Development of leukocyte-mimetic nanoparticles with ability to target and pass through the blood-brain barrier around the region of ischemic stroke

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16336
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: The University of Tokushima
• Principal Investigator: FUKUTA Tatsuya 徳島大学, 大学院医歯薬学研究部(薬学域), 助教 (90805160)
• Project Period (FY): 2019-04-01 – 2021-03-31
• 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

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.

Free Research Field

薬物送達学

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。