研究者紹介システム

森田 健太
モリタ ケンタ
大学院工学研究科 応用化学専攻
助教
応用化学関係
Last Updated :2022/06/28

研究者情報

所属

  • 【主配置】

    大学院工学研究科 応用化学専攻
  • 【配置】

    工学部 応用化学科, 先端膜工学研究センター

学位

  • 博士(工学), 神戸大学

研究活動

研究キーワード

  • 高分子
  • 界面
  • 電子顕微鏡
  • 生体材料
  • ナノ材料
  • ペプチド
  • 過酸化チタン
  • がん
  • 放射線治療
  • ナノ粒子

研究分野

  • ナノテク・材料 / 複合材料、界面

受賞

  • 2022年05月 高分子学会, 高分子学会広報委員会パブリシティ賞, がん細胞の内部をゲル化してアポトーシス死を導くペプチド型抗がん剤の開発

    森田 健太, 西村 香音, 山本 翔太, 清水 なつみ, 青井 貴之, 田村 厚夫, 丸山 達生

  • 2021年08月 株式会社ストラテジック, IRMAILサイエンスグラント 横河電機賞, がん細胞を"内側から固めて"殺す自己組織化ペプチド薬の抗がん作用機序の実証

    森田健太

論文

  • Shota Yamamoto, Kanon Nishimura, Kenta Morita, Sayuki Kanemitsu, Yuki Nishida, Tomoyuki Morimoto, Takashi Aoi, Atsuo Tamura, Tatsuo Maruyama

    Self-assembly of synthetic molecules has been drawing broad attention as a novel emerging approach in drug discovery. Here, we report selective cell death induced by a novel peptide amphiphile that self-assembles to form entangled nanofibers (hydrogel) based on intracellular pH (pHi). We found that a palmitoylated hexapeptide (C16-VVAEEE) formed a hydrogel below pH 7. The formation of the nanofibrous self-assembly was responsive to a small pH change around pH 7. The cytotoxicity of C16-VVAEEE was correlated with pHi of cells. Microscope observation demonstrated the self-assembly of C16-VVAEEE inside HEK293 cells. In vivo experiments revealed that the transcutaneous administration of C16-VVAEEE showed remarkable anti-tumor activity. This study proposes that distinct microenvironment inside living cells can be used as a trigger for the intracellular self-assembly of a peptide amphiphile, which provide a new clue to drug discovery.

    AMER CHEMICAL SOC, 2021年06月, BIOMACROMOLECULES, 22 (6), 2524 - 2531, 英語, 国際誌

    研究論文(学術雑誌)

  • Kenta Morita, Shinano Takeda, Ayumi Yunoki, Takane Tsuchii, Tsutomu Tanaka, Tatsuo Maruyama

    We propose a novel approach to prepare affinity membranes using azido-containing surfactants and click chemistry. Porous polymeric membranes were prepared using cellulose acetate via polymer phase separation in the presence of azido-containing surfactants. Thermally induced phase separation and nonsolvent-induced phase separation were used for membrane preparation. The azido groups displayed on the membrane surfaces were conjugated with nitrilotriacetic acid via Huisgen 1,3-dipolar cycloaddition to prepare membranes that displayed affinity toward a hexahistidine-tagged protein. Two types of phase separation successfully produced porous membranes with different microstructures but showed similar separation performances. In place of nitrilotriacetic acid, D-Ala-D-Ala was conjugated to the surface of the azido-functionalized membrane. The membranes functionalized with D-Ala-D-Ala showed high affinity toward vancomycin. The present approach leads to facile surface functionalization of polymeric materials and produces affinity membranes displaying various types of ligands on their surfaces.

    ELSEVIER, 2021年02月, COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, 611, 英語

    研究論文(学術雑誌)

  • Kenta Morita, Yuya Nishimura, Satoko Nakamura, Yuki Arai, Chiya Numako, Kazuyoshi Sato, Masao Nakayama, Hiroaki Akasaka, Ryohei Sasaki, Chiaki Ogino, Akihiko Kondo

    Polyacrylic acid-modified titanium peroxide nanoparticles (PAA-TiOx NPs) are promising radiosensitizers that enhance the therapeutic effect of X-ray irradiation after local injection into tumors. However, the mechanism for this reaction has remained unclear with the exception of the involvement of hydrogen peroxide (H2O2), which is released by PAA-TiOx NPs to a liquid phase during dispersion. In the present study, a clonogenic assay was used to compare PAA-TiOx NPs with free H2O2 molecules to investigate the effect exerted on the radiosensitivity of cancer cells in vitro. A cell-free dialysis method revealed that a portion of the H2O2 adsorbed onto the PAA-TiOx NPs during synthesis could be released during a treatment regimen. The H2O2 release lasted for 7 h, which was sufficient for one radiation treatment procedure. For in vitro experiments, cultured human pancreatic cancer cells took up PAA-TiOx NPs in 10 min after administration. Interestingly, when the cells were washed with a buffer after treatment with either a PAA-TiOx NP or H2O2 solution, the intracellular H2O2 levels remained higher with PAA-TiOx NP treatment compared with the H2O2 solution treatment. Furthermore, the effects of subsequent X-ray irradiation corresponded to the intracellular H2O2 levels. These results indicate that PAA-TiOx NPs are efficient carriers of H2O2 into cancer cells and thus enhance the radiosensitivity.

