This study presents a rapid photosensitizer-free method for trans-cis photoisomerization of carotenoids using nanosecond-pulsed laser irradiation. Pulsed laser irradiation enhanced the apparent dissolved fraction of β-carotene, astaxanthin, and lycopene suspended in organic solvents more significantly than continuous-wave irradiation. This was due to the formation of cis isomers, as evidenced by the appearance of multiple peaks in the chromatograms. The isomerization efficiency exhibited a quadratic dependence on light intensity, indicating a two-step photon absorption process. Optimal wavelengths for photoisomerization were 58-82 nm longer than the all-trans absorption maxima, suggesting the involvement of triplet states. Temporal analysis revealed a rapid decrease in the all-trans ratio, plateauing within 5 min under high-intensity conditions, and the cis-isomer content reached 89.3 ± 0.5% for β-carotene. These findings provide mechanistic insights into trans-cis photoisomerization and demonstrate a clean and efficient approach for producing cis-isomer-rich carotenoids, offering potential applications in functional foods, cosmetics, and pharmaceuticals.

Protein aggregates cause abnormal states and trigger various diseases, including neurodegenerative disorders. This study examined whether the xanthene dye derivative Rose Bengal could track a series of conformational changes in protein aggregates. Using lysozyme as a model protein, aggregated proteins were prepared by heating under acidic conditions. The absorption spectra, steady-state fluorescence spectra, fluorescence quantum yield, fluorescence lifetime, and phosphorescence lifetime of a solution containing Rose Bengal in the presence of aggregated lysozyme were measured to identify their spectroscopic characteristics. The absorption spectrum of Rose Bengal changed significantly during the formation of agglomerates in heated lysozyme. Additionally, the fluorescence intensity decreased during the initial stages of the aggregation process with an increase in heating time, followed by an increase in intensity along with a red-shift of the peak wavelength. The decrease in quantum yield with a fixed fluorescence lifetime supported the formation of a nonfluorescent ground-state complex between Rose Bengal and the aggregated lysozyme. Based on the characteristic changes in absorption and fluorescence properties observed during the aggregation process, Rose Bengal is considered an excellent indicator for the sensitive discernment of aggregated proteins.

The antitumor drug paclitaxel has low water solubility, and its bioavailability is limited by the dissolution rate. To overcome this low water solubility, the currently marketed drug, Taxol, is formulated in a vehicle including Cremophor EL and ethanol mixture (1/1, v/v). However, Cremophor EL has been shown to have serious adverse side effects, such as hypersensitivity reactions and neurotoxicity. Improving the solubility of paclitaxel makes it possible to reduce side effects and enhance drug efficacy during antitumor therapy. One way to improve the solubility of poorly soluble drugs is to decrease their particle size to the nano-range to increase the surface area and dissolution rate. In the present study, we aimed to develop a new method for paclitaxel nanoparticle production. Polymeric nanoparticles of paclitaxel were prepared by laser irradiation at 1064 nm, which is the wavelength in the near-IR region. The prepared nanoparticles had a mean size of 57.9 nm and were spherical in shape. X-ray powder diffraction analysis showed that paclitaxel in the nanoparticles was in an amorphous state. These results demonstrate that the preparation of nanoparticles by laser irradiation is effective in improving the solubility of paclitaxel. Furthermore, the nanoparticles had an equivalent efficacy to Taxol in cell growth inhibition against breast cancer MCF-7 cells and drug efficacy in MCF-7 tumor-bearing mice as determined using positron emission tomography. Our method for preparing paclitaxel nanoparticles may be more effective in treating tumors with fewer adverse side effects than conventional Taxol.

The responses of live cells to mid-infrared lasers may include the cell death, protein folding, ionic change, and so on and we have previously reported a preliminary result implying a substantial modulation in Ca2+ concentration in live HeLa cells by mid-infrared irradiation. In this presentation, in order to explore the effect of the Ca2+ change in depth, we specifically report the reactions of the neuronal cells irradiated with mid-infrared lasers. A quantum cascade laser (Hamamatsu) whose wavelength was 6.1 μm, corresponding to the “amide I” was adopted as an irradiation lightsource. The NG108-15 (ECACC) cells which are hybrid cells derived from nervous system were used as a sample. We have built a homemade upright fluorescent microscope with a scientific CMOS camera (Hamamatsu) which records the images at 100 fps, and the samples were irradiated by the mid-infrared laser from the bottom. Calcium concentrations and membrane potentials were labelled by fluorescent dyes. We have confirmed that the Ca2+ concentrations in the NG108-15 cells were modulated by the infrared laser irradiation. The threshold for the transient surge of Ca2+ was 9.7 mW, while 12.8 mW of the irradiation has elevated the Ca2+ concentrations permanently. The response in the membrane potentials showed a trend implying the threshold around 10m W which is similar to the Ca2+. But interestingly, some of the cells started to show more action potentials while some others stopped firing after the irradiation. We are trying to find the detailed criteria of the no-change, promotion, and inhibition in the action potentials correlated to the mid-infrared irradiation. In this study, we found that mid-infrared irradiation affects the membrane potentials of neuron-like cells. However, further verification is required for quantification of the irradiation criteria to reproducibly control the neuron-like cells’ firing.

