Development of Organic-Inorganic Hybrid Nucleic Acid Delivery System Toward the NAFLD/NASH Treatment
| Project/Area Number |
21K18064
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 水酸アパタイト / DDS / 高分子 / NASH / 免疫寛容 / HAp / 核酸医薬 / ナノテクノロジー |
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| Outline of Research at the Start |
非アルコール性脂肪性肝疾患(NAFLD)/非アルコール性脂肪性肝炎(NASH)は先進国における患者数増加が報告されており、進行すると肝硬変を誘導する基礎疾患である。申請者は、優れた核酸担持・エンドソーム脱出能を有する中空水酸アパタイト(HAp)ナノ粒子を、肝実質細胞特異性のあるガラクトースポリマーで被覆し、ガラクトースポリマーの肝実質細胞特異性とHApの核酸担持・エンドソーム脱出能を両立した核酸医薬送達キャリアを作製できると考えた。具体的には、肝細胞に特異的に吸着・貪食されるガラクトースポリマーを粒径50nm程度の中空HApナノ粒子に修飾することで、核酸医薬の肝実質細胞への送達を目指す。
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| Outline of Final Research Achievements |
Non-Alcoholic Fatty Liver Disease (NAFLD)/Non-Alcoholic Steatohepatitis (NASH) are underlying diseases inducing cirrhosis of the liver, with an increase in patient numbers reported in developed countries. We hypothesize that it's possible to create a nucleic acid drug delivery carrier that combines the liver parenchymal cell specificity of a galactose polymer with the nucleic acid carrying and endosomal escape abilities of hollow hydroxyapatite (HAp) nanoparticles. Specifically, we aim to deliver nucleic acid medicine to liver parenchymal cells by modifying hollow HAp nanoparticles, which are about 200nm in size, with a galactose polymer that is specifically adsorbed and ingested by liver cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、優れた核酸担持容量・核酸保護機能・エンドソーム脱出機能を持った中空ナノHAp、生体適合・肝細胞送達ブロックとHAp吸着ブロックからなるジブロック共重合体をそれぞれ設計した。これらの複合体に、NASHの治療に向けたIL-11 siRNAを搭載することで、効果的なNASH治療法の開発を目指す。本研究の独自性はナノスケールで形態が制御されたHAp中空ナノ粒子の設計と、高分子材料を用いたHAp表面の機能化技術である。
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Report
(3 results)
Research Products
(42 results)
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[Journal Article] Block catiomers with flanking hydrolyzable tyrosinate groups enhance in vivo mRNA delivery via マ?窶苫? stacking-assisted micellar assembly2023
Author(s)
Wenqian Yang, Takuya Miyazaki, Yasuhiro Nakagawa, Eger Boonstra, Keita Masuda, Yuki Nakashima, Pengwen Chen, Lucas Mixich, Kevin Barthelmes, Akira Matsumoto, Peng Mi, Satoshi Uchida, Horacio Cabral
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Journal Title
Science and technology of advanced materials
Volume: 24
Issue: 1
Pages: 2170164-2170164
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models2022
Author(s)
Panagi M, Mpekris F, Chen P, Voutouri C, Nakagawa Y, Martin J D., Hiroi T, Hashimoto H, Demetriou P, Pierides C, Samuel R, Stylianou A, Michael C, Fukushima S, Georgiou P, Papageorgis P, Papaphilippou P Ch., Koumas L, Costeas P, Ishii G, Kojima M, Kataoka K, Cabral H, Stylianopoulos T
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Journal Title
Nature Communications
Volume: 13
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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