    ELSEVIER, 2021年02月, COLLOIDS AND SURFACES B-BIOINTERFACES, 198, 英語

    研究論文(学術雑誌)

  • Yasuyuki Nakamura, Ririka Asama, Takuya Tabata, Kenta Morita, Tatsuo Maruyama, Akihiko Kondo, Jun Ishii

    Melatonin is an indoleamine neurohormone made by the pineal gland. Its receptors, MTNR1A and MTNR1B, are members of the G-protein-coupled receptor (GPCR) family and are involved in sleep, circadian rhythm, and mood disorders, and in the inhibition of cancer growth. These receptors, therefore, represent significant molecular targets for insomnia, circadian sleep disorders, and cancer. The yeast Saccharomyces cerevisiae is an attractive host for assaying agonistic activity for human GPCR. We previously constructed a GPCR-based biosensor employing a high-sensitivity yeast strain that incorporated both a chimeric yeast-human G alpha protein and a bright fluorescent reporter gene (ZsGreen). Similar approaches have been used for simple and convenient measurements of various GPCR activities. In the current study, we constructed a fluorescence-based yeast biosensor for monitoring the signaling activation of human melatonin receptors. We used this system to analyze point mutations, including previously unreported mutations of the consensus sequences of MTNR1A and MTNR1B melatonin receptors and compared their effects. Most mutations in the consensus sequences significantly affected the signaling capacities of both receptors, but several mutations showed differences between these subtype receptors. Thus, this yeast biosensor holds promise for revealing the functions of melatonin receptors.

    WILEY, 2021年02月, BIOTECHNOLOGY AND BIOENGINEERING, 118 (2), 863 - 876, 英語

    研究論文(学術雑誌)

  • Yuya Nishimura, Ryosuke Ezawa, Kenta Morita, Masao Nakayama, Jun Ishii, Ryohei Sasaki, Chiaki Ogino, Akihiko Kondo

    Radiosensitizing therapy for cancer treatment that enhances the effect of existing radiation therapy and enables noninvasive therapy has attracted attention. In this study, to achieve target cell-specific noninvasive cancer treatment using a Z(HER2)-bionanocapsule/liposome (BNC/LP), a carrier that binds to human epidermal growth factor receptor 2 (HER2), we evaluated the delivery of anticancer drugs and radiosensitizers and treatment effects in vitro and in vivo in mice. Target cell-specific cytotoxic activity and antitumor effects were confirmed following delivery of doxorubicin-encapsulated particles. In addition, cell damage due to radiosensitizing effects was confirmed in combination with X-ray irradiation following delivery of particles containing polyacrylic acid-modified titanium peroxide nanoparticles as a radiosensitizer. Furthermore, even when the particles were injected via the tail vein of mice, they accumulated in the tumor and exhibited an antitumor effect because of radiosensitization. Therefore, Z(HER2)-BNC/ LP is expected to be a carrier that releases small-molecule drugs into the target cell cytoplasm and delivers a radiosensitizer such as inorganic nanoparticles, enabling combination therapy with X-rays to the target tumor.

    AMER CHEMICAL SOC, 2020年11月, ACS APPLIED BIO MATERIALS, 3 (11), 7743 - 7751, 英語

    研究論文(学術雑誌)

  • Emmanuel Quayson, Jerome Amoah, Nova Rachmadona, Kenta Morita, Lawrence Darkwah, Shinji Hama, Ayumi Yoshida, Akihiko Kondo, Chiaki Ogino

    Continuous expansion of agriculture for the production of biofuels may be considered a potential source of greenhouse gas (GHG) emissions due to the ever-increasing amount of waste and fossil fuel-dependent materials involved. Agricultural waste utilization through the circular bioeconomy concept offers a pathway to reduce GHG emissions. Palm oil production, for instance, produces palm kernel shells (PKS) and palm oil mill effluents (POME) as wastes in enormous amounts. PKS and POME account for >60% of solid and liquid waste generated from the mill. In this work, the feasibility of a circular palm bioeconomy is explored where waste PKS is directly converted to activated carbons (AC) in a cost-effective one-step technique (550 degrees C, 10 mL min(-1) N-2) that departs from the conventional two-step (carbonization and activation) technique. Characterization of the synthesized carbons, PKAC, using Fourier-transform infrared spectroscopy and scanning electron microscopy with energy-dispersive X-ray spectroscopy showed oxygen-rich morphological features that were 2-fold higher than in bituminous coal-derived AC. The <10 mu m pore diameters of PKAC were relevant in the immobilization of Aspergillus oryzae whole-cells expressing Fusarium heterosporum lipase (PKAC-FHL). For biodiesel production, the 81.6 IU mg(-1) specific activity of PKAC-FHL yielded >= 97.5 wt% fatty acid methyl ester (FAME) from POME. While offering the benefits of environmental remediation through effluent utilization, the produced FAME showed 48.8 Cetane Number and cold-flow properties that conform to ASTM and EN biodiesel requirements. This waste valorization approach, thus, proposes a green framework for the use of POME and PKS in immobilized lipase-catalyzed methanolysis.

    PERGAMON-ELSEVIER SCIENCE LTD, 2020年11月, BIOMASS & BIOENERGY, 142, 英語

    研究論文(学術雑誌)

  • Hiroaki Akasaka, Naritoshi Mukumoto, Masao Nakayama, Tianyuan Wang, Ryuichi Yada, Yasuyuki Shimizu, Sachiko Inubushi, Katsusuke Kyotani, Keisuke Okumura, Masanori Miyamoto, Ai Nakaoka, Kenta Morita, Yuya Nishimura, Chiaki Ogino, Ryohei Sasaki

    Nanoparticles (NPs) are useful for radiotherapy. Currently, efforts are underway globally for the development of novel titanium dioxide NPs (TiO2-NPs) that exhibit both contrast effects and anti-tumor effects. In this study, the image contrast properties of TiO2-NPs were evaluated using a clinical magnetic resonance imaging (MRI) system and a clinical computed tomography (CT) scanner, as the use of TiO2-NPs as an anti-cancer agent has been reported in several reports. An obvious difference in visualization was observed between the control and TiO2-NP samples onT(2)-weighted images. These results suggest that TiO(2)can potentially be used as a novel theranostic drug with radiosensitizing ability and radiological diagnostic ability, through modification of chemical groups on its surface, and as a component of drug delivery systems.

