VEGF-mediated tight junctions pathological fenestration enhances doxorubicin-loaded glycolipid-like nanoparticles traversing BBB for glioblastoma-targeting therapy.

ABSTRACT: The existence of blood-brain barrier (BBB) greatly hindered the penetration and accumulation of chemotherapeutics into glioblastoma (GBM), accompany with poor therapeutic effects. The growth of GBM supervene the impairment of tight junctions (TJs); however, the pathogenesis of BBB breakdown in GBM is essentially poorly understood. This study found that vascular endothelial growth factor (VEGF) secreted by GBM cells plays an important role in increasing the permeability of BBB by disrupting endothelial tight junction proteins claudin-5 and thus gave doxorubicin (DOX)-loaded glycolipid-like nanoparticles (Ap-CSSA/DOX), an effective entrance to brain tumor region for GBM-targeting therapy. In addition, VEGF downregulates the expression of claudin-5 with a dose-dependent mode, and interfering

SUBMITTER: Wen L 

PROVIDER: S-EPMC8241127 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature