Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome

Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome

Blog Article

Glioblastoma is a highly aggressive brain tumor.Current standard-of-care results in a marginal therapeutic outcome, partly due to acquirement of resistance and insufficient blood-brain barrier (BBB) penetration of chemotherapeutics.To circumvent these limitations, we conjugated the chemotherapy color touch 7/97 paclitaxel (PTX) to a dendritic polyglycerol sulfate (dPGS) nanocarrier.dPGS is able to cross the BBB, bind to P/L-selectins and accumulate selectively in intracranial tumors.We show that dPGS has dual targeting properties, as we found that P-selectin is not only expressed on tumor endothelium but also on glioblastoma cells.

We delivered dPGS-PTX in combination with a peptidomimetic of the anti-angiogenic protein thrombospondin-1 (TSP-1 PM).This combination resulted in a remarkable synergistic anticancer effect on intracranial human and murine glioblastoma via induction of Fas and Fas-L, with no side effects compared to napoleon concealer free PTX or temozolomide.This study shows that our unique therapeutic approach offers a viable alternative for the treatment of glioblastoma.