    SPRINGER HEIDELBERG, 2020年08月, APPLIED NANOSCIENCE, 10 (8), 3143 - 3148, 英語

    研究論文(学術雑誌)

  • Masao Nakayama, Clare L. Smith, Bryce N. Feltis, Terrence J. Piva, Farnaz Tabatabaie, Peter D. Harty, Frank M. Gagliardi, Kirsten Platts, Sarah Otto, Anton Blencowe, Kenta Morita, Moshi Geso

    Purpose: Titanium dioxide nanoparticles (TiO2 NPs) have been investigated for their role as radiosensitisers for radiation therapy. The study aims to increase the efficiency of these NPs by synthesising them with samarium.Methods: Samarium-doped TiO2 NPs (Ti(Sm)O-2 NPs) were synthesised using a solvothermal method. Transmission electron microscopy (TEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS) were performed for characterising of the Ti(Sm)O-2 NPs. The intracellular uptake and cytotoxicity were assessed in vitro using A549 and DU145 cancer cell lines. Furthermore, the effect of dose enhancement and generation of reactive oxygen species (ROS) in response to 6 MV X-rays was evaluated. Additionally, the image contrast properties were investigated using computed tomography (CT) images.Results: The synthesised Ti(Sm)O-2 NPs were about 13 nm in diameter as determined by TEM. The XRD pattern of Ti(Sm)O-2 NPs was consistent with that of anatase-type TiO2. EDS confirmed the presence of samarium in the nanoparticles. At 200 mu g/ml concentration, no differences in cellular uptake and cytotoxicity were observed between TiO2 NPs and Ti(Sm)O-2 NPs in both A549 and DU145 cells. However, the combination of Ti(Sm)O-2 NPs and X-rays elicited higher cytotoxic effect and ROS generation in the cells than that with TiO2 NPs and X-rays. The CT numbers of Ti(Sm)O-2 NPs were systematically higher than that of TiO2 NPs.Conclusions: The Ti(Sm)O-2 NPs increased the dose enhancement of MV X-ray beams than that elicited by TiO2 NPs. Samarium improved the efficiency of TiO2 NPs as potential radiosensitising agent.

    ELSEVIER SCI LTD, 2020年07月, PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS, 75, 69 - 76, 英語

    研究論文(学術雑誌)

  • Mennaallah Hassan, Masao Nakayama, Mohammed Salah, Hiroaki Akasaka, Hikaru Kubota, Makiko Nakahana, Tatsuichiro Tagawa, Kenta Morita, Ai Nakaoka, Takeaki Ishihara, Daisuke Miyawaki, Kenji Yoshida, Yuya Nishimura, Chiaki Ogino, Ryohei Sasaki

    The development of potentially safe radiosensitizing agents is essential to enhance the treatment outcomes of radioresistant cancers. The titanium peroxide nanoparticle (TiOxNP) was originally produced using the titanium dioxide nanoparticle, and it showed excellent reactive oxygen species (ROS) generation in response to ionizing radiation. Surface coating the TiOxNPs with polyacrylic acid (PAA) showed low toxicity to the living body and excellent radiosensitizing effect on cancer cells. Herein, we evaluated the mechanism of radiosensitization by PAA-TiOxNPs in comparison with gold nanoparticles (AuNPs) which represent high-atomic-number nanoparticles that show a radiosensitizing effect through the emission of secondary electrons. The anticancer effects of both nanoparticles were compared by induction of apoptosis, colony-forming assay, and the inhibition of tumor growth. PAA-TiOxNPs showed a significantly more radiosensitizing effect than that of AuNPs. A comparison of the types and amounts of ROS generated showed that hydrogen peroxide generation by PAA-TiOxNPs was the major factor that contributed to the nanoparticle radiosensitization. Importantly, PAA-TiOxNPs were generally nontoxic to healthy mice and caused no histological abnormalities in the liver, kidney, lung, and heart tissues.

    MDPI, 2020年06月, NANOMATERIALS, 10 (6), 英語

    研究論文(学術雑誌)

  • Masao Nakayama, Hiroaki Akasaka, Moshi Geso, Kenta Morita, Ryuichi Yada, Kazuyuki Uehara, Ryohei Sasaki

    Gold nanoparticles (AuNPs) are being investigated extensively for their role as radiosensitisers. Studies have shown that they are effective dose enhancing agents. One of the main factors that enables AuNPs to function as dose enhancing agents is their ability to generate reactive oxygen species under X-ray irradiation. In this study, we investigated this issue utilising a chemiluminescence technique with 3'-(p-aminophenyl) fluorescein (APF) in a phantom. First, we examined the time variation and dose response of the fluorescence intensity of APF for spherical 50 nm AuNPs exposed to a 6 MV photon beam. The APF reagent was added to the AuNPs suspension in a small tube fixed in a water phantom. The fluorescence intensities of APF were measured using a microplate reader. Next, based on the APF response, we evaluated the dose enhancements caused by AuNPs in a 6 MV flattening filter (FF) and flattening filter-free (FFF) photon beams and doses of either 2, 4, or 6 Gy. While the time variation of APF fluorescence intensity without AuNPs was less than 5% after X-ray irradiation, we observed an increase in the fluorescence intensity over time in the presence of AuNPs without the radiation. The APF signals had a linear response to X-ray irradiation in a dose-dependent manner. The measured dose enhancement ratios for the FFF beam were significantly higher than that for the FF beam in the presence of 30 mu g/ml AuNPs. This result shows APF can successfully detect differences in dose enhancement between the FF and FFF beams using AuNPs. In conclusion, the chemiluminescence technique using APF is a useful and simple method to estimate the level of dose enhancement caused by nanoparticles in a phantom.

