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We present a study on the surface-enhanced Raman scattering (SERS) properties of Ag nanoparticle island substrates (NIS) and their applications for target oligonucleotide (OND) detection. It has been found that the surface nanostructure of NIS samples can be controlled with a good degree of reproducibility, and a high SERS enhancement can be achieved when the peak extinction wavelength of NIS is tuned to a spectral window (~60 nm) between the excitation wavelength and the scattered Raman wavelength. The highest SERS enhancement was obtained from the NIS substrates with a nominal thickness of 50 [Angstrom]. Detection of target OND was performed with a sandwich format in which the target OND was hybridized both to a capture OND immobilized on the NIS substrate, and a detection OND conjugated with a Raman-active dye for SERS signal generation. We compare the detection performance of two strategies based on the use of the detection OND with or without the gold nanoparticle (Au-NP). Our results confirm that, when the detection OND is coupled to the Au-NP, a better sensitivity for the target OND detection, in terms of a wider dynamic range and a lower detection limit (0.4 fM versus 1 nM without Au-NP), would be achieved. OCIS codes: 170.5660, 300.6450, 240.6695, 240.6680.

Abstract Background Multidrug resistance (MDR) is frequently observed after prolonged treatment in human hepatoma with conventional anti-tumor drugs, and photodynamic therapy (PDT) is a recently suggested alternative to overcome MDR. The therapeutic potential of PDT was evaluated in a multidrug resistance (MDR) human hepatoma cell line R-HepG2 with photosensitizer pheophorbide a (Pa). Results Our results demonstrated that intracellular accumulation of Pa was not reduced by the overexpression of P-glycoprotein. Pa-based PDT (Pa-PDT) significantly inhibited the growth of R-HepG2 cells with an IC50 value of 0.6 μM. Mechanistic study demonstrated that genomic DNA fragmentation and phosphatidylserine externalization occurred where increase of intracellular singlet oxygen level triggers the phosphorylation of c-Jun N-terminal Kinase (JNK) and leads to activation of intrinsic apoptotic caspases cascade during the Pa-PDT treatment. The cytotoxicity of Pa-PDT, accumulation of sub-G1 population, and depolarization of mitochondrial membrane could be inhibited by JNK inhibitor in the Pa-PDT treated cells. Interestingly, the Pa-PDT induced JNK activation showed inhibitory effect on MDR by the down-regulation of P-glycoprotein in R-HepG2 cells in a dose-dependent manner. In addition, significant reduction of tumor size was obtained in Pa-PDT treated R-HepG2-bearing nude mice with no significant damages in liver and heart. Conclusion In summary, our findings provided the first evidence that PDT could inhibit the MDR activity by down-regulating the expression of P-glycoprotein via JNK activation using pheophorbide a as the photosensitizer, and our work proved that Pa-PDT inhibited the growth of MDR hepatoma cells by mitochondrial-mediated apoptosis induction.

Byline: Siu-Kai Kong This paper examines the competitiveness of biotechnology in Japan with Porter's Diamond Model. Japan is an industrialised country markedly different from the ones in Western Europe and North America. Japan has shown a remarkable capacity for economic growth and the use and integration of technologies. Japan is developing its strength in biotechnology based on a strong traditional position in many classical biotechnology sectors such as food processing and bio-engineering in the fermentation industry. This background provides a solid foundation for the development of modern biotechnology. Based on secondary data such as government publications and independent reports, this paper looks at the strengths and weaknesses of biotechnology in Japan. We show here that the support from the Japanese government has played a major role in the development of biotechnology. The clear long-term vision from the government shapes the goals of investors, managers and employees through various policies. The Japanese government has also stimulated a growth in R&D in universities and research centres and which has led to a close collaboration between industry and academia. The contribution from private sectors is also enormous. About 80% of the R&D resources are sourced from individual companies. To study the whole picture of biotechnology in Japan, Porter's Diamond Model provides a good and thorough basis to dissect how the Japanese biotechnology industry acquires global competitiveness. Although Japan still lags behind the USA in the area of biotechnology, the Japanese have been carrying out an extremely well coordinated effort to excel in this field. Japan will intensify her successful approaches learned from other industries to push ahead the development of biotechnology. It is conceivable that it will become more and more difficult for the Western counterparts to compete with this well organised and systematic Japanese approach in biotechnology.