Establishment of amino acid-capped metal nanoparticle for enhancing anti-protozoan activity

• Project/Area Number: 19K22940
• 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: Tohoku University
• Principal Investigator: KATO Kentaro 東北大学, 農学研究科, 教授 (30401178)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 金属ナノ粒子 / アミノ酸被膜 / 原虫 / 増殖抑制効果 / アミノ酸被膜金属ナノ粒子 / トキソプラズマ

Outline of Research at the Start

本研究ではトキソプラズマを寄生虫のモデルとして使用する。金属ナノ粒子としては、白金、金、銀の2種の合金、アミノ酸被膜した金属ナノ粒子を使用する。具体的には以下の項目について研究を行う。
(i)原虫感染細胞におけるアミノ酸被膜金属ナノ粒子の原虫増殖阻害効果の解析
(ii)金属ナノ粒子の哺乳類細胞（宿主細胞）への細胞毒性の解析
(iii)原虫のシスト（休眠型虫体）に対するナノ粒子の効果の解析
(iv)金属ナノ粒子の原虫増殖抑制メカニズムの解析

Outline of Final Research Achievements

Toxoplasma gondii causes toxoplasmosis, a common infection against which better drugs are needed. Recently, we showed that inorganic nanoparticles have anti-Toxoplasma activity. Here, we sought to enhance the anti-parasitic efficacy and host biocompatibility of these nanoparticles by modifying their surface with amino acids. Amino acid-capped nanoparticles (amino-NPs) were synthesized, purified, and then screened for anti-Toxoplasma activity in in vitro infection models. The amino-NPs showed enhanced anti-parasitic selectivity as well as improved host biocompatibility. Oxidative stress, modulation of host HIF-1α, and activation of the kynurenine pathway contributed to the anti-parasitic action of the amino-NPs.

Academic Significance and Societal Importance of the Research Achievements

トキソプラズマ症には全世界人口の約3割が潜伏感染状態と推定され、世界で広く分布しているが、現状のトキソプラズマ治療のための薬剤は限られていることから、代替薬が求められている。一方で、ナノテクノロジーの発展により同技術の医療への利用の可能性が期待され、様々な疾患に対する将来的な治療方法の１つとして研究が進められている。本研究の成果は、金属ナノ粒子を基にした新規の抗トキソプラズマ薬としての可能性だけでなく、抗原虫作用の分子メカニズムの解明に向けた新たな知見を提供する。粒子の大きさ、他の特性を変化させることで医学応用が図られ、特に活性酸素種の生成を促進することで病原体の殺傷に効果がある可能性がある。