    PERGAMON-ELSEVIER SCIENCE LTD, 2020年06月, RADIATION MEASUREMENTS, 134, 英語

    研究論文(学術雑誌)

  • Takeshi Nagase, Tomoyuki Terai, Tomoyuki Kakeshita, Kenta Morita

    The rapid solidification microstructure and magnetic properties of melt-spun ribbons in Ag52Cu23.2La4.8Fe20 (at%) alloy, which was designed as the combination of Ag-rich Ag65Cu29La6 alloy with high glass-forming ability (GFA) and Fe, were investigated. An amorphous phase formation was observed in a melt-spun ribbon of ternary Ag65Cu29La6 alloy. The composite of Ag-Cu-based crystalline matrix and BCC-Fe globules was obtained in Ag52Cu23.2La4.8Fe20 alloy. The size of BCC-Fe globules embedded in an Ag-Cu-based crystalline matrix was on the order of 50 nm. The Fe addition deteriorated the GFA in Ag-rich Ag-Cu-La alloys. The combination of liquid-phase separation and stabilization of liquid for amorphous phase formation during rapid cooling leads to the formation of the particular solidification microstructure in Ag-rich Ag-Cu-La-Fe immiscible alloy. The melt-spun ribbon shows typical ferromagnetic magnetic properties due to the 50-nm BCC-Fe globules.

    JAPAN INST METALS & MATERIALS, 2020年, MATERIALS TRANSACTIONS, 61 (2), 311 - 317, 英語

    研究論文(学術雑誌)

  • Manami Hara, Shigeru Kitahata, Keisuke Nishimori, Koki Miyahara, Kenta Morita, Kaya Tokuda, Takashi Nishino, Tatsuo Maruyama

    NATURE PUBLISHING GROUP, 2019年12月, POLYMER JOURNAL, 51 (12), 1309 - 1310, 英語

  • Gregory G. Y. Guirimand, Takahiro Bamba, Mami Matsuda, Kentaro Inokuma, Kenta Morita, Yuki Kitada, Yuma Kobayashi, Takahiro Yukawa, Kengo Sasaki, Chiaki Ogino, Tomohisa Hasunuma, Akihiko Kondo

    Xylitol is a highly valuable commodity chemical used extensively in the food and pharmaceutical industries. The production of xylitol from d-xylose involves a costly and polluting catalytic hydrogenation process. Biotechnological production from lignocellulosic biomass by micro-organisms like yeasts is a promising option. In this study, xylitol is produced from lignocellulosic biomass by a recombinant strain of Saccharomyces cerevisiae (S. cerevisiae) (YPH499-SsXR-AaBGL) expressing cytosolic xylose reductase (Scheffersomyces stipitis xylose reductase [SsXR]), along with a beta-d-glucosidase (Aspergillus aculeatus beta-glucosidase 1 [AaBGL]) displayed on the cell surface. The simultaneous cofermentation of cellobiose/xylose by this strain leads to an approximate to 2.5-fold increase in Yxylitol/xylose (=0.54) compared to the use of a glucose/xylose mixture as a substrate. Further improvement in the xylose uptake by the cell is achieved by a broad evaluation of several homologous and heterologous transporters. Homologous maltose transporter (ScMAL11) shows the best performance in xylose transport and is used to generate the strain YPH499-XR-ScMAL11-BGL with a significantly improved xylitol production capacity from cellobiose/xylose coutilization. This report constitutes a promising proof of concept to further scale up the biorefinery industrial production of xylitol from lignocellulose by combining cell surface and metabolic engineering in S. cerevisiae.

    WILEY-V C H VERLAG GMBH, 2019年09月, BIOTECHNOLOGY JOURNAL, 14 (9), 英語

    研究論文(学術雑誌)

  • Quentin Schmetz, Hiroshi Teramura, Kenta Morita, Tomoko Oshima, Aurore Richel, Chiaki Ogino, Akihiko Kondo

    An organosolv pretreatment consisting of an H2SO4/n-butanol biphasic system was designed to separate lignocellulosic biomass in three distinct phases: a cellulose-rich solid residue, hydrolyzed hemicelluloses in an aqueous phase, and lignin dissolved in a hydrophobic butanol phase. In the present study, the versatility of the process was investigated on materials of various compositions and origins: sugar cane bagasse, tall fescue, sugar beet pulp, eucalyptus, beech, and Japanese cedar. The efficiency was assessed in terms of lignin removal from the raw biomass and purity of the recovered cellulosic residue using the Klason method as well as improvement on enzymatic saccharification (increased from 18.7% to 96%). Results were correlated to biomass types and composition, and in comparison to an organic solvent-free method (dilute acid). Up to 81% cellulose purity corresponding to 87% lignin removal was achieved. Results were corroborated by scanning electron microscopy showing an absence of lignin deposition. Lignin molecular weight (GPC), structure (2D-HSQC NMR), recovery, and purity (up to 96%) have been investigated. Moreover, organic compounds responsible for fermentation inhibition were partially solubilized in the butanol, decreasing the concentration in the aqueous phase. Efficient butanol pretreatment applied on hardwood, bagasse, and herbaceous matter is promising. However, Japanese cedar (softwood) was for this process,

    AMER CHEMICAL SOC, 2019年07月, ACS SUSTAINABLE CHEMISTRY & ENGINEERING, 7 (13), 11069 - 11079, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Manami Hara, Shigeru Kitahata, Keisuke Nishimori, Koki Miyahara, Kenta Morita, Kaya Tokuda, Takashi Nishino, Tatsuo Maruyama

    Isotactic polypropylene (PP) is one of the most popular plastics. However, the remarkably low surface energy of PP prevents the surface functionalization of PP. We studied the surface functionalization of PP by dip-coating with a maleic anhydride-grafted chlorinated polypropylene (MPO)/methacrylate-based terpolymer mixture. A methacrylate-based terpolymer (PMFP) was synthesized, which contained perfluoroalkyl (R-f)-conjugated monomers and poly(ethylene glycol)-conjugated monomers. Tape-peeling tests revealed that MPO successfully immobilized PMFP on a PP surface, although PMFP was less adhesive to PP. X-ray photoelectron spectroscopy (XPS), contact angle, and protein adsorption measurements revealed that the R-f groups and PEG chains in PMFP were segregated to the outermost surface of the dip-coated layer. The surface segregation of these moieties produced a low-fouling surface on the PP substrate. In addition, we synthesized a terpolymer that contained R-f groups and PEG chains with carboxy groups at their termini (PMFB) and used it to dip-coat a PP substrate. The surface segregation of side chains in PMFB induced the presentation of carboxy groups at the outermost surface, which were used as reactive sites for enzyme immobilization.

