TY - JOUR TI - Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome AU - Ferber, Shiran AU - Tiram, Galia AU - Sousa-Herves, Ana AU - Eldar-Boock, Anat AU - Krivitsky, Adva AU - Scomparin, Anna AU - Yeini, Eilam AU - Ofek, Paula AU - Ben-Shushan, Dikla AU - Vossen, Laura Isabel AU - Licha, Kai AU - Grossman, Rachel AU - Ram, Zvi AU - Henkin, Jack AU - Ruppin, Eytan AU - Auslander, Noam AU - Haag, Rainer AU - Calderón, Marcelo AU - Satchi-Fainaro, Ronit A2 - Sawyers, Charles L VL - 6 PY - 2017 DA - 2017/10/04 SP - e25281 C1 - eLife 2017;6:e25281 DO - 10.7554/eLife.25281 UR - https://doi.org/10.7554/eLife.25281 AB - 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. KW - P/L-selectins KW - glioblastoma KW - targeted delivery KW - polymeric nanomedicine KW - polyglycerol KW - thrombospondin-1 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -