Development of novel hybrid anti-oxidant based on albumin fusion technology and its therapeutic application on acute radiation syndrome

• Project/Area Number: 15K15008
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Sojo University
• Principal Investigator: OTAGIRI Masaki 崇城大学, 薬学部, 教授 (80120145)
• Co-Investigator(Kenkyū-buntansha): 異島 優 徳島大学, 薬学部, 准教授 (00457590) ; 田口 和明 崇城大学, 薬学部, 助教 (90621912)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 組織指向性機能性アルブミン / 包括的放射線防護療法 / ハイブリッド型抗酸化アルブミン / 体内動態特性 / 機能性アルブミン / 抗酸化アルブミン / リポソーム

Outline of Final Research Achievements

We have been constructed a albumin fusion technology that is albe to create albumin dervaties with multiple functions. In the present study, we attmpted to develop a novel anti-oxidant that combined both blood retention property and cell penetrating activity based on albumin fusion technology. This hybrid type of aniti-oxidant exhibited superior radical scavenging activity both in vitro and in vivo. In addition, this anti-oxidant showed similar blood retention property comparable to wild type albumin. Poly-sulfared glutathiones that released from hybrid albumin efficiently transfered into the cells. Moreover, hybrid albumin inhibited radiation injury effectively and hence, significantly recovered the survibal rate against model mice of acute radiation syndrome via anti-oxidative and anti-inflammatory action. Thus, a hybrid type of anti-oxidant albumin that developed in this study has a potential as a novel therapeutics aganst acute radiation syndrome.