    NATURE PUBLISHING GROUP, 2019年05月, POLYMER JOURNAL, 51 (5), 489 - 499, 英語

    研究論文(学術雑誌)

  • Gregory Guirimand, Kentaro Inokuma, Takahiro Bamba, Mami Matsuda, Kenta Morita, Kengo Sasaki, Chiaki Ogino, Jean-Guy Berrin, Tomohisa Hasunuma, Akihiko Kondo

    Xylitol is a major commodity chemical widely used in both the food and pharmaceutical industries. Although the worldwide demand for xylitol is constantly growing, its industrial production from purified D-xylose involves a costly and polluting catalytic hydrogenation process. Biotechnological production of xylitol from biomass is a promising strategy to establish an environmentally friendly sustainable conversion process. In this study, xylitol was produced from woody Kraft pulp (KP) by using an engineered strain of Saccharomyces cerevisiae (YPH499-XR-BGL-XYL-XYN) expressing cytosolic xylose reductase (XR), along with beta-D-glucosidase (BGL), xylosidase (XYL) and xylanase (XYN) enzymes co-displayed on the cell surface. All these enzymes contributed to the consolidated bioprocessing of KP to xylitol with a yield of 2.3 g L-1 (28% conversion) after 96 hours, along with a significantly reduced amount of commercial enzymes required for pre-treatment (commercial hemicellulase cocktail (CHC), [CHC] = 0.02 g-DW per g). Further improvement of the cell surface display of XYL and XYN was obtained by using a SED1 "SSS" cassette, containing the coding sequences of the SED1 promoter, the SED1 secretion signal, and the SED1 anchoring domain, to generate the improved strain YPH499-XR-BGL-XYLsss-XYNsss. This improved strain showed a significantly enhanced xylitol production capacity reaching a yield of 3.7 g L-1 (44% conversion) after 96 hours. The cellulosic content of KP residues was also significantly increased, from 78% to 87% after 96 hours of fermentation, and nanofibrillation of KP residues was observed by scanning electron microscopy. Pre-treatment and fermentation were successfully performed as a proof of concept to further scale up bio-refinery industrial production of xylitol from lignocellulose.

    ROYAL SOC CHEMISTRY, 2019年04月, GREEN CHEMISTRY, 21 (7), 1795 - 1808, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Emmanuel Quayson, Jerome Amoah, Shinji Hama, Ayumi Yoshida, Kenta Morita, Akihiko Kondo, Chiaki Ogino

    The biomass-derived source, low-cost and hydrophobicity/oleophilic advantages of activated carbon (AC) were explored for the immobilization of Aspergillus oryzae whole-cells expressing Fusarium heterosporum lipase. The adsorptive influence of AC favored growth of the cells into its porous interfaces with paralleled exterior dense film formation. Increasing AC weights hindered extracellular lipase activity. Cell aggregation of 0.34 +/- 0.02 mg/BSP was found to be effective in catalyzing an industrially challenging feedstock (68.77% w/w free fatty acids, 20.48% w/w triglycerides) to 98% fatty acid methyl esters (FAME). In a comparative investigation with polyurethane as matrix, higher trans/esterification facilitation was observed with AC. Benefiting from the oleophilicity of AC; denaturation effect from methanol on the lipases was reduced. Surface characterization with FE-SEM, XPS and FT-IR evidenced effective cell-matrix adhesion and a retention of the AC's intrinsic properties. The advantageous tribology of AC ensured recyclability of the matrix for fresh cells immobilization. Comparable FAME (98.08% w/w) was achieved with the recycled matrix in successive batches. The spent-matrix valorization approach, thus, proposes sustainable biorefineries with immobilized lipase catalyzed biodiesel production.

    AMER CHEMICAL SOC, 2019年03月, ACS SUSTAINABLE CHEMISTRY & ENGINEERING, 7 (5), 5010 - 5017, 英語

    研究論文(学術雑誌)

  • Kenta Morita, Serika Miyazaki, Chiya Numako, Shinya Ikeno, Ryohei Sasaki, Yuya Nishimura, Chiaki Ogino, Akihiko Kondo

    An induction of polyacrylic acid-modified titanium dioxide with hydrogen peroxide nanoparticles (PAA-TiO2/H2O2 NPs) to a tumor exerted a therapeutic enhancement of X-ray irradiation in our previous study. To understand the mechanism of the radiosensitizing effect of PAA-TiO2/H2O2 NPs, analytical observations that included DLS, FE-SEM, FT-IR, XAFS, and Raman spectrometry were performed. In addition, highly reactive oxygen species (hROS) which PAA-TiO2/H2O2 NPs produced with X-ray irradiation were quantified by using a chemiluminescence method and a EPR spin-trapping method. We found that PAA-TiO2/H2O2 NPs have almost the same characteristics as PAA-TiO2. Surprisingly, there were no significant differences in hROS generation. However, the existence of H2O2 was confirmed in PAA-TiO2/H2O2 NPs, because spontaneous hROS production was observed w/o X-ray irradiation. In addition, PAA-TiO2/H2O2 NPs had a curious characteristic whereby they absorbed H2O2 molecules and released them gradually into a liquid phase. Based on these results, the H2O2 was continuously released from PAA-TiO2/H2O2 NPs, and then released H2O2 assumed to be functioned indirectly as a radiosensitizing factor.

