Medical imaging of pancreatic tumors with nanocage-based targeted contrast agent

• Project/Area Number: 15K16333
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Kyushu University
• Principal Investigator: KAWANO Takahito 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): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: MRI / 造影剤 / DDS / 画像診断システム / ナノ材料 / 分子イメージング / ナノカプセル

Outline of Final Research Achievements

Contrast agents with greater specificity and sensitivity are required for the diagnosis of pancreatic cancers by magnetic resonance imaging (MRI). In this study, small heat shock protein 16.5 (Hsp16.5)-based nanocages conjugated to gadolinium(III)-chelated contrast agents and iRGD peptides (which target neuropilin-1 expressed on pancreatic cancer cells) were developed. MRI data showed that larger nanocages had higher T1 relaxivity than smaller nanocages. Molecular MRI with protein nanocages was enabled to detect neuropilin-1-positive cells and to produce strong signal enhancement of spontaneous pancreatic tumors in engineered mouse models. Novel iRGD-modified nanocages displayed potential as a specific and sensitive MRI contrast agent for the diagnosis of pancreatic tumors for clinical translation.

Research Products

• [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] 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] In vivo redox metabolic imaging of mitochondria assesses disease progression in non-alcoholic steatohepatitis (2017)
  • Author(s): Nakata R, Hyodo F, Murata M, Eto H, Nakaji T, Kawano T, Narahara S, Yasukawa K, Akahoshi T, Tomikawa M, Hashizume M
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 17170-17170
  • DOI: 10.1038/s41598-017-17447-2
  • Peer Reviewed / Open Access
• [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] Noninvasive mapping of the redox status of dimethylnitrosamine-induced hepatic fibrosis using in vivo dynamic nuclear polarization-magnetic resonance imaging (2016)
  • Author(s): Kawano T, Murata M, Hyodo F, Eto H, Kosem N, Nakata R, Hamano N, Piao JS, Narahara S, Akahoshi T, Hashizume M
  • Journal Title: Scientific Reports Volume: - Issue: 1 Pages: 32604-32604
  • DOI: 10.1038/srep32604
  • Peer Reviewed / Open Access
• [Journal Article] Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10-conjugated liposomes in obese mice (2016)
  • Author(s): iki Toita, Takahito Kawano, Masaharu Murata, Jeong-Hun Kang
  • Journal Title: Biomaterials Volume: 110 Pages: 81-88
  • DOI: 10.1016/j.biomaterials.2016.09.018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2) (2016)
  • Author(s): Asai, D., Murata, M., Toita, R., Kawano, T., Nakashima, H., and Kang, J.H.
  • Journal Title: Amino Acids Volume: 48 Issue: 12 Pages: 2875-2880
  • DOI: 10.1007/s00726-016-2345-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Förster Resonance Energy Transfer-Based Self-Assembled Nanoprobe for Rapid and Sensitive Detection of Postoperative Pancreatic Fistula (2016)
  • Author(s): Nobuhito Hamano, Masaharu Murata, Takahito Kawano, Jing Shu Piao, Sayoko Narahara, Ryosuke Nakata, Tomohiko Akahoshi, Tetsuo Ikeda, and Makoto Hashizume
  • Journal Title: ACS Applied Materials & Interfaces Volume: 8 Issue: 8 Pages: 5144-5123
  • DOI: 10.1021/acsami.5b11902
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Design and function of engineered protein nanocages as a drug delivery system for targeting pancreatic cancer cells via neuropilin-1 (2015)
  • Author(s): Masaharu Murata, Sayoko Narahara, Takahito Kawano, Nobuhito Hamano, Jing Shu Piao, Jeong-Hun Kang, Kenoki Ohuchida, Takashi Murakami, Makoto Hashizume
  • Journal Title: Molecular Pharmaceutics Volume: in press Issue: 5 Pages: 1422-1430
  • DOI: 10.1021/mp5007129
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Basic FGF-treated adipose tissue-derived mesenchymel stem cell infusion ameliorate liver cirrhosis via paracrine HGF (2015)
  • Author(s): Tang W, Aakahoshi T, Piao J, Narahara S, Murata M, Kawano T, Hamano N, Ikeda T, Hashizume M
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 20 Issue: 6 Pages: 1065-1074
  • DOI: 10.1111/jgh.12893
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Applications of human hepatitis B virus preS domain in bio-and nanotechnology (2015)
  • Author(s): R. Toita, T. Kawano, J.-H. Kang, M. Murata
  • Journal Title: World Journal of Gastroenterology Volume: 28 Issue: 24 Pages: 7400-7411
  • DOI: 10.3748/wjg.v21.i24.7400
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Monitoring of phosphorylated peptides by radioactive assay and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (2015)
  • Author(s): Kang, J.H., Asai, D., Toita, R., Kawano, T., and Murata, M.
  • Journal Title: Amino Acids Volume: 47 Issue: 11 Pages: 2377-2383
  • DOI: 10.1007/s00726-015-2025-y
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Systemic Delivery of Protein Nanocages Bearing CTT Peptides for Enhanced Imaging of MMP-2 Expression in Metastatic Tumor Models Authors (2014)
  • Author(s): Kawano T, Murata M, Piao J, Narahara S, Hamano N, Kang J, Hashizume M
  • Journal Title: Int J Mol Sci Volume: 16(1) Issue: 1 Pages: 148-158
  • DOI: 10.3390/ijms16010148
  • Peer Reviewed / Open Access
• [Journal Article] Expression and characterization of myristoylatedpreS1-conjugated nanocages for targeted cell delivery (2014)
  • Author(s): Murata M, Piao JS, Narahara S, Kawano T, Hamano N, Kang JH, Asai D, Ugawa R, Hashizume M,
  • Journal Title: Protein Expressionand Purification Volume: 110 Pages: 52-56
  • DOI: 10.1016/j.pep.2014.12.001
  • Peer Reviewed / Open Access
• [Presentation] Protein NanoCages Conjugated Magnetic Resonance Contrast Agents with High Relaxivity Properties (2017)
  • Author(s): Takahito Kawano, Masaharu Murata, Jeong-Hun Kang, Jing Shu Piao, Sayoko Narahara, Fuminori Hyodo, Nobuhito Hamano, Jie Guo, Susumu Oguri, Kenoki Ohuchida, Makoto Hashizume
  • Organizer: Biomaterials International 2018
  • Int'l Joint Research
• [Presentation] タンパク質ナノカプセルを用いたin vivo膵癌検出ナノMRI造影剤 (2016)
  • Author(s): 河野 喬仁・ 村田 正治・朴 晶淑・楢原 佐由子・濱野 展人・大内田 研宙・橋爪 誠
  • Organizer: DDS学会学術集会
  • Place of Presentation: 静岡市
  • Year and Date: 2016-06-30
• [Presentation] 膵癌特異的タンパク質ナノカプセルを用いた高感度MRI造影剤 (2015)
  • Author(s): 河野喬仁、村田正治、朴晶淑、楢原佐由子、大内田研宙、橋爪誠
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 東京都 新宿京王プラザホテル
  • Year and Date: 2015-07-02