Research Products

• [Int'l Joint Research] CurtinUniversity(オーストラリア)
• [Journal Article] Oral branched-chain amino acid granules improve structure and function of human serum albumin in liver cirrhotic patients (2017)
  • Author(s): Setoyama H, Tanaka M, Nagumo K, Naoe H, Watanabe T, Yoshimaru Y, Tateyama M, Sasaki M, Watanabe H, Otagiri M, Maruyama T and Sasaki Y
  • Journal Title: J Gastroenterol Volume: - Issue: 6 Pages: 754-765
  • DOI: 10.1007/s00535-016-1281-2
  • Peer Reviewed / Open Access
• [Journal Article] The Binding of Silibinin, the Main Constituent of Silymarin, to Site I on Human Serum Albumin (2017)
  • Author(s): Yamasaki K, Sato H, Minagoshi S, Kyubun K, Anraku M, Miyamura S, Watanabe H, Taguchi K, Seo H, Maruyama T, Otagiri M
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 40 Issue: 3 Pages: 310-317
  • DOI: 10.1248/bpb.b16-00790
  • NAID: 130005398492
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Quantitative determination of polysulfide in albumins, plasma proteins and biological fluid samples using a novel combined assays approach (2017)
  • Author(s): keda, M. Ishima, Y. Shibata, A. Chuang, V. T. G. Sawa, T. Ihara, H. Watanabe, H. Xian, M. Ouchi, Y. Shimizu, T. Ando, H. Ukawa, M. Ishida, T. Akaike, T. Otagiri, M. Maruyama, T.
  • Journal Title: Analytica Chimica Acta Volume: 969 Pages: 18-25
  • DOI: 10.1016/j.aca.2017.03.027
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of the Pharmacokinetic Properties of Hemoglobin-Based Oxygen Carriers. (2017)
  • Author(s): Taguchi K, Yamasaki K, Maruyama T, Otagiri M.
  • Journal Title: J Funct Biomater. Volume: 8 Issue: 1 Pages: 0-0
  • DOI: 10.3390/jfb8010011
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Implications Associated With the Posttranslational Modification-Induced Functional Impairment of Albumin in Oxidative Stress-Related Diseases. (2017)
  • Author(s): Watanabe H, Imafuku T, Otagiri M, Maruyama T.
  • Journal Title: J Pharm Sci. Volume: S0022-3549 Issue: 9 Pages: 18-25
  • DOI: 10.1016/j.xphs.2017.03.002
  • Peer Reviewed
• [Journal Article] N-acetyl-L-methionine is a superior protectant of human serum albumin against post-translational oxidation as compared to N-acetyl- L-tryptophan (2016)
  • Author(s): Kouno Y, Anraku M, Yamasaki K, Okayama Y, Iohara D, Nakamura H, Maruyama T, Hirayama F, Kragh-Hansen U, Otagiri M.
  • Journal Title: Biochemistry and BiophysicsReports Volume: 6 Pages: 266-274
  • DOI: 10.1016/j.bbrep.2016.04.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Human serum albumin hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease (2016)
  • Author(s): Shibata A, Ishima Y, Ikeda M, Sato H, Imafuku T, Chuang VT, Ouchi Y, Abe T, Watanabe H, Ishida T, Otagiri M, Maruyama T
  • Journal Title: Biochem Biophys Res Commun Volume: 479 Issue: 3 Pages: 578-583
  • DOI: 10.1016/j.bbrc.2016.09.113
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Carbon monoxide-bound hemoglobin vesicles ameliorate multiorgan injuries induced by severe acute pancreatitis in mice by their anti-inflammatory and antioxidant properties. (2016)
  • Author(s): Nagao S, Taguchi K, Sakai H, Yamasaki K, Watanabe H, Otagiri M, Maruyama T
  • Journal Title: Int J Nanomedicine. Volume: 11 Pages: 5611-5620
  • DOI: 10.2147/ijn.s118185
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mutants and molecular dockings reveal that the primary L-thyroxine binding site in human serum albumin is not the one which can cause familial dysalbuminemic hyperthyroxinemia. (2016)
  • Author(s): Kragh-Hansen U, Minchiotti L, Coletta A, Bienk K, Galliano M, Schiott B, Iwao Y, Ishima Y, Otagiri M
  • Journal Title: Biochim Biophys Acta. Volume: 1860 Issue: 4 Pages: 648-660
  • DOI: 10.1016/j.bbagen.2016.01.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Olmesartan protects endothelial cells against oxidative stress-mediated cellular injury. (2015)
  • Author(s): Kadowaki D, Anraku M, Sakaya M, Hirata S, Maruyama T, Otagiri M.
  • Journal Title: Clin Exp Nephrol. Volume: 19 Issue: 6 Pages: 1007-1014
  • DOI: 10.1007/s10157-015-1111-5
  • Peer Reviewed / Open Access
• [Journal Article] Amino acids of importance for the antioxidant activity of human serum albumin as revealed by recombinant mutants and genetic variants. (2015)
  • Author(s): Anraku M, Shintomo R, Taguchi K, Kragh-Hansen U, Kai T, Maruyama T, Otagiri M.
  • Journal Title: Life Sci. Volume: 134 Pages: 36-41
  • DOI: 10.1016/j.lfs.2015.05.010
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute. (2015)
  • Author(s): Haruki R, Kimura T, Iwasaki H, Yamada K, Kamiyama I, Kohno M, Taguchi K, Nagao S, Maruyama T, Otagiri M, Komatsu T.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 12778-12778
