Targeted heart hyperthermia for heart failure using gold nano-rod

• Project/Area Number: 24591098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyushu University
• Principal Investigator: HIGUCHI Yoshihiro 九州大学, 大学病院, 助教 (40404032)
• Co-Investigator(Kenkyū-buntansha): KOYANAGI Masamichi 九州大学病院別府病院, 内科, 助教 (00325474) ; MAEDA Toyoki 九州大学病院別府病院, 内科, 准教授 (30264112) ; MAKINO Naoki 九州大学病院別府病院, 内科, 名誉教授 (60157170) ; 新留 琢郎 熊本大学, 自然科学研究科, 教授 (20264210)
• Co-Investigator(Renkei-kenkyūsha): NIIDOME Takuro 熊本大学, 自然科学研究科, 教授 (20264210)
• Research Collaborator: TSUCHIDA Keiko
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 金ナノロッド / 心不全 / 温熱療法 / 循環器 / ナノテクノロジー / トランスジェニックマウス / サイトカイン / 心臓局所温熱 / 近赤外線レーザー

Outline of Final Research Achievements

Gold nanorods (GNRs), rod-shaped gold nanoparticles, act as both contrast agents for in vivo bioimaging and thermal converters for photothermal therapy to treat inflammatory disorders. Pro-inflammatory cytokines play critical roles in the development of heart failure. We herein examined the delivery of GNRs into the inflammatory heart in a transgenic mouse (TG) model of inflammatory cardiomyopathy with the cardiac specific overexpression of TNF-α. We modified GNRs with polyethylene glycol (PEGylated GNRs) to avoid cytotoxicity and reduce the rapid clearance of nanoparticles from the blood. PEGylated GNRs were administered intravenously in TG and wild-type mice. A quantitative analysis of Au was performed using inductively coupled plasma mass spectrometry (ICP-MS). Approximately twice more Au was detected in the TG heart. We herein demonstrated that PEGylated GNRs are prone to accumulate in the heart with inflammatory cardiomyopathy.

Research Products

• [Journal Article] Upregulation of anticoagulant proteins, protein S and tissue factor pathway inhibitor, in the mouse myocardium with cardio-specific TNF-alpha overexpression (2012)
  • Author(s): Higuchi Y, Kubota T, Koyanagi M, Maeda T, Feldman AM, Makino N.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 302(11) Issue: 11 Pages: H2352-H2362
  • DOI: 10.1152/ajpheart.01026.2011
  • Peer Reviewed
• [Presentation] Accumulation of gold nanorods in the failing heart of Transgenic Mice with a Cardiac-Specific TNF-α Expression (2015)
  • Author(s): 樋口 義洋
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-04-26
• [Presentation] Thrombomodulin Alpha Improved the Cardiac Function but not Hypertrophy in a Transgenic Mouse Model of Inflammatory Cardiomyopathy (2013)
  • Author(s): Higuchi Y, Koyanagi M, Kubota T, Feldman AM, and Makino N.
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: パシフィコ横浜
• [Presentation] A Selective Inhibitor of c-Fos/Activator Protein-1 Inhibits IL-1β; Production and Improves Heart Failure in Transgenic Mice with Cardiac-Specific TNF-α Expression
  • Author(s): 樋口 義洋
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム