| 研究実績の概要 |
We synthesized glucose decorated and epirubicin conjugated polymeric micelles that have pH-sensitive release profile. Epirubicin micelles had small size and uniform size distribution. We prepared epirubicin micelle decorated with different amount of glucose ( 0%, 25%, 50%, and 100%). The surface decoration of micelles by glucose molecule significantly affected their endocytosis, and fate in the cytoplasm. Specifically, glucose conjugated micelles are accompanied by exocytosis mechanism in parallel to endocytosis under monolayer cell culture condition with GLUT-1 overexpressed cell. Furthermore, under 3D multicellular tumor spheroid condition, this exocytosis mechanism of glucose micelles helps to drive the glucose micelles to penetrate deeper into tumor spheroid following transcytosis. And we observed, glucose epirubicin micelles having higher penetration than control micelles (that is 0% glucose decorated micelle). We confirmed that the epirubicin micelles with different amount of glucose decoration have long blood circulation property, which is one of the prerequisites for its therapeutic activities. We performed tumor accumulation and antitumor activity in an orthotopic breast cancer model. This tumor model had been selected as a pilot-study due to the fact that MDA-MB-231 cells overexpress GLUT1. We found significant difference between free epirubicin and epirubicin micelle groups. But no difference between the micelle groups was observed. Antitumor activity study against Glioblastoma models is currently undergoing.
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