

Based on their versatile, biocompatible properties, superparamagnetic iron oxide (SPIO) or ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are utilized for detecting and tracing cells or tumors in vivo. Here, we developed an innoxious and concise synthesis approach for a novel B-cell lymphoma (Bcl)-2 monoclonal antibody-functionalized USPIO nanoparticle coated with an amphiphilic polymer (carboxylated polyethylene glycol monooleyl ether [OE-PEG-COOH]). These nanoparticles can be effectively internalized by beta cells and label primary islet cells, at relatively low iron concentration. The biocompatibility and cytotoxicity of these products were investigated by comparison with the commercial USPIO product, FeraSpin(™) S. We also assessed the safe dosage range of the product. Although some cases showed a hypointensity change at the site of transplant, a strong magnetic resonance imaging (MRI) was detectable by a clinical MRI scanner, at field strength of 3.0 Tesla, in vivo, and the iron deposition/attached in islets was confirmed by Prussian blue and immunohistochemistry staining. It is noteworthy that based on our synthesis approach, in future, we could exchange the Bcl-2 with other probes that would be more specific for the targeted cells and that would have better labeling specificity in vivo. The combined results point to the promising potential of the novel Bcl-2-functionalized PEG-USPIO as a molecular imaging agent for in vivo monitoring of islet cells or other cells.

The role of exendin-4-conjugated superparamagnetic iron oxide nanoparticles in beta-cell-targeted MRI.

Noninvasive targeted visualization of pancreatic beta cells or islets is becoming the focus of molecular imaging application in diabetes and islet transplantation studies, but it is currently unsuccessful due to the lack of specific beta cell biomarkers. Glucagon-like peptide 1 receptor (GLP-1R) is highly expressed in beta cells and considered as a promising target. We here developed a targeted superparamagnetic iron oxide (SPIO) nanoparticle using GLP-1 analog-exendin-4 which is conjugated to polyethylene glycol coated SPIO (PEG-SPIO). The results demonstrated that exendin-4 functionalized SPIO was able to specifically bind to and internalized by GLP-1R-expressing INS-1 cells, with the higher labeling efficiency than non-targeted nanoparticles. Notably, SPIO-exendin4 could differentially label islets in pancreatic slices or beta cell grafts in vitro. Systemic delivery of SPIO-exendin4 into nude mice bearing s.c. insulinomas (derived from INS-1 cells) leads to the accumulation of the nanoparticles in tumors, generating a strong magnetic resonance imaging contrast detectable by a clinical MRI scanner at field strength of 3.0 T, and the iron deposition in tumors was further confirmed by Prussian blue staining. Furthermore, preliminary biodistribution study indicated that SPIO-exendin4 had a tendency to accumulate in pancreas. Toxicity assessments demonstrated good biocompatibility in vivo. These results suggest that SPIO-exendin4 has potential as molecularly targeted imaging agents for in vivo imaging of insulinoma, and possibly for future beta cell imaging.

Layer-by-layer synthesis of γ-Fe2O3@SnO2@C porous core-shell nanorods with high reversible capacity in lithium-ion batteries.

We demonstrated the layer-by-layer synthesis of γ-Fe2O3@SnO2@C porous core-shell nanorods. FeOOH nanorods were first synthesized via a hydrothermal process, and acted as a template for subsequent layer-by-layer deposition. It was indicated that the electrostatic attraction between the charged species may play the key role in the formation of the core-shell nanostructures. When used as an anode material in lithium-ion batteries, γ-Fe2O3@SnO2@C porous core-shell nanorods showed high initial Coulombic efficiency, high reversible capacity, and good cycling and rate performances. The correlation between the structure, composition and electrochemical performance was also discussed.

Detection of viability of transplanted beta cells labeled with a novel contrast agent - polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles by magnetic resonance imaging.

