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- Title
Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome.
- Authors
Ferber, Shiran; Tiram, Galia; Sousa-Herves, Ana; Eldar-Boock, Anat; Krivitsky, Adva; Scomparin, Anna; Yeini, Eilam; Ofek, Paula; Ben-Shushan, Dikla; Vossen, Laura Isabel; Kai Licha; Grossman, Rachel; Ram, Zvi; Henkin, Jack; Ruppin, Eytan; Auslander, Noam; Haag, Rainer; Calderón, Marcelo; Satchi-Fainaro, Ronit
- Abstract
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 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 free PTX or temozolomide. This study shows that our unique therapeutic approach offers a viable alternative for the treatment of glioblastoma.
- Subjects
GLIOBLASTOMA multiforme treatment; BLOOD-brain barrier; PACLITAXEL; CANCER chemotherapy; NANOCARRIERS; ENDOTHELIUM
- Publication
eLife, 2017, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.25281