Polyethylene glycol-decorated doxorubicin/carboxymethyl chitosan/gold nanocomplex for reducing drug efflux in cancer cells and extending circulation in blood stream.

Polyethylene glycol (PEG)-decorated doxorubicin (Dox)/carboxymethyl chitosan (CMC)/gold nanoparticles (AuNPs) have been developed for cancer therapy. CMC was used as a reducing and stabilizing agent for the fabrication of AuNPs and Dox was loaded onto AuNPs as a chemotherapeutic agent. Dox-loaded CMC-stabilized AuNPs (Dox/CMC-AuNPs) with a mean diameter of 104.0 nm, zeta potential of -48.32 mV, and drug loading efficiency of 60.14% were prepared. PEG was attached to CMC-AuNPs for enhancing systemic drug exposure and prolonging the circulation in blood stream. Compared with Dox/CMC-AuNPs, Dox-loaded PEGylated CMC-AuNPs (Dox/CMC-AuNPs-PEG) showed a reduced hydrodynamic size (71.2 nm), less negative zeta potential (-12.83 mV), and an enhanced Dox loading efficiency (73.14%). Dox/CMC-AuNPs and Dox/CMC-AuNPs-PEG exhibited sustained and pH-dependent drug release profiles and exhibited antiproliferation effects against the A549 cells. In a bi-directional transport study of Caco-2 cell monolayers, AuNPs reduced the efflux ratio, which indicated that the P-glycoprotein-mediated multidrug resistance (MDR) was overcome. Dox/CMC-AuNPs-PEG resulted in reduced drug clearance (CL) and improved half-life (t1/2), compared with Dox/CMC-AuNPs, in rats after intravenous administration. These results suggest that Dox/CMC-AuNPs-PEG could be a promising nanotherapeutic approach to overcome MDR in cancer and prolong their circulation in the blood stream.

Data mining of micrornas in breast carcinogenesis which may be a potential target for cancer prevention.

The microRNAs (miRNAs) negatively regulate the stability and translation of target messenger RNAs by selectively binding. It has been implicated in diverse processes such as cellular differentiation, cell-cycle control, apoptosis, and carcinogenesis. Examination of tumor-specific miRNA expression profiles has revealed wide spread dysregulation of these molecules in diverse cancers. The available genomic bulk evidences were extracted from The Cancer Genome Atlas by using IluminaGA_miRNASeq platform in human breast cancer samples. After mining collected data, group of each miRNA ID was analyzed through five D/Bs (mirWalk, miranda, mirDB, RNA22, and TargetScan) on predicted and validated miRNA targets. Oncogenes known to have a high correlation with breast cancer (C-myc, HER2, cyclin D-1, N-RAS, FGF-4, FGF-3, BRCA1, and BRCA2) are subject in this study to select their relevant miRNAs. Function of miRNA regulation will be essential to achieve a complete understanding of carcinogenesis and these miRNAs would be potential target for breast cancer prevention.

Effect of pre-existing oxide film on the electrochemical fabrication of nanoporous alumina film.

Different thickness of barrier-type oxide film was intentionally grown on the Al metal surface and the effect of barrier film on the formation of nanoporous aluminum oxide film during anodization was investigated to control the nanopore structure. Analysis of potential transients during anodization indicated that anodic oxide film is initially overlaid on the barrier film but the anodic film is more facile to dissolve than barrier film. As the thickness of barrier film increases, both nanopore diameter and density decrease but the pore length is irrespective of barrier-film thickness.

Electrochemical fabrication of SrTiO3 nanowires with nanoporous alumina template.

Strontium titanate nanowires were electrochemically synthesized with nanoporous alumina template. Both chemical and electrical variables such as electrolyte pH, temperature, and current waveform were modulated to investigate the synthesis process of SrTiO3 nanowires. Superimposed cathodic pulse and diffusion time accelerated the growth of SrTiO3 nanowires, which suggested that the concentration of H+ and Sr2+ ion inside alumina template had a strong influence on the formation of SrTiO3 nanowires. Morphology and crystallinity of SrTiO3 nanowires were investigated with scanning electron microscope, X-ray diffractometer and energy dispersive X-ray spectroscopy.

In vitro development of resistance to a novel fluoroquinolone, DW286, in methicillin-resistant Staphylococcus aureus clinical isolates.

In vitro development of resistance to a novel fluoroquinolone, DW286, as well as to ciprofloxacin, gemifloxacin, sparfloxacin and trovafloxacin, was investigated in eight methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. The strains were subcultured in subinhibitory concentrations of each agent during a 50 day period. Subculturing in most agents led to the selection of 37 mutants with increased MICs. The DW286 MICs were increased from 0.004-0.031 to 0.125-0.5 mg/L in five strains after 13-47 passages, and were not increased in three strains. The ciprofloxacin, gemifloxacin, sparfloxacin and trovafloxacin-selected mutants showed relatively weak cross-resistance to DW286. DNA sequencing analyses of all of the selected mutants revealed a few point mutations responsible for the high level of resistance, but actually these variations did not confer high resistance to fluoroquinolones. In the presence of reserpine, an inhibitor of the Gram-positive efflux pump, of 36 mutants 22 had two- to 16-fold lower ciprofloxacin MICs, and 20 had two- to 16-fold lower gemifloxacin MICs. However, sparfloxacin, trovafloxacin and DW286 were not good substrates for efflux pumps.

In vitro and in vivo antibacterial activities of DW286, a new fluoronaphthyridone antibiotic.

The in vitro and in vivo activities of DW286, a novel fluoronaphthyridone with potent antibacterial activity, were compared with those of ciprofloxacin, gemifloxacin, sparfloxacin, and trovafloxacin. Against gram-positive bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis, the in vitro activity of DW286 was stronger than that of any other reference antibiotic. Against gram-negative bacteria, the activity of DW286 was similar to those of trovafloxacin and gemifloxacin but was weaker than that of ciprofloxacin. In a mouse systemic infection caused by three S. aureus strains, including methicillin-resistant S. aureus and quinolone-resistant S. aureus (QRSA), DW286 demonstrated the most potent activity, as found in vitro. Specially, DW286 is >or=8-fold more active against QRSA than the other fluoroquinolones. And the 50% protective doses for DW286 were correspondent with the in vitro activities.