2017 Fiscal Year Annual Research Report
細胞内標的化スマートナノDDSを用いた効率的かつ安全ながんワクチンの開発
| Project/Area Number |
17F17035
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine |
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Principal Investigator |
Quader Sabina 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, 主任研究員 (90749699)
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| Co-Investigator(Kenkyū-buntansha) |
MAITY AMIT 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, 外国人特別研究員
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| Project Period (FY) |
2017-04-26 – 2019-03-31
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| Keywords | Glioblastoma / Polymer Micelle / Epirubicin / Ligand / pH sensitive |
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| Outline of Annual Research Achievements |
The main purpose of the research project is to develop Glucose decorated and Epirubicin loaded polymeric micelle system for targeting glioblastoma. Glioblastoma (GBM) is the most deadly and prevalent form of brain tumor; with current treatment routine only >5% of patients with GBM survive longer than 3 years. There is thus a pressing need to develop efficient treatment of GBM.
Here are the current research achievements towards achieving the purpose of the research.
Developed skills for polymer synthesis. 2. Developed ligand and drug conjugation chemistry. 3. Prepared particles with different fraction of Glucose (0%, 25% and 50%). 4. Confirmed physicochemical properties of the Glucose decorated particles, for example, size, polydisparsity and drug release mechanism. 5. Cell internalization in 2D cell culture condition was evaluated. Developed and validated method for quantification of cellular uptake (monolayer) . 6. To study particle penetration ability in 3D cell culture condition, a robust protocol was developed to prepare spheroids. Additionally penetration behavior (spheroids) using pixel-by-pixel analysis of each confocal images of each cell was developed. We confirmed that GLUT1 mediated endocytosis of glucose micelles is accompanied by exocytosis mechanism in parallel (i.e. transcytosis). And this behavior was not observed for non-glucose micelles. We also confirmed that glucose micelles exhibit higher penetration in spheroids than non-glucose micelles.
Regularly presented research result within research group.
Presented research result in scientific conference.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
We successfully developed and scale up the synthesis scheme to prepared glucose-epirubicin micelles (Glucose-Epi/m) with varying glucose density and evaluated their uptake and penetration profile in 2D and 3D culture condition respectively. For this purpose, we used MDA-MB-231 (as GLUT1 overexpressed) and U87-MG (as control) cell lines. We have achieved important and useful research results in 2D and 3D cell culture model for evaluating the penetration profile of glucose installed epirubicin micelles. For this work, a concrete protocol to prepare spheroids routinely has been developed. We extended the condition for co-cultured spheroids of two cell lines; for example a glioma cell line U87MG and Human Umbilical Vein Endothelial Cells, HUVEC. Also, developed and validated method for quantification of cellular uptake (in 2D culture) and penetration behavior (in 3D spheroids) using pixel-by-pixel analysis of each confocal images of each cell. We are planning to conduct anti-tumor activity and tumor accumulation studies in the coming months.
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| Strategy for Future Research Activity |
1. Multicellular tumor spheroids treated with micelles to check its efficacy will be continued.
2. Cytotoxicity study of tumor spheroids will be conducted.
3. Anti-tumor activity will be evaluated against a Glioblastoma tumor model.
4. Tumor accumulation studies of the ligand-decorated micelle will be conducted.
5. Density of the ligand on the surface will be fine-tuned to achieve maximum biological efficacy.
6. Pharmacokinetics and pharmacodynamics of the Epirubicin loaded ligand decorated micelle will be evaluated. 7. Manuscript preparation will be continued.
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Research Products
(1 results)
