Therapeutic Effect of Cabazitaxel and Blood-Brain Barrier opening in a Patient-Derived Glioblastoma Model

Sulheim, Einar; Mørch, Yrr; Snipstad, Sofie; Borgos, Sven Even; Miletic, Hrvoje; Bjerkvig, Rolf; Davies, Catharina de Lange; Åslund, Andreas K.O.

doi:10.7150/ntno.31479

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Nanotheranostics 2019; 3(1):103-112. doi:10.7150/ntno.31479 This issue Cite

Research Paper

Therapeutic Effect of Cabazitaxel and Blood-Brain Barrier opening in a Patient-Derived Glioblastoma Model

Einar Sulheim^1,2,3✉, Yrr Mørch², Sofie Snipstad^1,2,3, Sven Even Borgos², Hrvoje Miletic^4,5, Rolf Bjerkvig^5,6, Catharina de Lange Davies¹, Andreas K.O. Åslund^1,2,7

1. Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
2. Department of Biotechnology and Nanomedicine, SINTEF AS, Trondheim Norway
3. Cancer Clinic, St.Olav's University Hospital, Trondheim Norway
4. Department of Pathology, Haukeland University Hospital, Bergen, Norway
5. Department of Biomedicine, University of Bergen, Norway
6. Department of Oncology, Luxembourg Institute of Health, Luxembourg
7. Stroke Unit, Department of internal medicine, St. Olav's University Hospital, Trondheim, Norway

Citation:

Sulheim E, Mørch Y, Snipstad S, Borgos SE, Miletic H, Bjerkvig R, Davies CdL, Åslund AKO. Therapeutic Effect of Cabazitaxel and Blood-Brain Barrier opening in a Patient-Derived Glioblastoma Model. Nanotheranostics 2019; 3(1):103-112. doi:10.7150/ntno.31479. https://www.ntno.org/v03p0103.htm

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Abstract

Treatment of glioblastoma and other diseases in the brain is especially challenging due to the blood-brain barrier, which effectively protects the brain parenchyma. In this study we show for the first time that cabazitaxel, a semi-synthetic derivative of docetaxel can cross the blood-brain barrier and give a significant therapeutic effect in a patient-derived orthotopic model of glioblastoma. We show that the drug crosses the blood-brain barrier more effectively in the tumor than in the healthy brain due to reduced expression of p-glycoprotein efflux pumps in the vasculature of the tumor. Surprisingly, neither ultrasound-mediated blood-brain barrier opening (sonopermeation) nor drug formulation in polymeric nanoparticles could increase either accumulation of the drug in the brain or therapeutic effect. This indicates that for hydrophobic drugs, sonopermeation of the blood brain barrier might not be sufficient to achieve improved drug delivery. Nonetheless, our study shows that cabazitaxel is a promising drug for the treatment of brain tumors.

Keywords: cabazitaxel, glioblastoma, orthotopic model, sonopermeation

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APA

Sulheim, E., Mørch, Y., Snipstad, S., Borgos, S.E., Miletic, H., Bjerkvig, R., Davies, C.d.L., Åslund, A.K.O. (2019). Therapeutic Effect of Cabazitaxel and Blood-Brain Barrier opening in a Patient-Derived Glioblastoma Model. Nanotheranostics, 3(1), 103-112. https://doi.org/10.7150/ntno.31479.

ACS

Sulheim, E.; Mørch, Y.; Snipstad, S.; Borgos, S.E.; Miletic, H.; Bjerkvig, R.; Davies, C.d.L.; Åslund, A.K.O. Therapeutic Effect of Cabazitaxel and Blood-Brain Barrier opening in a Patient-Derived Glioblastoma Model. Nanotheranostics 2019, 3 (1), 103-112. DOI: 10.7150/ntno.31479.

NLM

CSE

Sulheim E, Mørch Y, Snipstad S, Borgos SE, Miletic H, Bjerkvig R, Davies CdL, Åslund AKO. 2019. Therapeutic Effect of Cabazitaxel and Blood-Brain Barrier opening in a Patient-Derived Glioblastoma Model. Nanotheranostics. 3(1):103-112.

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