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dc.contributor.authorFusser, Markus
dc.contributor.authorØverbye, Anders
dc.contributor.authorPandya, Abhilash D.
dc.contributor.authorMørch, Ýrr Asbjørg
dc.contributor.authorBorgos, Sven Even F.
dc.contributor.authorKildal, Wanja
dc.contributor.authorSnipstad, Sofie
dc.contributor.authorSulheim, Einar
dc.contributor.authorFleten, Karianne Giller
dc.contributor.authorAskautrud, Hanne Arenberg
dc.contributor.authorEngebraaten, Olav
dc.contributor.authorFlatmark, Kjersti
dc.contributor.authorIversen, Tore Geir
dc.contributor.authorSandvig, Kirsten
dc.contributor.authorSkotland, Tore
dc.contributor.authorMælandsmo, Gunhild Mari
dc.date.accessioned2019-01-07T12:40:05Z
dc.date.available2019-01-07T12:40:05Z
dc.date.issued2018-12-04
dc.description.abstractThe effect of poly(2-ethyl-butyl cyanoacrylate) nanoparticles containing the cytotoxic drug cabazitaxel was studied in three breast cancer cell lines and one basal-like patient-derived xenograft model grown in the mammary fat pad of immunodeficient mice. Nanoparticle-encapsulated cabazitaxel had a much better efficacy than similar concentrations of free drug in the basal-like patient-derived xenograft and resulted in complete remission of 6 out of 8 tumors, whereas free drug gave complete remission only with 2 out of 9 tumors. To investigate the different efficacies obtained with nanoparticle-encapsulated versus free cabazitaxel, mass spectrometry quantification of cabazitaxel was performed in mice plasma and selected tissue samples. Nanoparticle-encapsulated drug had a longer circulation time in blood. There was approximately a three times higher drug concentration in tumor tissue 24 h after injection, and two times higher 96 h after injection of nanoparticles with drug compared to the free drug. The tissue biodistribution obtained after 24 h using mass spectrometry analyses correlates well with biodistribution data obtained using IVIS® Spectrum in vivo imaging of nanoparticles labeled with the fluorescent substance NR668, indicating that these data also are representative for the nanoparticle distribution. Furthermore, immunohistochemistry was used to estimate infiltration of macrophages into the tumor tissue following injection of nanoparticle-encapsulated and free cabazitaxel. The higher infiltration of anti-tumorigenic versus pro-tumorigenic macrophages in tumors treated with the nanoparticles might also contribute to the improved effect obtained with the nanoparticle-encapsulated drug. Tumor infiltration of pro-tumorigenic macrophages was four times lower when using nanoparticles containing cabazitaxel than when using particles without drug, and we speculate that the very good therapeutic efficacy obtained with our cabazitaxel-containing particles may be due to their ability to reduce the level of pro-tumorigenic macrophages in the tumor. In summary, encapsulation of cabazitaxel in poly(2-ethyl-butyl cyanoacrylate) nanoparticles seems promising for treatment of breast cancer.en_US
dc.descriptionSource at <a href=https://doi.org/10.1016/j.jconrel.2018.11.029> https://doi.org/10.1016/j.jconrel.2018.11.029</a>. Licensed <a href=http://creativecommons.org/licenses/by-nc-nd/4.0/> CC BY-NC-ND 4.0.</a>en_US
dc.identifier.citationFusser, M., Øverbye, A., Pandya, A.D., Mørch, Y.A., Borgos, S.E., Kildal, W., ... Mælandsmo, G.M. (2018). Cabazitaxel-loaded Poly(2-ethylbutyl cyanoacrylate) nanoparticles improve treatment efficacy in a patient derived breast cancer xenograft. <i>Journal of Controlled Release</i>, 293, 183-192. https://doi.org/10.1016/j.jconrel.2018.11.029en_US
dc.identifier.cristinIDFRIDAID 1646220
dc.identifier.doi10.1016/j.jconrel.2018.11.029
dc.identifier.issn0168-3659
dc.identifier.issn1873-4995
dc.identifier.urihttps://hdl.handle.net/10037/14386
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalJournal of Controlled Release
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/NANO2021/228200/Norway/Biodegradable Nanoparticles in Cancer Diagnosis and Therapy//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.titleCabazitaxel-loaded Poly(2-ethylbutyl cyanoacrylate) nanoparticles improve treatment efficacy in a patient derived breast cancer xenograften_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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