    TAYLOR & FRANCIS LTD, 2016年12月, FREE RADICAL RESEARCH, 50 (12), 1319 - 1328, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Masao Nakayama, Ryohei Sasaki, Chiaki Ogino, Tsutomu Tanaka, Kenta Morita, Mitsuo Umetsu, Satoshi Ohara, Zhenquan Tan, Yuya Nishimura, Hiroaki Akasaka, Kazuyoshi Sato, Chiya Numako, Seiichi Takami, Akihiko Kondo

    Background: Biological applications of nanoparticles are rapidly increasing, which introduces new possibilities to improve the efficacy of radiotherapy. Here, we synthesized titanium peroxide nanoparticles (TiOxNPs) and investigated their efficacy as novel agents that can potently enhance the effects of radiation in the treatment of pancreatic cancer.Methods: TiOxNPs and polyacrylic acid-modified TiOxNPs (PAA-TiOxNPs) were synthesized from anatase-type titanium dioxide nanoparticles (TiO(2)NPs). The size and morphology of the PAA-TiOxNPs was evaluated using transmission electron microscopy and dynamic light scattering. The crystalline structures of the TiO(2)NPs and PAA-TiOxNPs with and without X-ray irradiation were analyzed using X-ray absorption. The ability of TiOxNPs and PAA-TiOxNPs to produce reactive oxygen species in response to X-ray irradiation was evaluated in a cell-free system and confirmed by flow cytometric analysis in vitro. DNA damage after X-ray exposure with or without PAA-TiOxNPs was assessed by immunohistochemical analysis of gamma-H2AX foci formation in vitro and in vivo. Cytotoxicity was evaluated by a colony forming assay in vitro. Xenografts were prepared using human pancreatic cancer MIAPaCa-2 cells and used to evaluate the inhibition of tumor growth caused by X-ray exposure, PAA-TiOxNPs, and the combination of the two.Results: The core structures of the PAA-TiOxNPs were found to be of the anatase type. The TiOxNPs and PAA-TiOxNPs showed a distinct ability to produce hydroxyl radicals in response to X-ray irradiation in a dose-and concentration-dependent manner, whereas the TiO(2)NPs did not. At the highest concentration of TiOxNPs, the amount of hydroxyl radicals increased by >8.5-fold following treatment with 30 Gy of radiation. The absorption of PAA-TiOxNPs enhanced DNA damage and resulted in higher cytotoxicity in response to X-ray irradiation in vitro. The combination of the PAA-TiOxNPs and X-ray irradiation induced significantly stronger tumor growth inhibition compared to treatment with either PAA-TiOxNPs or X-ray alone (p < 0.05). No apparent toxicity or weight loss was observed for 43 days after irradiation.Conclusions: TiOxNPs are potential agents for enhancing the effects of radiation on pancreatic cancer and act via hydroxyl radical production; owing to this ability, they can be used for pancreatic cancer therapy in the future.

    BMC, 2016年07月, RADIATION ONCOLOGY, 11, 英語

    研究論文(学術雑誌)

  • Masao Nakayama, Ryohei Sasaki, Toru Mukohara, Chiaki Ogino, Kenta Morita, Mitsuo Umetsu, Satoshi Ohara, Kazuyoshi Sato, Chiya Numako, Seiichi Takami, Akihiko Kondo

    AMER ASSOC CANCER RESEARCH, 2015年08月, CANCER RESEARCH, 75, 英語

  • Izzat Fahimuddin Bin Mohamed Suffian, Yuya Nishimura, Kenta Morita, Sachiko Nakamura-Tsuruta, Khuloud T. Al-Jamal, Jun Ishii, Chiaki Ogino, Akihiko Kondo

    Background: The hepatitis B virus core (HBc) particle is known as a promising new carrier for the delivery of drugs and nucleic acids. However, since the arginine-rich domain that is located in the C-terminal region of the HBc monomer binds to the heparan sulphate proteoglycan on the cell surface due to its positive charge, HBc particles are introduced non-specifically into a wide range of cells. To avoid non-specific cellular uptake with the intent to control the ability of cell targeting, we individually replaced the respective arginine (R) residues of the arginine-rich domain located in amino acid positions 150-159 in glycine (G) residues.Results: The mutated HBc particles in which R154 was replaced with glycine (G) residue (R154G) showed a drastic decrease in the ability to bind to the heparan sulphate proteoglycan and to avoid non-specific cellular uptake by several types of cancer cells.Conclusions: Because this mutant particle retains most of its C-terminal arginine-rich residues, it would be useful in the targeting of specificity-altered HBc particles in the delivery of nucleic acids.

    BIOMED CENTRAL LTD, 2015年02月, JOURNAL OF NANOBIOTECHNOLOGY, 13, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Mohammed Salah, Hiroaki Akasaka, Yasuyuki Shimizu, Kenta Morita, Yuya Nishimura, Hikaru Kubota, Hiroki Kawaguchi, Tomomi Sogawa, Naritoshi Mukumoto, Chiaki Ogino, Ryohei Sasaki

