期刊
ELIFE
卷 6, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.25281
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资金
- German-Israel Foundation (GIF)
- Tel Aviv University
- Freie Universitht Berlin
- European Research Council under the European Union's Seventh Framework Programme (FP)/ERC Consolidator Grant [617445]
- Israel Science Foundation [918/14]
- Nancy and Peter Brown friends of the Israel Cancer Association ICA USA
- Morris Kahn Foundation
- Bundesmiminsterium fur Bildung und Forschung (BMBF) within the Biotransporter project [13N11536, SFB 765]
- BMBF through the NanoMatFutur award [13N12561]
- focus area Nanoscale of the Freie Universitht Berlin
- Marie Curie lntra-European Fellowship [302717]
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.
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