Development of an antioxidative nano-particle for redox sensoring and reno-protection

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tsukuba University of Technology
• Principal Investigator: HIRAYAMA Aki 筑波技術大学, 保健科学部, 教授 (20323298)
• Co-Investigator(Kenkyū-buntansha): NAGASAKI Yukio 筑波大学, 数理物質科学研究科, 教授 (90198309)
• Project Period (FY): 2009 – 2011
• Keywords: 急性腎障害 / ナノ粒子 / 酸化ストレス / ドラッグデリバリーシステム / 腎保護薬 / 電子スピン共鳴

Research Abstract

A TEMPO radical containing nano-particle (RNP) which possessed high in vivo stability and antioxidative effects was synthesized and applied to a treatment of acute kidney injury (AKI) model. RNP was synthesized as a micelle containing TEMPO in the core and poly(ethelenglycol)-poly(chloromethylstyrene) as its outer shell (PEG-PCTEMPO). Controlling the amino group of the repeating units of PCTEMPO, we synthesized pH-sensitive RNP (N-RNP) which release the inner TEMPO in acidic circumstance. RNP showed significant reno-protection through its high in vivo stability and target-specificity against tissue with high oxidative stress.

Research Products

• [Journal Article] The ROS scavenging and renalprotective effects of pH-responsive nitroxide radical containingnanoparticles. (2011)
  • Author(s): Yoshitomi T, Hirayama A, Nagasaki Y.
  • Journal Title: Biomaterials Volume: 32(31) Pages: 8021-8
  • DOI: DOI:10.1016/j.biomaterials.2011.07.014
• [Journal Article] Newly synthesized radical-containingnanoparticles (rnp) enhance neuro protection after cerebral ischemia reperfusion injury (2011)
  • Author(s): Marushima A, Suzuki K, Nagasaki Y, Yoshitomi T, Tou K, Tsurushima H, Hirayama A, Matsumura A.
  • Journal Title: Neurosurgery Volume: 68(5) Pages: 1418-26
  • DOI: DOI:10.1227/NEU.0b013e31820c02d9
• [Journal Article] Spherical carbon adsorbent (AST-120) protects deterioration of renal function in chronic kidney disease rats through inhibition of reactive oxygen species production from mitochondria and reduction of serum lipid peroxidation (2010)
  • Author(s): Owada S, Maeba T, Sugano Y, Hirayama A, Ueda A, Nagase S, Goto S, Nishijima F, Bannai K, Yamato H
  • Journal Title: Nephron Exp Nephrol Volume: 115(4)
• [Journal Article] pH-Sensitive Radical.Containing-Nanoparticle (RNP) for theL-Band-EPR Imaging of Low pH Circumstances (2009)
  • Author(s): Yoshitomi T, Suzuki R, Mamiya T, Matsui H, Hirayama A, Nagasaki Y.
  • Journal Title: Bioconjugate Chem Volume: 20 Pages: 1792-1798
• [Presentation] レドックス反応性ナノ粒子による腎虚血再灌流障害の治療第 (2011)
  • Author(s): 吉冨徹,平山暁,長崎幸夫
  • Organizer: 64回日本酸化ストレス学会学術集会
  • Place of Presentation: 北海道,ルスツ
  • Year and Date: 20110700
• [Presentation] 急性腎障害に対するナノ粒子治療の開発シンポジウムJapan Kidney Week 2011 (2011)
  • Author(s): 平山暁,吉富徹,長崎幸夫
  • Organizer: 第55回(社)日本透析医学会学術集会・総会
  • Place of Presentation: 横浜
  • Year and Date: 20110600
• [Presentation] Novel redox nanotherapy fof renal ischemia reperfusion injury (2011)
  • Author(s): Nagasaki Y, Yoshitomi T, Hirayama A
  • Organizer: XLVIII ERA-EDTA Congress
  • Place of Presentation: Prague, Czech Rep
  • Year and Date: 20110600
• [Presentation] Application of ESR and Spin Technologies for the Control of Kidney Diseases (2011)
  • Author(s): Hirayama A, Ueda A, Nagase S, Aoyagi K, Owada S
  • Organizer: International Workshop"Advanced ESR Studies for New Frontiers in Biofunctional Spin Science and Technology"(AEBST 2011)
  • Place of Presentation: Kobe
  • Year and Date: 2011-11-13
• [Presentation] Development of a pH-Sensitive Reno-Protective Nano-Particle for Relief of Ischemia-Reperfusion Acute Kidney Injury (2010)
  • Author(s): Hirayama A, Yoshitomi T, Owada S, Ueda A, Matsui H, Aoyagi K, Nagasaki Y
  • Organizer: 43rd Annual meeting of the American Society of Nephrology (Renal Week 2010)
  • Place of Presentation: Denver (abstract in J Am Soc Nephrol)