    Background Despite recent advances in radiotherapy, radioresistance in patients with pancreatic cancer remains a crucial dilemma for clinical treatment. Cancer stem cells (CSCs) represent a major factor in radioresistance. Developing a potent radiosensitizer may be a novel candidate for the eradication of pancreatic CSCs. Methods CSCs were isolated from MIA PaCa-2 and PANC1 human pancreatic cancer cell lines. Titanium peroxide nanoparticles (TiOxNPs) were synthesized from titanium dioxide nanoparticles (TiO(2)NPs) and utilized as radiosensitizers when added one hour prior to radiation exposure. The antitumor activity of this novel therapeutic strategy was evaluated against well-established pancreatic CSCs model both in vitro and in vivo. Results It is shown that TiOxNPs combined with ionizing radiation exhibit anti-cancer effects on radioresistant CSCs both in vitro and in vivo. TiOxNPs exhibited a synergistic effect with radiation on pancreatic CSC-enriched spheres by downregulating self-renewal regulatory factors and CSC surface markers. Moreover, combined treatment suppressed epithelial-mesenchymal transition, migration, and invasion properties in primary and aggressive pancreatic cancer cells by reducing the expression of proteins relevant to these processes. Notably, radiosensitizing TiOxNPs suppressed the growth of pancreatic xenografts following primary or dissociating sphere MIA PaCa-2 cell implantation. It is inferred that synergy is formed by generating intolerable levels of reactive oxygen species (ROS) and inactivating the AKT signaling pathway. Conclusions Our data suggested the use of TiOxNPs in combination with radiation may be considered an attractive therapeutic strategy to eliminate pancreatic CSCs.

    BMC, 2022年04月, JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 41 (1), 英語

    研究論文(学術雑誌)

  • Takane Tsuchii, Kazuki Kaneko, Kenta Morita, Takashi Nishino, Tatsuo Maruyama

    Fluorous chemistry has unique features and high potential applicability, which are distinct from those of non-fluorinated organic compounds. However, there are limited reports detailing the applications of fluorous-fluorous interactions (fluorophilicity or fluorous affinity), likely because these interactions are not found in nature. In the present study, we describe the rewritable surface functionalization of a plastic substrate based on fluorous affinity. Plastic substrates were dip-coated with a series of methacrylate-based fluoropolymers to generate fluorous surfaces. Fluorous-tagged small molecules [perfluoroalkyl (Rf) amines] were immobilized on the fluorous surfaces via fluorous-fluorous interactions, thereby introducing reactive functional groups (amino moieties) on the surface. The amino groups displayed on the surface (accessible by a reactant) were successfully quantified using a reactive fluorophore, which enabled quantitative analysis of the Rf-amines immobilized on the fluorous surface that were available for the subsequent reaction. The effects of the molecular structures of the fluoropolymers and Rf-amines on the surface immobilization of Rf-amines were also investigated quantitatively. The surface coated with a fluoropolymer containing -C8F17 most effectively immobilized an Rf-amine comprising two -C6F13 chains. The adhered Rf-amines were easily removed by washing the surface with methanol, and then, they could successfully be reimmobilized on the surface. Finally, the presented approach enabled the rewritable micropatterning of an Rf-tagged biomolecule on a plastic surface through microcontact printing.

    AMER CHEMICAL SOC, 2022年01月, ACS APPLIED MATERIALS & INTERFACES, 14 (2), 3255 - 3263, 英語

    研究論文(学術雑誌)

  • Masao Nakayama, Hiroaki Akasaka, Eiichi Miyazaki, Yoshihiro Goto, Yuya Oki, Yosuke Kawate, Kenta Morita, Ryohei Sasaki

    Metal-based nanoparticles (NPs) have been extensively studied for dose enhancement applications in radiation therapy. This study investigated the utility of such NPs for image-guided radiation therapy (IGRT). Phantom images of gold NPs (AuNPs) and titanium peroxide NPs (TiOxNPs) with different concentrations were acquired using IGRT modalities, including cone-beam computed tomography (CBCT). AuNPs induced strong contrast enhancement in kV energy CBCT images, whereas TiOxNPs at high concentrations showed weak but detectable changes. The results indicated that these NPs can be used to enhance IGRT images as well as dose enhancement for treatment purposes.

    ELSEVIER, 2021年10月, PHYSICS & IMAGING IN RADIATION ONCOLOGY, 20, 94 - 97, 英語

    研究論文(学術雑誌)

  • Mimari Matsumoto, Kazuki Kaneko, Manami Hara, Masaki Matsui, Kenta Morita, Tatsuo Maruyama

    We propose a novel approach to stably immobilize gold nanoparticles (AuNPs) on a plastic substrate and demonstrate that the modified substrate is also capable of immobilizing biomolecules. To immobilize citrate-capped AuNPs, an acrylic substrate was simply dip-coated in a functional polymer solution to decorate the outermost surface with amino groups. Electrostatic interactions between AuNPs and the amino groups immobilized the AuNPs with a high density. The AuNP-modified acrylic substrate was transparent with a red tint. A heat treatment promoted the formation of amide bonds between carboxy groups on the AuNPs and amino groups on the substrate surface. These covalent bonds stabilized the immobilized AuNPs and the resulting substrate was resistant to washing with acid and thiol-containing solutions. The surface density of AuNPs was controlled by the surface density of amino groups on the substrate surface, which was in turn controlled by the dip-coating in the functional polymer solution. We attempted to immobilize functional biomolecules on the AuNPs-functionalized plastic surface by two different approaches. An enzyme (horseradish peroxidase) was successfully immobilized on the AuNPs through amide formation and 5 '-thiolated DNA was also immobilized on the AuNPs through S-Au interactions. These chemistries allow for simultaneous immobilization of two different kinds of biomolecules on a plastic substrate without loss of their functional properties.

