Improved 2-pyridyl reductive homocoupling reaction using biorenewable solvent Cyrene™ (dihydrolevoglucosenone).

The synthesis of 5,5'-bis(trifluoromethyl)-2,2'-bipyridine using 2-bromo-5-(trifluoromethyl) pyridine was achieved at 50 °C using palladium acetate, tetrabutylammonium iodide (TBAI), potassium carbonate, and isopropanol in Cyrene™ (dihydrolevoglucosenone), a bio-renewable "green" solvent formed by a two-step process from cellulose. Improvements were achieved with 50% of γ-valerolactone (GVL) in Cyrene™ resulting in a 95% yield and 99% product purity without the use of column chromatography or recrystallization. At 80 °C, the reaction was completed within 1 h. Full conversion with 1 mol% instead of 15 mol% of palladium acetate was observed within 10 h. We showed that the formed 2,2'-bipyridine product significantly accelerated the reaction probably due to the stabilization of the catalytic species. The addition of TBAI was essential for the rapid homocoupling, however, 20 mol% of TBAI was sufficient to reach full conversion of 2-bromo-5-(trifluoromethyl) pyridine within 6 h at 80 °C. Another improvement was observed with the substitution of isopropanol by 1,4-butanediol achieving full conversion within 6 h. 2-Bromopyridines with electron withdrawing substituents in the 6, 5, 4 ring position reacted under these conditions. 2-Bromopyridines with an electron donating substituent reacted slower. Overall, we demonstrated that the 50% GVL in Cyrene™ blend is a superior "green" and less toxic alternative to dimethylformamide for the reductive homocoupling reaction. Using a quantitative scoring for twelve principles of green chemistry (DOZN™), we found significant improvements that were mediated by higher yield (atom economy), shorter heating time and lower reaction temperature (energy efficiency), safer solvent (hazardous chemical synthesis), and safer chemistry (accident prevention).

Biosensor Design for the Detection of Circulating Tumor Cells Using the Quartz Crystal Resonator Technique.

A new mass-sensitive biosensing approach for detecting circulating tumor cells (CTCs) using a quartz crystal resonator (QCR) has been developed. A mathematical model was used to design a ring electrode-based QCR to eliminate the Gaussian spatial distribution of frequency response in the first harmonic mode, a characteristic of QCRs, without compromising the sensitivity of frequency response. An ink-dot method was used to validate the ring electrode fabricated based on our model. Furthermore, the ring electrode QCR was experimentally tested for its ability to capture circulating tumor cells, and the results were compared with a commercially available QCR with a keyhole electrode. An indirect method of surface immobilization technique was employed via modification of the SiO2 surface of the ring electrode using a silane, protein, and anti-EpCAM. The ring electrode successfully demonstrated eliminating the spatial nonuniformity of frequency response for three cancer cell lines, i.e., MCF-7, PANC-1, and PC-3, compared with the keyhole QCR, which showed nonuniform spatial response for the same cancer cell lines. These results are promising for developing QCR-based biosensors for the early detection of cancer cells, with the potential for point-of-care diagnosis for cancer screening.

Gold Nanorod Substrate for Rat Fetal Neural Stem Cell Differentiation into Oligodendrocytes.

Gold nanorods (AuNRs) have been proposed to promote stem cell differentiation in vitro and in vivo. In this study, we examined a particular type of AuNR in supporting the differentiation of rat fetal neural stem cells (NSCs) into oligodendrocytes (ODCs). AuNRs were synthesized according to the seed-mediated method resulting in nanorods with an aspect ratio of around 3 (~12 nm diameter, 36 nm length) and plasmon resonance at 520 and 780 nm, as confirmed by transmission electron microscopy (TEM) and UV-vis spectroscopy, respectively. A layer-by-layer approach was used to fabricate the AuNR substrate on the functionalized glass coverslips. NSCs were propagated for 10 days using fibroblast growth factor, platelet-derived growth-factor-supplemented culture media, and differentiated on an AuNR or poly-D-lysine (PDL)-coated surface using differentiation media containing triiodothyronine for three weeks. Results showed that NSCs survived better and differentiated faster on the AuNRs compared to the PDL surface. By week 1, almost all cells had differentiated on the AuNR substrate, whereas only ~60% differentiated on the PDL surface, with similar percentages of ODCs and astrocytes. This study indicates that functionalized AuNR substrate does promote NSC differentiation and could be a viable tool for tissue engineering to support the differentiation of stem cells.

Cellular Uptake of Gold Nanorods in Breast Cancer Cell Lines.

Nanosized materials have been proposed for a wide range of biomedical applications, given their unique characteristics. However, how these nanomaterials interact with cells and tissues, as well as how they bio-distribute in organisms, is still under investigation. Differences such as the nanoparticle size, shape, and surface chemistry affect the basic mechanisms of cellular uptake and responses, which, in turn, affects the nanoparticles' applicability for biomedical applications. Thus, it is vital to determine how a specific nanoparticle interacts with cells of interest before extensive in vivo applications are performed. Here, we delineate the uptake mechanism and localization of gold nanorods in SKBR-3 and MCF-7 breast cancer cell lines. Our results show both differences and similarities in the nanorod-cell interactions of the two cell lines. We accurately quantified the cellular uptake of gold nanorods in SKBR-3 and MCF-7 using inductively coupled plasma mass spectrometry (ICP-MS). We found that both cell types use macropinocytosis to internalize bare nanorods that aggregate and associate with the cell membrane. In addition, we were able to qualitatively track and show intracellular nanoparticle localization using transmission electron microscopy. The results of this study will be invaluable for the successful development of novel and "smart" nanodrugs based on gold nano-structural delivery vehicles, which heavily depend on their complex interactions with single cells.

Development of a polymeric biomedical device platform with controlled disassembly and in vivo testing in a swine intestinal model.

The aim of this study was to create a surgical guide platform that maintains its integrity while the surgeon performs an intestinal anastomosis or another similar procedure, which then breaks apart and is eliminated from the body in a controlled manner. The device contains mixed polymeric structures that give it a controlled rate of disassembly that could meet the requirements of a specific surgical purpose. The intraluminal anastomotic guide was manufactured as a hollow cylinder composed of layers of porous polyurethane/PCL with polyvinylpyrrolidone as the binding agent similar to a "brick-mortar" architecture. This combination of polymeric structures is a promising manufacturing method from which a variety of tunable devices can be fabricated for specific medical procedures and site-specific indications. The guide was designed to rapidly disassemble within the intestinal lumen after use, reliably degrading while maintaining sufficient mechanical rigidity and stability to support manipulation during complex surgical procedures. The nature of the device's disassembly makes it suitable for use in hollow structures that discharge their contents, resulting in their elimination from the body. A swine model of intestinal anastomosis was utilized to validate the use and function of the device.