Developing brain-penetrating anti-inflammatory nano-medicines to treat neurodegenerative diseases
| Project/Area Number |
18K14100
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 28040:Nanobioscience-related
|
|---|
| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
|---|
Principal Investigator |
Gonzalez Carter Daniel Angel 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (80800903)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | Nanoparticles / Brain / Blood-brain barrier / Glucose / Alzheimer's / Brain targeting / Brain vasculature label / mRNA delivery / Labelled proteins / BBB penetration / Nanomicelle / Protein loading / CD200 protein / Brain inflammation / Polymeric nano-micelles / Brain penetration / Anti-inflammation / Alzheimer's disease |
|---|
| Outline of Final Research Achievements |
We created a nano-carrier system capable of delivering therapeutic payloads specifically into the brain. We designed nanoparticles decorated with glucose (G-NP) capable of encapsulating therapeutic antibodies. By modulating blood-glucose levels, we were able to induce movement of the glucose transporter Glut-1 specifically across brain endothelial cells (BEC). Hence, the G-NP bound to the Glut-1 were transported across BEC to release their therapeutic cargo specifically in the brain. We demonstrated the therapeutic potential of this strategy by delivering antibodies capable of preventing aggregation of amyloid-beta, a key pathological mechanism in Alzheimer's disease.
We also developed a new brain-targeting strategy which exploits the impermeability of the blood-brain barrer to selectively label BEC. This strategy has the benefit that it does not modify the physiology of the organism, therefore has great potential for clinical translation.
|
| Academic Significance and Societal Importance of the Research Achievements |
Treating neurodegenerative diseases is severely limited by the poor entry of therapies into the brain. We have developed two different strategies capable of delivering nanoparticles specifically to the brain, thereby paving the way to deliver a wide-range of therapies into the brain.
|
Report
(4 results)
Research Products
(9 results)
-
-
[Journal Article] Dual-Sensitive Nanomicelles Enhancing Systemic Delivery of Therapeutically Active Antibodies Specifically into the Brain2020
Author(s)
Jinbing Xie, Daniel Gonzalez-Carter, Theofilus A. Tockary, Noriko Nakamura, Yonger Xue, Makoto Nakakido, Hiroki Akiba, Anjaneyulu Dirisala, Xueying Liu, Kazuko Toh, Tao Yang, Zengtao Wang, Shigeto Fukushima, Junjie Li, Sabina Quader, Kouhei Tsumoto, Takanori Yokota, Yasutaka Anraku*, and Kazunori Kataoka
-
Journal Title
ACS Nano
Volume: -
Issue: 6
Pages: 6729-6742
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