    ROYAL SOC CHEMISTRY, 2021年07月, RSC ADVANCES, 11 (38), 23409 - 23417, 英語

    研究論文(学術雑誌)

MISC

  • Kenta Morita, Takahiro Suzuki, Yuya Nishimura, Kazuhisa Matsumoto, Chiya Numako, Kazuyoshi Sato, Masao Nakayama, Ryohei Sasaki, Chiaki Ogino, Akihiko Kondo

    Polyacrylic acid (PAA)-modified titanium peroxide nanoparticles (PAA-TiOx NPs) are promising radiosensitizers. PAA-TiOx NPs were synthesized from commercial TiO2 nanoparticles that were modified with PAA and functionalized by H2O2 treatment. To realize practical clinical uses for PAA-TiOx NPs, their tissue distribution and acute toxicity were evaluated using healthy mice and mice bearing tumors derived from xenografted MIAPaCa-2 human pancreatic cancer cells. Healthy mice were injected with PAA-TiOx NPs at 25 mg/kg body weight via the tail vein, and tumor-bearing mice were injected either into the tumor locally or via the tail vein. The concentration of PAA-TiOx NPs in major organs was determined over time using inductively coupled plasma atomic emission spectrometry. After 1 h, 12% of the PAA-TiOx NP dose had accumulated in the tumor, and 2.8% of the dose remained after 1 week. Such high accumulation could be associated with enhanced permeability and retention effects of the tumor, as PAA-TiOx NPs are composed of inorganic particles and polymers, without tumor-targeting molecules. The liver accumulated the largest proportion of the injected nanoparticles, up to 42% in tumor-bearing mice. Blood biochemical parameters were also investigated after intravenous injection of PAA-TiOx NPs in healthy mice. PAA-TiOx NPs invoked a slight change in various liver-related biochemical parameters, but no liver injury was observed over the practical dose range. In the future, PAA-TiOx NPs should be modified to prevent accumulation in the liver and minimize risk to patients. (C) 2018, The Society for Biotechnology, Japan. All rights reserved.

    SOC BIOSCIENCE BIOENGINEERING JAPAN, 2018年07月, JOURNAL OF BIOSCIENCE AND BIOENGINEERING, 126 (1), 119 - 125, 英語, 国内誌

  • 3P-225 ナノ粒子とX線照射を併用した深部ガンの非侵襲的治療法の開発(生体医用工学,人工臓器,一般講演)

    田野 亜都里, 森田 健太, 荻野 千秋, 佐藤 和好, 沼子 千弥, 中山 雅央, 佐々木 良平, 近藤 昭彦

    日本生物工学会, 2013年, 日本生物工学会大会講演要旨集, 65, 244 - 244, 日本語

  • 無機とバイオの融合ナノ粒子による新しいがん治療戦略 (特集 豊かな未来社会を築く粉体技術)

    西村 勇哉, 森田 健太, 鈴木 貴弘, 荻野 千秋, 近藤 昭彦

    ホソカワミクロン, 2017年, 粉砕 = The micromeritics, (60), 13 - 19, 日本語

所属学協会

  • 日本生物工学会

    2022年01月 - 現在
  • 高分子学会

    2020年06月 - 現在
  • 日本化学工学会

    2017年04月 - 現在
  • 日本DDS学会

    2018年07月 - 2019年08月
  • 日本生物工学会学生会員

    2014年06月 - 2017年03月

共同研究・競争的資金等の研究課題

  • 異種分子の自己組織化に基づく薬理機能制御が可能なメディカルゲル

    森田 健太

    日本学術振興会, 科学研究費助成事業 研究活動スタート支援, 研究活動スタート支援, 神戸大学, 2020年09月11日 - 2022年03月31日

    本研究は、低分子ゲル化剤の自己組織化現象を積極的に利用することで既存薬の薬理活性を制御することを目的としている。低分子ゲルは、そのゲル内に疎水空間と親水空間およびその界面を有しており、種々の機能をプログラム可能な合成分子でもある。この性質を利用し、認可済み薬剤と低分子ゲルを組み合わせることで、その薬効・対象菌種・持続性を人工的に制御可能であることを実証しようと試みた。 これまでにAc-FFFGKという配列のペプチドゲル化剤(P1)は生体適合性が高いという知見が得られていたため、低分子ゲル化剤のモデルとしてまずはこれを用いた。疎水性薬剤のモデルとしては、古くから利用される抗真菌薬であるAmphotericin B(AmB)を選択した。P1をAmBと共に純水に投入し加熱するだけでAmBは水に可溶化され、室温で冷却すると直ちにゲル化した。こうして作製されたAmB-P1ゲルは高濃度のAmBを含有していることから、当然真菌に対して抗菌活性を有するものと予想された。しかし、実際には、AmBが抗菌活性を発揮する最低濃度の100倍のAmBを含むAmB-P1ゲルに真菌を播種しても真菌は全く問題なく生育した。すなわち、P1はAmBをその自己組織化体にco-assemblyすることでAmBを水溶化できるが、AmB自体の毒性はマスクしてしまうということを発見した。また、P1がゲル化濃度以下でAmBと共存する場合はP1-AmBミセルを形成してAmBを可溶化することも見出した。その際、P1-AmBゲルと同様にP1-AmBミセルの抗菌活性はAmB単体より弱化されていた。さらに、P1-AmBミセルにキモトリプシンを加えてP1を分解し、AmBの毒性を回復させることに成功した。当初の予定とは異なるが、低分子ゲル化剤の自己組織化を利用した薬剤の機能制御に成功したといえる。以上の結果を論文化し投稿準備中である。

  • 中山 雅央, 江島 泰生, 吉田 賢史, 赤坂 浩亮, 森田 健太

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2016年04月01日 - 2019年03月31日

    これまでの研究で過酸化チタンナノ粒子はX線照射により活性酸素種を生成することがわかっていたが、本研究ではX線照射の有無に関わらずこのナノ粒子自身から過酸化水素が除放されていることを明らかにした。同じくX線照射により活性酸素種を生成するが過酸化水素は生成しない金ナノ粒子と比較したところ、その抗腫瘍効果は過酸化チタンナノ粒子の方が優れており、過酸化水素が放射線増感効果に大きく寄与していることが示唆された。一方で、静脈投与では約1割のナノ粒子しか腫瘍に集積しておらず、その多くが肝臓に集積していることが判明し、効率的な投与方法の検討が今後の課題となった。

  • 病原性アミロイドの破壊的自己組織化を誘発する両親媒性オリゴペプチドの設計

    森田 健太

    日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2021年04月01日 - 2023年03月31日