We demonstrate the continuous multispectral imaging of surface phonon polaritons (SPhPs) on silicon carbide excited by an external cavity quantum cascade laser using scattering-type scanning near-field optical microscopy. The launched SPhPs were well characterized via the confirmation that the theoretical dispersion relation and measured in-plane wave vectors are in excellent agreement in the entire measurement range. The proposed scheme, which can excite and observe SPhPs with an arbitrary wavelength that effectively covers the spectral gap of CO2 lasers, is expected to be applicable for studies of near-field optics and for various applications based on SPhPs. (C) 2018 The Japan Society of Applied Physics

Nanonization, which involves the formation of the drug with nanometer particle size, is an effective method to improve the dissolution rate and bioavailability of poorly water-soluble drugs. A pulsewidth-tunable femtosecond laser was used to produce nanoparticles of clobetasone butyrate using poloxamer 188as stabilizing agent. The effects of temperature and pulsewidth on the particle size and concentration were studied for the first time. The particle size and drug concentration dependence on the laser intensity and irradiation time were also investigated. Permeability test releaved that laser nanonization improved the drug permeability across Caco-2 cell monolayer. This laser nanonization method has a great potential to be used for new drug development.

Terahertz pulsed spectroscopy has recently been demonstrated to be a novel technique for the investigation of the solid-state properties of pharmaceutical materials. In this study, we directly measured the crystallinity of a drug suspended in water, using a terahertz pulsed attenuated total reflection (ATR) method. The dihydropyridine calcium channel blocker nifedipine is classified as a poorly soluble drug; its most stable crystalline form is known as form I. Transmission spectra, collected from 0.2 to 2.0 THz (6.6 to 66 cm(-1) ), of nifedipine crystals had a strong absorption peak at 1.2 THz (40 cm(-1) ) at room temperature. When the nifedipine crystals were mixed with poloxamer 188 and suspended in water, the resulting spectra measured using the ATR method had a peak at the same frequency as in the spectra obtained in transmission mode. Furthermore, the peak area was proportional to the amount of crystals. The upward sloping baseline in the spectra, corresponding to water absorption, decreased stepwise with increasing amounts of crystalline particles. We confirmed that the spectra gave excellent quantitative results, using partial least-squares regression analysis. The results suggest the possibility of using this method for qualitative and quantitative assessments of crystalline drugs in suspension.

Nanoparticle formation of poorly water-soluble drugs is a means of providing much benefit for improving solubility and bioavailability. We showed that laser irradiation of drugs can be a novel tool for dispersing drug nanoparticles in water. Using our method, we were able to produce nanoparticles containing immunosuppressant drug, cyclosporin A, which shows poor solubility toward water, with high levels of the drug using polyvinyl pyrrolidone and sodium dodecyl sulfate as stabilizing agents. The absence of degradation products was confirmed and the loss of pharmaceutical activity with an inhibitory effect on the interleukin-2 production of Jurkat T cells did not occur. Cyclosporin A nanoparticles showed a spherical shape and their particle size was distributed uniformly around 200 nm. Powder X-ray diffraction analysis suggested that cyclosporin A in the nanoparticles was in an amorphous state. In the measurement of solubility rate, the nanoparticle formulation showed a higher rate than that which had not been processed. At present, although this laser irradiation technology has low productivity, it is expected as a new technology for drug nanoparticle manufacturing together with the development of a new laser device.

4-Hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) are well-known toxic products of lipid peroxidation. Phosphatidylcholine aldehydes are also known as oxidation products of phosphatidylcholine. The mechanism of the formation of these compounds in vivo has been a long-standing question. We observed that the rapid reaction of hemoproteins (methemoglobin, metmyoglobin, and cytochrome c) with 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH), having a hydroperoxylinoleoyl residue, generated HNE, MDA, and the phosphatidylcholine aldehyde 1-palmitoyl-2-(9-oxononanoyl) phosphatidylcholine. The efficiencies (mol% yield) of the formation of HNE and MDA from decomposed PLPC-OOH by methemoglobin, metmyoglobin, and cytochrome c after incubation for 10 min were 1.6, 1.0, and 1.0% for HNE and 1.2, 0.6, and 0.9% for MDA, respectively. When 1-palmitoyl-2-linoleoyl phosphatidylcholine was incubated with lipoxidase and methemoglobin, the formation of HNE and the phosphatidylcholine aldehyde 1-palmitoyl-2-(9-oxononanoyl) phosphatidylcholine was observed. When 1-palmitoyl-2-arachidonyl phosphatidylcholine was used instead of 1-palmitoyl-2-linoleoyl phosphatidylcholine, the phosphatidylcholine aldehyde 1-palmitoyl-2-oxovaleroyl phosphatidylcholine was obtained. These data suggest that HNE and phosphatidylcholine aldehydes might be rapidly formed from phosphatidylcholine by lipoxygenase and hemoproteins. Furthermore, hemichrome, converted from methemoglobin by deoxycholic acid and ursodeoxycholic acid, showed marked decomposition of HNE. These results suggest that hemoproteins are related to both the formation and the decomposition of HNE.

Yoshiro SAITO*†1, Noriko SATO*1, Masaki HIRASHIMA‡1, Gen TAKEBE*, Shigeharu NAGASAWA* and Kazuhiko TAKAHASHI*2 *Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan, †Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan, and ‡The Chemo-Sero-Therapeutic Research Institute, Kawabe, Kyokushi, Kikuchi-gun, Kumamoto 869-1298, Japan