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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.accessioned2019-03-06T12:58:45Z
dc.date.available2019-03-06T12:58:45Z
dc.date.created2018-12-20T13:03:51Z
dc.date.issued2018
dc.identifier.citationJournal of Controlled Release. 2018, 293 183-192.nb_NO
dc.identifier.issn0168-3659
dc.identifier.urihttp://hdl.handle.net/11250/2589028
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.nb_NO
dc.language.isoengnb_NO
dc.publisherElseviernb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleCabazitaxel-loaded Poly(2-ethylbutyl cyanoacrylate) nanoparticles improve treatment efficacy in a patient derived breast cancer xenograftnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumber183-192nb_NO
dc.source.volume293nb_NO
dc.source.journalJournal of Controlled Releasenb_NO
dc.identifier.doi10.1016/j.jconrel.2018.11.029
dc.identifier.cristin1646220
dc.relation.projectNorges forskningsråd: 228200nb_NO
dc.description.localcode© 2018 Oslo University Hospital. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).nb_NO
cristin.unitcode194,66,20,0
cristin.unitnameInstitutt for fysikk
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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