Research Products

• [Int'l Joint Research] Landmark University(ナイジェリア)
• [Int'l Joint Research] LANDMARK UNIVERSITY(ナイジェリア)
• [Int'l Joint Research] 内モンゴル民族大学(中国)
• [Int'l Joint Research] LANDMARK UNIVERSITY(ナイジェリア)
• [Journal Article] The anti-parasite action of imidazole derivatives likely involves oxidative stress but not HIF-1α signaling (2021)
  • Author(s): Adeyemi Oluyomi Stephen、Eseola Abiodun Omokehinde、Plass Winfried、Kato Kentaro、Otuechere Chiagoziem A.、Awakan Oluwakemi Josephine、Atolani Olubunmi、Otohinoyi David Adeiza、Elebiyo Tobiloba Christiana、Evbuomwan Ikponmwosa Owen
  • Journal Title: Chemico-Biological Interactions Volume: 349 Pages: 109676-109676
  • DOI: 10.1016/j.cbi.2021.109676
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New Series of Imidazoles Showed Promising Growth Inhibitory and Curative Potential Against Trypanosoma Infection. (2021)
  • Author(s): 2)Adeyemi OS, Molefe-Nyembe NI, Eseola AO, Plass W, Shittu OK, Yunusa IO, Atolani O, Evbuomwan IO, Awakan OJ, Suganuma K, Kato K
  • Journal Title: Yale J Biol Med. Volume: 94 Pages: 199-207
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Screening of compound libraries for inhibitors of Toxoplasma growth and invasion (2020)
  • Author(s): Han Yongmei、Adeyemi Oluyomi Stephen、Kabir Mohammad Hazzaz Bin、Kato Kentaro
  • Journal Title: Parasitology Research Volume: 119 Issue: 5 Pages: 1675-1681
  • DOI: 10.1007/s00436-020-06673-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Imidazole derivatives as antiparasitic agents and use of molecular modeling to investigate the structure?activity relationship (2020)
  • Author(s): Adeyemi Oluyomi Stephen、Eseola Abiodun Omokehinde、Plass Winfried、Atolani Olubunmi、Sugi Tatsuki、Han Yongmei、Batiha Gaber El-saber、Kato Kentaro、Awakan Oluwakemi Josephine、Olaolu Tomilola Debby、Nwonuma Charles Obiora、Alejolowo Omokolade、Owolabi Akinyomade、Rotimi Damilare、Kayode Omowumi Titilola
  • Journal Title: Parasitology Research Volume: 119 Issue: 6 Pages: 1925-1941
  • DOI: 10.1007/s00436-020-06668-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nullscript inhibits Cryptosporidium and Toxoplasma growth (2020)
  • Author(s): Murakoshi Fumi、Bando Hironori、Sugi Tatsuki、Adeyemi Oluyomi Stephen、Nonaka Motohiro、Nakaya Takaaki、Kato Kentaro
  • Journal Title: International Journal for Parasitology: Drugs and Drug Resistance Volume: 14 Pages: 159-166
  • DOI: 10.1016/j.ijpddr.2020.10.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tree of motility;A proposed history of motility systems in the tree of life (2020)
  • Author(s): M Miyata, R C Robinson, T QP Uyeda, Y Fukumori, S Fukushima, S Haruta, M Homma, K Inaba, M Ito, C Kaito, K Kato, TKenri, Y Kinosita, S Kojima, T Minamino, H Mori, S Nakamura, D Nakane, K Nakayama, M Nishiyama, S Shibata, K Shimabukuro, M Tamakoshi, A Taoka, Y Tashiro, ITulum, HiWada, K Wakabayashi
  • Journal Title: Genes to Cells Volume: 25 Issue: 1 Pages: 6-21
  • DOI: 10.1111/gtc.12737
  • NAID: 120006881482
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nanoparticles show potential to retard bradyzoites in vitro formation of Toxoplasma gondii (2019)
  • Author(s): Adeyemi Oluyomi Stephen、Murata Yuho、Sugi Tatsuki、Han Yongmei、Kato Kentaro
  • Journal Title: Folia Parasitologica Volume: 66
  • DOI: 10.14411/fp.2019.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The pathogenesis and clinical manifestations of and anti-parasitic drug development for malaria and toxoplasmosis. (2021)
  • Author(s): Kentaro Kato
  • Organizer: The symposium of the Korean society for parasitology 2021
  • Int'l Joint Research / Invited
• [Presentation] ヒトの脳神経細胞内におけるトキソプラズマのステージ変換メカニズムの解明 (2020)
  • Author(s): 伴戸寛徳、福田康弘、加藤健太郎
  • Organizer: 第89回日本寄生虫学会大会
• [Presentation] ヒトの脳細胞における宿主-トキソプラズマ間相互作用の解明 (2020)
  • Author(s): 伴戸寛徳、福田康弘、山本雅裕、加藤健太郎
  • Organizer: 第163回日本獣医学会
  • Invited
• [Book] 「JVPA DIGEST」 原虫の感染・増殖メカニズムと抗原虫薬の開発について (2020)
  • Author(s): 加藤健太郎
  • Total Pages: 43
  • Publisher: 公益社団法人 日本動物用医薬品協会
  • ISBN: 4820494171
• [Book] 金属ナノ粒子の抗原虫効果とアミノ酸被膜による向上「BIO INDUSTRY」 (2019)
  • Author(s): 加藤健太郎
  • Total Pages: 90
  • Publisher: シーエムシー出版
• [Remarks] 東北大学大学院農学研究科動物環境管理学分野のホームページ
  • URL: https://www.agri.tohoku.ac.jp/health/index.html
• [Remarks] 東北大学大学院農学研究科動物環境システム学分野のホームページ
  • URL: https://www.agri.tohoku.ac.jp/health/index.html
• [Remarks] https://www.agri.tohoku.ac.jp/health/index.html