Theranostic Development for myocarditis.

• Project/Area Number: 17K19659
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine and related fields
• Research Institution: Osaka University
• Principal Investigator: Matsuzaki Takashi 大阪大学, 医学系研究科, 特任講師(常勤) (90456939)
• Co-Investigator(Kenkyū-buntansha): 富 海英 大阪大学, 医学系研究科, 特任助教(常勤) (70754646) ; 相楽 郁恵 大阪大学, 医学系研究科, 特任研究員 (40808474)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 心筋炎 / DDS / 診断と治療 / nAChR選択的アゴニスト / Gd / リポソーム / 劇症型心筋炎 / ガドリニウム / 循環器内科学 / ナノリポソーム / drug delivery system

Outline of Final Research Achievements

In this study, using the nano-liposome-based platform DDS technology, we addressed the theranostic development for fatal myocarditis, where there are still unmet needs for specific diagnosis and effective treatment. First, we optimized the formulation and the production conditions for Gd-labeled liposome by microfluidic technique. The Gd liposome showed elevated blood retention and efficient delivery of Gd to the myocardial heart. These results suggest that Gd liposome may be valuable for early diagnosis of myocarditis with magnetic resonance imaging.
Second, we optimized the formulation and the production conditions for alpha7 nAChR agonist encapsulated liposome with microfluidic technique. The agonist liposome reveled significant increase in the level of agonist in myocardial heart and ameliorated cardiac functions in rat autoimmune myocarditis model. These results suggest that the agonist liposome may be a promising therapeutic strategy for the treatment of myocarditis.

Academic Significance and Societal Importance of the Research Achievements

本研究は、有効な診断・治療法がなく致死率が極めて高い劇症型心筋炎に対し、ナノリポソームをプラットフォームとしたDDS技術を用い、診断と治療を一体化して開発するもので、劇症型心筋炎のアンメットメディカルニーズの解決に挑戦する高い社会的意義を有する。また、ナノリポソームDDSを診断法と治療法の共通プラットフォーム技術として利用することで、これまでの医療において別々の概念であった診断と治療が融合した全く新しい医療概念「Theragnosis（therapy + diagnosis）」を確立し、安心・安全な医療サービスを社会に提供することに貢献する。

Research Products

• [Journal Article] Anti-HB-EGF Antibody-Mediated Delivery of siRNA to Atherosclerotic Lesions in Mice (2018)
  • Author(s): Shota Tsuchida, Takashi Matsuzaki, Masaki Yamato, Keiji Okuda, Hai Ying Fu, Ryo Araki, Shoji Sanada, Hiroshi Asanuma, Yoshihiro Asano, Masanori Asakura, Hiroyuki Hao, Seiji Takashima, Masafumi Kitakaze, Yasushi Sakata, Eisuke Mekada, Tetsuo Minamino
  • Journal Title: International Heart Journal Volume: 59 Issue: 6 Pages: 1425-1431
  • DOI: 10.1536/ihj.17-644
  • NAID: 130007522227
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2018-11-30
  • Peer Reviewed