Photodynamic therapy (PDT) is widely known as a promising treatment for malignant tumors. Hence new potent photosensitizers are extensively explored. Photosensitizers generally show strong aggregation tendency so that the photodynamic effects are significantly reduced under high concentration. A macromolecular polymeric micelle is a nanoparticle formed from several dozens of amphipathic polymers. Micelle has the properties of accumulating in tumors and escaping from traps in the liver, spleen and kidney. Thus, the nanoparticles permit tumor-selective drug delivery. We are aiming to establish an effective PDT for cancers by developing a nanoscaled drug delivery system (DDS) using photoreactive macromolecular micelles. Preliminarily we confirmed that PDT using the micelle-based DDS provided excellent anti-tumor effects, suggesting that this therapeutic strategy is expected to become a promising method.

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The ablation of stratum corneum (SC) by the pulsed-laser irradiation is one of the method to enhance the drug penetration in transdermal drug delivery system (TDDS). In this study, we have tried to enhance the drug penetration without the ablation of SC using 6μm-FELs. Lidocaine was used as the drug on this study. The enhancement of lidocaine penetration was measured by HPLC (High Performance Liquid chromatography). As results, the skin samples irradiated with FEL had the SC on the skin surface, the thermal relaxation times of the skin samples on 6-μm region were shorter than the macropulsese of FEL, 15μsec, because the skin samples were given the efficient thermal effect by the laser irradiation. It read to the enhancement of TDDS. The Lidocaine flux (mg/cm²/h) at 0.5 hour with the irradiated skin using an FEL was enhanced 10 fold faster than with the non-irradiated skin. We have demonstrated the effectiveness of an MIR-FEL (6-μm wavelength) irradiation in the TDDS. In conclusion, the skin samples were enhanced without the SC removal by the laser irradiation of the absorption peak of amide region in the skin sample.

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We developed new lamp light sources for photodynamic diagnosis (PDD) and evaluated their optical characterization. The lamp light sources were produced using lamps including mercury gas with and without metal halide such as gallium iodide, potassium iodide, or rubidium iodide into their discharge tube. These lamp light sources are abbreviated as Hg lamp, Ga lamp, K lamp, and Ru lamp. The fluence rate in 405±10 nm of Hg lamp (input power: 150 W) was the greatest among the lamp light sources and was about 10 times as high as that of a xenon lamp light source (input power 300 W), which have been used for PDD in medical treatments. Furthermore, the fluorescence intensity of protoporphyrin IX (PpIX) photoexited with Hg lamp was quite larger than that with any other lamps. This tendency was associated with the result from absorption photon energy of PpIX solution for the irradiation light from the lamps. When applying Hg lamp for PDD of a brain tumor in human brain tumor patient's extraction using 5-aminolevulinic acid-induced PpIX, moreover, we could observe red fluorescence emitted only from malignant brain tumor tissues by naked eyes. Consequently, Hg lamp produced in this study may be clinically effective for PDD in malignant brain tumor extraction.

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We investigated the fragmentation behavior of peptides and oligosaccharides using infrared multiple photodissociation (IRMPD) with a tunable IR free electron laser (FEL) in conjunction with Fourier-Transform Ion Cyclotron Resonance (FTICR) mass spectrometry (MS). The target ions of a protonated peptide (angiotensin II), protonated and sodiated saccharides (Lewis Y) were ionized by nano-electron spray ionization (ESI). The fragmentation behavior of these precursor ions was probed by monitoring the fragmentation of the ions induced by IRMPD in the IR wavelength range of 5.7-9.5μm. The results show that an abundance of the product ions from the peptide was mainly observed at 6.1μm, corresponding to the amide I band; these predominated due to contributions from the C = O stretching vibration of the peptide backbone. In the protonated ion of Lewis Y, the intensity of the fragment ions gradually increased on increasing the wavelength from 8.5μm. The curves for intensity peaked at a wavelength of around 9.1μm.

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The present study was to obtain an insight into the effects of different wavelengths on dentin. The absorption wavelength was selected based on the infrared absorption wavelength characteristics of dentin. IR-FEL beams of different wavelengths were irradiated on the sound or the decalcified dentin group with the irradiation energy density kept constant in order to examine the removed depth of and the morphologic change in dentin.
The following results were obtained. In the sound group, a two-fold eliminated depth was observed at wavelength 9.4μm compared with that of wavelength 6.4μm. On the other hand, in the decalcified group, relatively similar removed depth were observed at the points of wavelengths 9.4 and 6.4μm. Observation of the dentin surface under a SEM after laser irradiation showed that the surface layer of decalcified dentin was removed at wavelength 6.4μm, for some objects, which resulted in images in which the structures of Tomes fibers became obvious. At wavelength 9.4μm, unevenness was more noticeable on the dentin surface in the sound group compared with that in the decalcified group. At wavelength 10.6μm, no change was observed.

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Laser wavelength and pulse width are important parameters for next-generation laser treatment on cell and bimolecular. Free electron laser (FEL) is a powerful tool for novel laser diagnosis and therapy because it can be tuned wavelength at infrared region. In addition, FEL has a unique pulse structure, and the interaction to biological molecule can be controlled. This article introduces medical and biological researches by FEL at Osaka University.

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