Molecular Design of Nanostructures with High-Density Nucleic Acid Brushes for Carrier-Free DDS
| Project/Area Number |
17K05938
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bio-related chemistry
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
AKIYAMA YOSHITSUGU 東京理科大学, 基礎工学部教養(長万部), 准教授 (40640842)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | キャリアフリーDDS / DNA密生層 / ナノ構造体 / コンビネーション治療 / ナノ医療 / 自己崩壊性高分子 / 核酸医薬 / 分子標的医薬 / 刺激応答性高分子 / ドラッグデリバリーシステム / ナノバイオマテリアル / 生体材料 / がん化学療法 / 遺伝子治療 |
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| Outline of Final Research Achievements |
We developed spherical nucleic acids having a core structure of self-immolative polymer that can undergo disassembly through a self-immolative fragmentation. A poly(carbamate)（PC）derivative composed of 4-aminobenzyl alcohol as a repeat unit was treated with carbonyldiimidazole, followed by conjugation with DNA on a solid support to give a DNA-PC conjugate. Subsequent cleavage from the solid support and dialysis against water resulted in a self-assembly of DNA-PC conjugate with a narrow unimodal size distribution in DLS measurements, indicating formation of nanostructure covered with a dense DNA shell in aqueous solution. The nanostructure thus obtained may undergo domino-like disassembly of PC that can release 4-aminobenzyl alcohol at several triggers. More importantly, this methodology leads to the creation of carrier-free DDS by replacing each unit in the PC with a pharmaceutical drug having a 4-aminobenzyl alcohol substitution.
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| Academic Significance and Societal Importance of the Research Achievements |
核酸密生層の内殻を自己崩壊性高分子とする試みは既往研究がなく、外部刺激に呼応した特異崩壊性の精密制御は、ナノ医療だけでなくナノ界面科学における基礎と応用の双方にとって興味がもたれる。また、内殻を金ナノ粒子としたハイブリッド型ナノ材料は低分子医薬の活性を目視で迅速に判定できる簡易スクリーニング技術に応用できる。今後、内殻を形成する低分子医薬オリゴマーを目視探索技術で選択し、キャリアフリー型ナノDDS製剤に組み込むことによって、治療用途に応じた異種医薬の候補探索から治療までを一体化したナノ医療の発展に広く貢献できるものである。
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Report
(4 results)
Research Products
(24 results)
