초록 |
Glioblastoma multiforme (GBM), also known as Grade IV astrocytoma, is most aggressive malignant tumor in human beings. To cure GBM, we newly developed an orally absorbable heparin that can show antiangiogenic activity via binding with growth factors around tumor tissue. For this purpose, lactoferrin (Lf) was conjugated with heparin that is known as an anti-angiogenic molecules. This Lf can be orally absorbed by lactoferrin receptor (Lf-R) that is expressed on the intestine, blood-brain barrier and GBM. Through this study, we confirmed that conjugation between the Lf and heparin was successful as an amide bond, and this material inhibited angiogenesis effectively without toxicity on the in vitro model. In addition, when Lf-heparin was orally administered in the in vivo experiments, it was absorbed in the small intestine and delivered specifically to the brain. Also, we confirmed that Lf-heparin attenuated angiogenesis progression in the GBM orthotopic mouse model. |