Specificity of brain tumor capillaries and novel drug delivery system

Abstract

The survival rate of patients with malignant glioma is still low. Because of the existence of blood-brain barrier (BBB) and the blood-tumor barrier, the delivery of anticancer agents is limited in the central nervous system. To overcome this problem, establishment of new targets for anticancer therapy and new drug delivery systems is important. The expression of various vascular growth factors in human brain tumors was examined in this study. Vascular endothelial growth factor (VEGF) might be a new candidate for anti-glioma therapy because it is deeply involved in angiogenesis occurring in malignant gliomas. The properties of brain tumor capillaries with regard to BBB-specific structure and function were also investigated. Gliomas had relatively well preserved BBB structure and function in their capillary endothelial cells. To overcome the blood-tumor barrier and to establish a new drug delivery system, we examined the effects of intracarotid infusion of various vasoactive agents on regional blood flow and capillary permeability in normal and tumor tissue in an animal model. Intracarotid infusion of bradykinin seemed to be the most promising drug delivery system for glioma, making it possible to deliver various anticancer agents selectively to malignant gliomas. Combining these approaches may lead to more effective and selective anti-glioma therapy in the near future.