  • DOI: 10.1038/srep12778
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury. (2015)
  • Author(s): Nishida K, Watanabe H, Ogaki S, Kodama A, Tanaka R, Imafuku T, Ishima Y, Giam Chuang VT, Toyoda M, Kondoh M, Wu Q, Fukagawa M, Otagiri M, Maruyama T.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 14471-14471
  • DOI: 10.1038/srep14471
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Therapeutic application of bone marrow-targeted liposome ～Encapsulation of erythropoietin for renal anemia treatment～ (2017)
  • Author(s): Kazuaki Taguchi, Toru Maruyama, Keitaro Sou, Masaki Otagiri
  • Organizer: International Symposium on Drug Delivery and Pharmaceutical Sciences: Beyond the History (ISDDPS)
  • Place of Presentation: Kyoto Reserch Park（京都府・京都市)
  • Year and Date: 2017-03-09
  • Int'l Joint Research
• [Presentation] クラッシュ症候群モデルラットに対する一酸化炭素付加赤血球の有用性評価 (2016)
  • Author(s): 丸山徹、大柿滋、永崎太清、柳澤 洋輝、永尾 紗理、田口 和明、渡邊 博志、小田切 優樹
  • Organizer: 第23回日本血液代替物学会年次大会
  • Place of Presentation: 早稲田大学西早稲田キャンパス（東京都・新宿区）
  • Year and Date: 2016-11-24
• [Presentation] NASH病態におけるDDS戦略の限界と一酸化窒素による治療抵抗性の克服 (2016)
  • Author(s): 前田 仁志、異島 優、皆吉 勇紀、一水 翔太、柳澤 洋輝、 渡邊 博志、小田切 優樹、丸山 徹
  • Organizer: 第38回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 名古屋市立大学大学院薬学研究科・薬学部（愛知県・名古屋市）
  • Year and Date: 2016-11-17
• [Presentation] 新規酸化ストレス早期発見に向けた血清パースルフィド定量の有用性評価 (2016)
  • Author(s): 池田真由美、異島 優、渡邊博志、石田竜弘、小田切優樹、丸山 徹
  • Organizer: 第38回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 名古屋市立大学大学院薬学研究科・薬学部（愛知県・名古屋市）
  • Year and Date: 2016-11-17
• [Presentation] Albumin as Nitric Oxide-Traffic Protein : Novel Anticancer Agent (2016)
  • Author(s): Masaki Otagiri, Yu Ishima, Toru Maruyama
  • Organizer: International Conference On Nanomedicine And Nanobiotechnology 2016
  • Place of Presentation: Paris（France)
  • Year and Date: 2016-09-28
  • Int'l Joint Research
• [Presentation] バイオミメティックな一酸化炭素デリバリーによる炎症性腸疾患の治療効果 (2016)
  • Author(s): 永尾 紗理、田口 和明、酒井 宏水、小田切 優樹、丸山 徹
  • Organizer: 第32回日本DDS学会学術集会
  • Place of Presentation: グランシップ 静岡コンベションアーツセンター（静岡県・静岡市）
  • Year and Date: 2016-06-30
• [Presentation] 組換え型高マンノース付加アルブミンを担体とした肝クッパー細胞指向性インターフェロンα2bの設計と肝保護効果 (2016)
  • Author(s): 皆吉 勇紀、前田 仁志、渡邊 博志、異島 優、小田切 優樹、丸山 徹
  • Organizer: 第32回日本DDS学会学術集会
  • Place of Presentation: グランシップ 静岡コンベションアーツセンター（静岡県・静岡市）
  • Year and Date: 2016-06-30
• [Presentation] Therapeutic Impact of Liver-Targeted Nitric Oxide Releasing Nano-Antioxidant on NASH (2016)
  • Author(s): Hitoshi Maeda, Yu Ishima, Yuki Minayoshi, Shouta Ichimizu, Hiroshi Watanabe, Masaki Otagiri, Toru Maruyama
  • Organizer: The 1st Workshop for Japan-Korea Young Scientists on Pharmaceutics
  • Place of Presentation: 京都教育文化センター（京都府・京都市）
  • Year and Date: 2016-06-24
  • Int'l Joint Research
• [Presentation] ヒト血清アルブミン－オクタン酸ナトリウム－N-アセチル-L-メチオニン三元複合体のX線結晶構造解析 (2016)
  • Author(s): 小田切優樹、河合聡人、河野陽介、安楽誠、山崎啓之
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 長良川国際会議場および岐阜都ホテル（岐阜県・岐阜市）
  • Year and Date: 2016-05-19
• [Presentation] アルブミンとリポソームを融合した新規 DDS キャリ アの創製 (2016)
  • Author(s): 岡本 侑子
  • Organizer: 日本薬学会 第136年会
  • Place of Presentation: パシィフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-26
• [Presentation] 抗がん剤封入ヒト血清アルブミンナノ粒子の設計 (2016)
  • Author(s): 木村 虎太郎
  • Organizer: 日本薬学会 第136年会
  • Place of Presentation: パシィフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-26
• [Presentation] N-acetyl-L-methionine is a superior protectant of human serum albumin against photo-oxidation and reactive oxygen species compared to N-acetyl-L-tryptophan (2015)
  • Author(s): Yousuke Kouno
  • Organizer: Asian Federation for Pharmaceutical Sciences (AFPS) Conference 2015
  • Place of Presentation: Rama Gardens Hotel (Bangkok,Thailand)
  • Year and Date: 2015-11-25
  • Int'l Joint Research
• [Presentation] 人工赤血球製剤ヘモグロビン小胞体の体内動態 (2015)
  • Author(s): 小田切優樹
  • Organizer: 臨床応用化を目指した人工赤血球関連セミナー
  • Place of Presentation: 旭川医科大学（北海道旭川市）
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] DESIGN AND EVALUATION OF RECOMBINANT ALBUMIN DOMAIN WITH HIGH BILIRUBIN BINDING AFFINITY VIA PHAGE DISPLAY TECHNOLOGY (2015)
  • Author(s): Masaki Otagiri
  • Organizer: International Bioanalytical Formulation Congress
  • Place of Presentation: Maritim proArte Hotel (Berlin,Germany)
  • Year and Date: 2015-09-15
• [Presentation] CLINICAL APPLICABITY OF THIOREDOXIN-ALBUMIN FUSION PROTEIN AGAINST OXIDATIVE STRESS RELATED DISEASES (2015)
  • Author(s): Masaki Otagiri
  • Organizer: 15th International Conference on Oxidative Stress Reduction, Redox Homeostasis and Antioxidants
  • Place of Presentation: Institut Pasteur (Paris,France)
  • Year and Date: 2015-06-22
  • Int'l Joint Research / Invited