Development of leukocyte-mimetic nanoparticles with ability to target and pass through the blood-brain barrier around the region of ischemic stroke
| Project/Area Number |
19K16336
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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 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
FUKUTA Tatsuya 徳島大学, 大学院医歯薬学研究部(薬学域), 助教 (90805160)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | リポソーム / 脳梗塞 / 血液脳関門 / 白血球 / 脂質膜間移行 / バイオミメティック / 膜タンパク質 / がん / 脂質膜間移行法 / 炎症血管 / 脳血管内皮細胞 |
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| Outline of Research at the Start |
本研究では、白血球のように脳梗塞部位の血液脳関門（BBB）へ接着後、BBBを能動的に突破し、脳実質へ透過する白血球模倣ナノ粒子(Leukocyte-Mimetic NanoParticle; LM-NP)の開発を目指す。さらに、開発したLM-NPへBBB標的化素子を修飾することで、脳梗塞部位BBBへの高い標的性と突破能を有する革新的な脳梗塞治療用ナノ粒子を開発する。
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| Outline of Final Research Achievements |
Drug delivery using liposomes is useful for the treatment of cancer and ischemic stroke. However, since biological barriers such as vascular endothelial layer and tumor microenvironment often hamper liposome permeation into disease sites, new technologies which can overcome those barriers to enable efficient drug delivery have been desired. In this study, by focusing on leukocytes that can pass through tumor vessels and the blood-brain barrier (BBB) around ischemic stroke region, we prepared leukocyte-mimetic liposomes (LM-Lipo) by intermembrane protein transfer from leukemia cells and evaluated their function. LM-Lipo showed high affinity to inflamed human cerebral endothelial cells and lung cancer cells. Also, LM-lipo penetrated into tumor spheroids and showed high accumulation into tumor tissue of tumor-bearing mice. Based on these results, it is suggested that LM-Lipo could be a useful DDS carrier for cancer treatment, and that LM-Lipo might have a potential to target inflamed BBB.
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| Academic Significance and Societal Importance of the Research Achievements |
学術的意義として、本研究のさらなる発展は、ナノ粒子を用いたがん組織・脳梗塞部位への薬物送達における生体内の障壁、特に中枢創薬の最大の障壁であるBBBを克服し、新たなDDSの開発につながり得るとともに、生体機能を模倣したDDSの開発に向けた知見を提供できる点が挙げられる。また社会的意義として、脳梗塞やがんに対する新たな治療薬の開発に貢献でき、患者QOLの向上と、超高齢社会で問題とされる要介護人口の減少と医療経済の改善につながることが期待される。
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Report
(3 results)
Research Products
(24 results)
