TY - JOUR
T1 - Heparin interferes with the uptake of liposomes in glioma
AU - van Solinge, Thomas S
AU - Friis, Kristina Pagh
AU - O'Brien, Killian
AU - Verschoor, Romy L
AU - van Aarle, Jeroen
AU - Koekman, Arnold
AU - Breakefield, Xandra O
AU - Vader, Pieter
AU - Schiffelers, Raymond
AU - Broekman, Marike
N1 - Funding Information:
Authors wish to thank Rosalie Schnoor and Koen Breyne for their scientific input and advice regarding this manuscript. The Breakefield lab receives funding from grant NCI CA069246 and CA232103 . Thomas van Solinge is supported by grants from the Bontius Stichting , the Nijbakker-Morra Fund , Foundation Vrijvrouwe van Renswoude and the Bekker-la Bastide Fund . Kristina Friis was supported by the Alfred Benzon Foundation .
Publisher Copyright:
© 2023 The Authors
PY - 2023/12/15
Y1 - 2023/12/15
N2 - In glioblastoma, a malignant primary brain tumor, liposomes have shown promise in pre-clinical and early phase clinical trials as delivery vehicles for therapeutics. However, external factors influencing cellular uptake of liposomes in glioma cells are poorly understood. Heparin and heparin analogues are commonly used in glioma patients to decrease the risk of thrombo-embolic events. Our results show that heparin inhibits pegylated liposome uptake by U87 glioma and GL261 cells in a dose dependent manner
in vitro, and that heparin-mediated inhibition of uptake required presence of fetal bovine serum in the media. In a subcutaneous model of glioma
, Cy5.5 labeled liposomes could be detected with
in vivo imaging after direct intra-tumoral injection.
Ex-vivo analysis with flow cytometry showed a decreased uptake of liposomes into tumor cells in mice treated systemically with heparin compared to those treated with vehicle only.
AB - In glioblastoma, a malignant primary brain tumor, liposomes have shown promise in pre-clinical and early phase clinical trials as delivery vehicles for therapeutics. However, external factors influencing cellular uptake of liposomes in glioma cells are poorly understood. Heparin and heparin analogues are commonly used in glioma patients to decrease the risk of thrombo-embolic events. Our results show that heparin inhibits pegylated liposome uptake by U87 glioma and GL261 cells in a dose dependent manner
in vitro, and that heparin-mediated inhibition of uptake required presence of fetal bovine serum in the media. In a subcutaneous model of glioma
, Cy5.5 labeled liposomes could be detected with
in vivo imaging after direct intra-tumoral injection.
Ex-vivo analysis with flow cytometry showed a decreased uptake of liposomes into tumor cells in mice treated systemically with heparin compared to those treated with vehicle only.
KW - Delivery
KW - Glioblastoma
KW - Glioma
KW - Heparin
KW - Liposomes
KW - Uptake
UR - http://www.scopus.com/inward/record.url?scp=85163197837&partnerID=8YFLogxK
U2 - 10.1016/j.ijpx.2023.100191
DO - 10.1016/j.ijpx.2023.100191
M3 - Article
C2 - 37408568
VL - 6
SP - 1
EP - 8
JO - International Journal of Pharmaceutics: X
JF - International Journal of Pharmaceutics: X
M1 - 100191
ER -