Enhanced anti-angiogenic activity of novel melatonin-like agents.

Hypoxia-inducible factor-1 (HIF-1) plays an important role in cellular responses to hypoxia, including the transcriptional activation of several genes involved in tumor angiogenesis. Melatonin, also known as N-acetyl-5-methopxytryptamine, is produced naturally by the pineal gland and has anti-angiogenic effects in cancer through its ability to modulate HIF-1α activity. However, the use of melatonin as a therapeutic is limited by its low oral bioavailability and short half-life. Here, we synthesized melatonin-like molecules with enhanced HIF-1α targeting activity and less toxicity and investigated their effects on tumor growth and angiogenesis, as well as the underlying molecular mechanisms. Among melatonin derivatives, N-butyryl-5-methoxytryptamine (NB-5-MT) showed the most potent HIF-1α targeting activity. This molecule was able to (a) reduce the expression of HIF-1α at the protein level, (b) reduce the transcription of HIF-1α target genes, (c) reduce reactive oxygen species (ROS) generation, (d) decrease angiogenesis in vitro and in vivo, and (e) suppress tumor size and metastasis. In addition, NB-5-MT showed improved anti-angiogenic activity compared with melatonin due to its enhanced cellular uptake. NB-5-MT is thus a promising lead for the future development of anticancer compounds with HIF-1α targeting activity. Given that HIF-1α is overexpressed in the majority of human cancers, the melatonin derivative NB-5-MT could represent a novel potent therapeutic agent for cancer.

Synthesis of arbutin-gold nanoparticle complexes and their enhanced performance for whitening.

Arbutin, a natural polyphenol, possesses numerous biological activities including whitening, anti-oxidant, anti-cancer, anti-inflammatory activities, as well as strong reducing power, making it an ideal bioactive ingredient for preparing gold nanoparticles (GNPs). Previously, we developed a novel green, mild synthetic method for GNPs using glycosides such as arbutin as reducing agents and stabilizers. Herein, we optimized the synthetic method for glycoside-GNPs using arbutin, methyl ß-D-glucoside, and phenyl ß-D-glucoside and validated their whitening efficacy in vitro and in vivo. The resulting glycoside-GNPs were predominantly mono-dispersed and spherical (10.30-17.13 nm diameter). Compared with arbutin itself, arbutin-GNP complexes (GNP-A1 and GNP-P2) displayed enhanced whitening capabilities. Furthermore, GNP-P2 exhibited enhanced anti-inflammatory activity and lacked the toxicity associated with arbutin. Bioactive glycoside-GNP complexes may open new directions for cosmeceuticals, and GNP-P2 may serve as a useful whitening ingredient in future cosmeceutical applications.

Stacking-Controlled Assembly of Cabbage-Like Graphene Microsphere for Charge Storage Applications.

Nanostructured graphene electrodes generally have a low density, which can limit the volumetric performance for energy storage devices. The liquid-phase mild reduction process of graphene oxide sheets is combined with the continuous aerosol densification process to produce high-density graphene agglomerates in the form of microspheres. The produced graphene assembly shows the cabbage-like morphology with a high density of 0.75 g cm-3 . In spite of such high density, the cabbage-like graphene microspheres have narrow-ranged mesopores and a high surface area. The cabbage-like graphene microsphere exhibits both high gravimetric and volumetric energy densities due to the optimized microstructure, which shows a high gravimetric capacitance of 177 F g-1 and volumetric capacitance of 117 F cm-3 in supercapacitors. As a cathode for lithium-ion capacitors, the cabbage-like graphene delivers a reversible capacity of ≈176 mAh g-1 . The stacking-control approach provides a new pathway to control the microstructure of the graphene assembly and corresponding charge storage characteristics for energy storage applications.

Enhanced Cellular Uptake and Pharmacokinetic Characteristics of Doxorubicin-Valine Amide Prodrug.

In this study, we synthesized the valine (Val)-conjugated amide prodrug of doxorubicin (DOX) by the formation of amide bonds between DOX and Val. The synthesis of the DOX-Val prodrug was identified by a proton nuclear magnetic resonance (¹H-NMR) assay. In the MCF-7 cells (human breast adenocarcinoma cell; amino acid transporter-positive cell), the cellular accumulation efficiency of DOX-Val was higher than that of DOX according to the flow cytometry analysis data. Using confocal laser scanning microscopy (CLSM) imaging, it was confirmed that DOX-Val as well as DOX was mainly distributed in the nucleus of cancer cells. DOX-Val was intravenously administered to rats at a dose of 4 mg/kg, and the plasma concentrations of DOX-Val (prodrug) and DOX (formed metabolite) were quantitatively determined. Based on the systemic exposure (represented as area under the curve (AUC) values) of DOX-Val (prodrug) and DOX (formed metabolite), approximately half of DOX-Val seemed to be metabolized into DOX. However, it is expected that the remaining DOX-Val may exert improved cellular uptake efficiency in cancer cells after its delivery to the cancer region.

One-Step Synthesis of Pt/Graphene Composites from Pt Acid Dissolved Ethanol via Microwave Plasma Spray Pyrolysis.

Pt nanoparticles-laden graphene (Pt/GR) composites were synthesized in the gas phase from a mixture of ethanol and Pt precursor by microwave plasma spray pyrolysis. The morphology of Pt/GR composites has the shape of wrinkled sheets of paper, while Pt nanoparticles (Pt NPs) that are less than 2.6 nm in the mean diameter are uniformly well deposited on the surface of GR sheets stacked in only three layers. The Pt/GR composite prepared with 20 wt% of Pt had the highest specific surface area and electrochemical surface area of up to 402 m(2) g(-1) and 77 m(2) g(-1) (Pt), respectively. In addition, the composite showed superior electrocatalytic activity compared with commercial Pt-carbon black. The excellent electrocatalytic activity was attributed to the high specific surface area and electrochemical surface area of the Pt/GR composite directly produced by microwave plasma spray pyrolysis. Thus, it is clearly expected that the Pt/GR composite is a promising material for DMFC catalysts.

Synthesis of gold nanoparticles with glycosides: synthetic trends based on the structures of glycones and aglycones.

A new, room temperature synthetic method for gold nanoparticles from auric acid with glycosides as reducing agents in aqueous NaOH is presented. As a mechanistic study of the oxidation sites on the glycosides, eight sugar-containing reductants (glycoside, glucose, glucuronic acid) have been tested in the synthesis of gold nanoparticles to determine their trends based on the structures of glycones and aglycones. As a result of the comparison among the eight sugar-containing reductants, it was determined that C-6 of glycosides is oxidized to a carboxylic acid during the reduction of auric acid. To detect the oxidized compounds of the glycosides, the reaction mixtures were monitored by (13)C NMR. Among the eight sugar-containing reductants, phenyl ß-D-glucoside generated the highest synthetic yield of mono-dispersed, round gold nanoparticles (13.15±1.30 nm, 99.7% yield).