  • Year and Date: 20101118-21
• [Presentation] Design of redox imaging nanoprobe using nitroxyl radical containing nanoparticle (2010)
  • Author(s): Yoshitomi T, Mamiya T, Matsui H, Hirayama A ,Nagasaki Y
  • Organizer: SFRBM 2010-17th Annual Meeting of the Society for Free Radical Biology and Medicine
  • Place of Presentation: Orlando, Florida
  • Year and Date: 20101117-21
• [Presentation] Design of nitroxyl radicals containing nanoparticle for MR imaging of tumor (2010)
  • Author(s): Yoshitomi T, Matsumoto S, Krishna MC, Matsumoto K, Anzai K, Matsui H, Hirayama A, Nagasaki Y
  • Organizer: The 37th Annual Meeting and Exposition of the Controlled Release Society
  • Place of Presentation: Oregon Convention Center, Portland, Oregon, USA.
  • Year and Date: 20100710-14
• [Presentation] 反応性イメージングを目指したニトロキシルラジカル含有ナノ粒子の設計と評価 (2010)
  • Author(s): 吉冨徹、間宮孝、松井裕史、平山暁、長崎幸夫
  • Organizer: 第26回日本DDS学会学術集会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 20100617-18
• [Presentation] Design of pH-sensitive polymeric micelle possessing reduced forms of TEMPO for imaging of ROS (2010)
  • Author(s): Yoshitomi T, Mamiya T, Matsui H, Hirayama A, Nagasaki Y
  • Organizer: Young Investigator's Award winning presentation
  • Place of Presentation: Oxygen Club California World Congress, Santa Barbara, CA, USA.
  • Year and Date: 20100317-20
• [Presentation] Development of TEMPOL-Containing Nano-Particle for Continuous Superoxide Scavenging and Antihypertension. (2009)
  • Author(s): Hirayama A, Yoshitomi T, Ueda A, Matsui H, Owada S, Aoyagi K, Nagasaki Y
  • Organizer: 42nd Annual meeting of the American Society of Nephrology (Renal Week 2009)
  • Place of Presentation: San Diego
  • Year and Date: 20091100
• [Presentation] Healing of Oxidative Stress in Brain on the Occasion of Cerebral Ischemia-Reperfusion. (2009)
  • Author(s): Yoshitomi T, Toh K, Marushima A, Suzuki K, Tsurushima H, Hirayama A, Matsumura A, Nagasaki Y
  • Organizer: 2009 Gordon Research Conference on Biomaterials: Biocompatibility and Tissue Engineering
  • Place of Presentation: Plymouth (USA)
  • Year and Date: 20090717-24
• [Presentation] ラジカル含有ナノ粒子を用いた脳虚血-再潅流モデルラットにおける脳梗塞の抑制 (2009)
  • Author(s): 藤加珠子、吉冨徹、丸島愛樹、鈴木謙介、鶴嶋英夫、平山暁、松村明、長崎幸夫
  • Organizer: 第62回日本酸化ストレス学会学術集会
  • Place of Presentation: 福岡ポスターアワード(優秀演題賞)受賞演題)
  • Year and Date: 20090611-12
• [Presentation] TEMPO含有ナノ粒子の開発と生体内動態 (2009)
  • Author(s): 吉冨徹、平山暁、間宮孝、松井裕史、長崎幸夫
  • Organizer: 第48回電子スピンサイエンス学会年会(SEST2009)
  • Place of Presentation: 神戸
  • Year and Date: 2009-11-12
• [Presentation] 生体内ROSの可視化を目指したEPRナノプローブの創製 (2009)
  • Author(s): 吉冨徹、間宮孝、松井裕史、平山暁、長崎幸夫
  • Organizer: 第62回日本酸化ストレス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-06-11
• [Presentation] 安定した抗酸化・降圧効果を発揮するナノ粒子化TEMPOの開発 (2009)
  • Author(s): 平山暁,吉冨徹,植田敦志,青柳一正,長崎幸夫
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-03
• [Patent(Industrial Property Rights)] 高分子環状ニトロキシドラジカル化合物とシリカの有機.無機ハイブリッド複合体 (2012)
  • Inventor(s): 長崎幸夫,吉冨徹,池田豊,植田敦志,平山暁,矢口達也,山下真代
  • Industrial Property Rights Holder: 国立大学法人筑波大学,国立大学法人筑波技術大学
  • Industrial Property Number: 特許、特願2012-024460
  • Filing Date: 2012-02-07
• [Patent(Industrial Property Rights)] Polymerized cyclic nitroxide radical compound, and use thereof (2009)
  • Inventor(s): NAGASAKI Yukio, YOSHITOMI Toru, MATSUI Hirofumi, HIRAYAMA Aki,MAMIYA Takashi, MATSUMURA Akira, SUZUKI Kensuke, TSURUSHIMA Hideo,MARUSHIMA Aiki, TOH Kazuko, MIYAMOTO Daisuke
  • Industrial Property Rights Holder: NAGASAKI Yukio, YOSHITOMI Toru, MATSUI Hirofumi, HIRAYAMA Aki, MAMIYA Takashi, MATSUMURA Akira, SUZUKI Kensuke, TSURUSHIMA Hideo, MARUSHIMA Aiki, TOH Kazuko, MIYAMOTO Daisuke, University of Tsukuba
  • Industrial Property Number: 特許(PCT出願)、WO/2009/133647, PCT/JP2008/072467
  • Filing Date: 2009-05-11
  • Overseas