In vivo imaging of inflammasome activation for clinical diagnosis

• Project/Area Number: 18K19929
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Kyushu University
• Principal Investigator: MURATA MASAHARU 九州大学, 先端医療イノベーションセンター, 特任教授 (30304744)
• Co-Investigator(Kenkyū-buntansha): 梅野 太輔 千葉大学, 大学院工学研究院, 教授 (00400812) ; 赤星 朋比古 九州大学, 医学研究院, 准教授 (20336019) ; 橋爪 誠 九州大学, 先端医療イノベーションセンター, 名誉教授 (90198664) ; 河野 喬仁 九州大学, 先端医療イノベーションセンター, 特任助教 (90526831)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: ナノ材料 / DDS / 分子イメージング / 診断システム / 炎症 / 画像診断 / ナノバイオメディスン / インフラマソーム / 診断

Outline of Final Research Achievements

We are developed novelnano-drug carrier modeled on the viral capsid. In this project, we designed and created a functionalized contrast agent that can react specifically with inflammasome and change the signal according to its activity. As its platform, we use protein-based bio-nanocapsules (small heat shock protein, HSP16.5) and incorporate the concepts of protein engineering and evolutionary engineering to respond to inflammasome more sensitively and quantitatively. Was newly designed. The obtained recombinant was a spherical structure with a diameter of 20 nm and responded to inflammasome in a concentration-dependent manner.

Academic Significance and Societal Importance of the Research Achievements

がん組織に炎症細胞が浸潤していることは、病理学的に古くから知られており、慢性炎症と発がんは密接に関わっていると考えられてきた。特に近年は炎症反応により活性化するシグナル経路が発がんに関与していることが解明されつつあり、炎症応答を制御することでがん化やその進展を制御できる可能性も見えてきた。また炎症性疾患には本研究の目標であるNASHをはじめ、機序、診断法、そして治療法が開発途上にあるものも多く、炎症シグナルの中核を成すインフラマソームの解明が喫緊の課題となっている。本研究で開発したインフラマソーム応答型ナノカプセルはその造影剤として機能することができる。

Research Products

• [Journal Article] Effect of Fetal Bovine Serum Concentration on Lysophosphatidylcholine-mediated Proliferation and Apoptosis of Human Aortic Smooth Muscle Cells (2020)
  • Author(s): Asai, D, Kawano, T, Murata, M, Nakashima, H, Toita, R, Kang, J.H
  • Journal Title: Journal of Oleo Science Volume: 69 Issue: 3 Pages: 255-260
  • DOI: 10.5650/jos.ess19268
  • NAID: 130007804109
  • ISSN: 1345-8957, 1347-3352
  • Peer Reviewed / Open Access
• [Journal Article] In vivo melanoma imaging based on dynamic nuclear polarization enhancement in melanin pigment of living mice using in vivo dynamic nuclear polarization magnetic resonance imaging (2019)
  • Author(s): Hyodo Fuminori、Naganuma Tatsuya、Eto Hinako、Murata Masaharu、Utsumi Hideo、Matsuo Masayuki
  • Journal Title: Free Radical Biology and Medicine Volume: 134 Pages: 99-105
  • DOI: 10.1016/j.freeradbiomed.2019.01.002
  • Peer Reviewed
• [Journal Article] Suppression of lysophosphatidylcholine-induced human aortic smooth muscle cell calcification by protein kinase A inhibition (2019)
  • Author(s): Riki Toita, Daisuke Asai, Kentaro Otani, Takahito Kawano, Masaharu Murata, Jeong-Hun Kang
  • Journal Title: Lipids Volume: 54 Issue: 8 Pages: 465-470
  • DOI: 10.1002/lipd.12178
  • Peer Reviewed
• [Journal Article] Advanced multispectral image-processing endoscopy system for visualizing two-dimensional hemoglobin saturation and relative hemoglobin concentration (2019)
  • Author(s): Chiba Toru、Obara Yoshimi、Murata Masaharu、Akahoshi Tomohiko
  • Journal Title: Endoscopy International Open Volume: 07 Issue: 11 Pages: E1442-E1447
  • DOI: 10.1055/a-0990-9189
  • Peer Reviewed
• [Journal Article] Phase Separation Multi-phase Flow Using an Aqueous Two-phase System of a Polyethylene Glycol/Dextran Mixed Solution (2018)
  • Author(s): Naoya IMANISHI, Tetsuo YAMASAKI, and Kazuhiko TSUKAGOSHI, Masaharu MURATA
  • Journal Title: Analytical Sciences Volume: 34 Issue: 8 Pages: 953-958
  • DOI: 10.2116/analsci.18P105
  • NAID: 130007432308
  • ISSN: 0910-6340, 1348-2246
  • Year and Date: 2018-08-10
  • Peer Reviewed
• [Journal Article] Ligand-Mediated Coating of Liposomes with Human Serum Albumin (2018)
  • Author(s): Sato Hikari、Nakhaei Elnaz、Kawano Takahito、Murata Masaharu、Kishimura Akihiro、Mori Takeshi、Katayama Yoshiki
  • Journal Title: Langmuir Volume: 34 Issue: 6 Pages: 2324-2331
  • DOI: 10.1021/acs.langmuir.7b04024
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Protein kinase A (PKA) inhibition reduces human aortic smooth muscle cell calcification stimulated by inflammatory response and inorganic phosphate (2018)
  • Author(s): Riki Toita, Kentaro Otani, Takahito Kawano, Satoshi Fujita, Masaharu Murata, Jeong-Hun Kang
  • Journal Title: Life Sciences Volume: 209 Pages: 466-471
  • DOI: 10.1016/j.lfs.2018.08.051
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ultrasensitive MRI detection of spontaneous pancreatic tumors with nanocage-based targeted contrast agent. (2018)
  • Author(s): Kawano T, Murata M, Kang JH, Piao JS, Narahara S, Hyodo F, Hamano N, Guo J, Oguri S, Ohuchida K, Hashizume M
  • Journal Title: Biomaterials Volume: 152 Pages: 37-46
  • DOI: 10.1016/j.biomaterials.2017.10.029
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Increased hepatic inflammation in a normal-weight mouse after long-term high-fat diet feeding (2017)
  • Author(s): Riki TOITA, Takahito KAWANO, Satoshi FUJITA, Masaharu MURATA, Jeong-Hun KANG
  • Journal Title: Journal of Toxicologic Pathology Volume: 31 Issue: 1 Pages: 43-47
  • DOI: 10.1293/tox.2017-0038
  • NAID: 130006318210
  • ISSN: 0914-9198, 1881-915X
  • Peer Reviewed / Open Access
• [Journal Article] Postmortem interval estimation using the animal model of postmortem gas volume changes. (2017)
  • Author(s): Iwamoto C, Ohuchida K, Okumura M, Usumoto Y, Kishimoto J, Murata M, Ikeda N, Hashizume M.
  • Journal Title: Legal Medicine Volume: - Pages: 66-70
  • DOI: 10.1016/j.legalmed.2017.12.010
  • Peer Reviewed / Open Access