TY - JOUR
T1 - 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
N1 - Publisher Copyright:
© Ferber et al.
PY - 2017/10/4
Y1 - 2017/10/4
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85036508928&partnerID=8YFLogxK
U2 - 10.7554/eLife.25281
DO - 10.7554/eLife.25281
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AN - SCOPUS:85036508928
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e25281
ER -