Islets can be visualized on MRI by labeling with superparamagnetic contrast agent during the transplantation procedure. However, whether the signal intensity reflects the cell number and cellular viability has not been determined. We used a self-synthesized novel superparamagnetic contrast agent -polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) - to label ß-TC-6 cells (a mouse insulinoma cell line) or primary islets with commercial Feridex as a control. The labeling efficiency of two agents was compared by Prussian blue staining, intracellular iron content determination and MR scanning. Cells were exposed to hypoxia, high-glucose or exogenous H2O2 stimulation before/after PVP-SPIO labeling. Normal and injured cells were also transplanted into renal subcapsule. A clinically used 3.0 T MR scan was performed in vitro and 24 h post-transplantation to investigate the correlation between cellular viability and signal. Our PVP-SPIO displayed superior biocompatibility and magnetic properties. All of the cells could be labeled at 100 µg/ml iron concentration after 24 h incubation. At 100 µg/ml iron concentration, 1 × 105 ß cells labeled with PVP-SPIO could already be visualized in vitro by MRI, less than the detection threshold of Feridex. There existed a linear correlation between the number of labeled cells and R2 value on the T2 -weighted images. The signal intensity and the intracellular iron content declined along with the decreased viability of labeled cells. There was also a significant difference in signal intensity between injured and normal labeled cells after transplantation. From these results, we concluded that PVP-SPIO possessed superior cell labeling efficiency, and ß cells could be labeled without compromising viability and function. The signal intensity on MRI might be a useful predictor to evaluate the number and the viability of PVP-SPIO-labeled cells.

Multiwalled carbon nanotubes anchored with SnS2 nanosheets as high-performance anode materials of lithium-ion batteries.

A nanocomposite of multiwalled carbon nanotubes (MWCNTs) anchored with SnS(2) nanosheets (NS) (SnS(2) NS@MWCNTs coaxial nanocables) has been synthesized through a simple solution-based method at room temperature. The synthetic mechanism of these intriguing nanocomposites is proposed as electrostatic attraction between tin ions and MWCNTs, followed by the nucleation and two-dimensional growth of SnS(2). The as-synthesized SnS(2) NS@MWCNTs coaxial nanocables have been applied as anode materials for lithium-ion batteries, which show better lithium storage performance compared to pure SnS(2) nanosheets and MWCNTs. The combination of MWCNTs that can hinder the agglomeration and enhance electronic conductivity of the active materials might be responsible for the enhanced cyclic performance.

Self-templating synthesis of SnO2-carbon hybrid hollow spheres for superior reversible lithium ion storage.

This paper reports a novel self-templating methodology for the formation of SnO(2)-carbon hybrid hollow spheres by using Sn spheres as sacrificing templates. The time-sequenced structural evolution of the templates indicates that the nanoscale Kirkendall effect plays a critical role in the transformation from Sn spheres to the hybrid hollow spheres. Moreover, the as-synthesized SnO(2)-carbon hybrid hollow spheres have been applied as anode materials for lithium-ion batteries, which exhibit a much higher initial Coulombic efficiency and better cycling performance than pure SnO(2) hollow spheres.

Assembling CoSn3 nanoparticles on multiwalled carbon nanotubes with enhanced lithium storage properties.

CoSn(3) nanoparticles have been successfully assembled on noncovalently poly(diallyldimethylammonium chloride)-functionalized multiwalled carbon nanotubes (MWCNTs) via a chemical reduction method in a polyol system. The influences of the surface functionality and the reaction temperature on the synthesis of uniform CoSn(3)-MWCNTs nanohybrids have been investigated. The as-synthesized CoSn(3)-MWCNTs nanohybrids have been applied as anodes for lithium-ion batteries, and show better lithium storage performance compared to the bare CoSn(3) nanoparticles and MWCNTs. The combining of MWCNTs that can hinder the agglomeration and enhance the electronic conductivity of the active materials is responsible for the enhanced cyclic performance.

Porous ZnCo2O4 nanowires synthesis via sacrificial templates: high-performance anode materials of Li-ion batteries.

A simple microemulsion-based method has been developed to synthesize ZnCo(2)(C(2)O(4))(3) nanowires that can be transformed to porous ZnCo(2)O(4) nanowires under annealing conditions. The morphology of porous ZnCo(2)O(4) nanowires can be tuned by the initial ZnCo(2)(C(2)O(4))(3) nanowires and the annealing temperatures. The as-synthesized porous ZnCo(2)O(4) nanowires have been applied as anode materials of Li-ion batteries, which show superior capacity and cycling performance. The porous one-dimensional (1D) nanostructures and large surface area are responsible for the superior performance. Moreover, it is indicated that porous ZnCo(2)O(4) nanowires synthesized at low annealing temperature (500 °C) show larger capacity and better cycling performance than that prepared at high annealing temperature (700 °C), because of their higher porosity and larger surface area.

One-Pot Synthesis of Biocompatible CdSe/CdS Quantum Dots and Their Applications as Fluorescent Biological Labels.

We developed a novel one-pot polyol approach for the synthesis of biocompatible CdSe quantum dots (QDs) using poly(acrylic acid) (PAA) as a capping ligand at 240°C. The morphological and structural characterization confirmed the formation of biocompatible and monodisperse CdSe QDs with several nanometers in size. The encapsulation of CdS thin layers on the surface of CdSe QDs (CdSe/CdS core-shell QDs) was used for passivating the defect emission (650 nm) and enhancing the fluorescent quantum yields up to 30% of band-to-band emission (530-600 nm). Moreover, the PL emission peak of CdSe/CdS core-shell QDs could be tuned from 530 to 600 nm by the size of CdSe core. The as-prepared CdSe/CdS core-shell QDs with small size, well water solubility, good monodispersity, and bright PL emission showed high performance as fluorescent cell labels in vitro. The viability of QDs-labeled 293T cells was evaluated using a 3-(4,5-dimethylthiazol)-2-diphenyltertrazolium bromide (MTT) assay. The results showed the satisfactory (>80%) biocompatibility of as-synthesized PAA-capped QDs at the Cd concentration of 15 µg/ml.

Large-scale synthesis of water-soluble nanowires as versatile templates for nanotubes.

This study presents a large-scale synthesis of water-soluble sodium fluosilicate (Na(2)SiF(6)) nanowires, which serve as a versatile template for producing nanotubes.

Large-scale synthesis of ultrathin hexagonal tin disulfide nanosheets with highly reversible lithium storage.

Ultrathin hexagonal SnS(2) nanosheets are synthesized via a simple hydrothermal reaction. The nanosheets have been applied as an anode for lithium-ion battery, which shows highly reversible capacity and good cycling stability with excellent capacity retention of 96% after 50 cycles.

Selective Synthesis of Fe2O3 and Fe3O4 Nanowires Via a Single Precursor: A General Method for Metal Oxide Nanowires.

Hematite (α-Fe2O3) and magnetite (Fe3O4) nanowires with the diameter of about 100 nm and the length of tens of micrometers have been selectively synthesized by a microemulsion-based method in combination of the calcinations under different atmosphere. The effects of the precursors, annealing temperature, and atmosphere on the morphology and the structure of the products have been investigated. Moreover, Co3O4 nanowires have been fabricated to confirm the versatility of the method for metal oxide nanowires.

Labeling transplanted mice islet with polyvinylpyrrolidone coated superparamagnetic iron oxide nanoparticles for in vivo detection by magnetic resonance imaging.

Superparamagnetic iron oxide nanoparticles (SPIO) are emerging as a novel probe for noninvasive cell tracking with magnetic resonance imaging (MRI) and have potential wide usage in medical research. In this study, we have developed a method using high-temperature hydrolysis of chelate metal alkoxide complexes to synthesize polyvinylpyrrolidone coated iron oxide nanoparticles (PVP-SPIO), as a biocompatible magnetic agent that can efficiently label mice islet beta-cells. The size, crystal structure and magnetic properties of the as-synthesized nanoparticles have been characterized. The newly synthesized PVP-SPIO with high stability, crystallinity and saturation magnetization can be efficiently internalized into beta-cells, without affecting viability and function. The imaging of 100 PVP-SPIO-labeled mice islets in the syngeneic renal subcapsular model of transplantation under a clinical 3.0 T MR imager showed high spatial resolution in vivo. These results indicated the great potential application of the PVP-SPIO as an MRI contrast agent for monitoring transplanted islet grafts in the clinical management of diabetes in the near future.

Cobalt ferrite nanorings: Ostwald ripening dictated synthesis and magnetic properties.

CoFe(2)O(4) nanorings were synthesized by a simple solvothermal process, in which Ostwald ripening was definitely responsible for the formation of hollow structures, and their ferromagnetic behavior at room temperature was observed.

From cobalt nitrate carbonate hydroxide hydrate nanowires to porous Co(3)O(4) nanorods for high performance lithium-ion battery electrodes.

We have developed a simple approach for the large-scale synthesis of cobalt nitrate carbonate hydroxide hydrate (Co(CO(3))(0.35)(NO(3))(0.2)(OH)(1.1)·1.74H(2)O) nanowires via the hydrothermal process using sodium hydroxide and formaldehyde as mineralizers at 120 °C. The porous Co(3)O(4) nanorods 10-30 nm in diameter and hundreds of nanometres in length have been fabricated from the above-mentioned multicomponent nanowires by calcination at 400 °C. The morphology and structure of cobalt nitrate carbonate hydroxide hydrate nanowires and Co(3)O(4) nanorods have been characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and x-ray powder diffraction (XRD). Moreover, the porous Co(3)O(4) nanorods have been applied in the negative electrode materials for lithium ion batteries, which exhibit high electrochemical performance.