Passive diffusion vs. active pH-dependent encapsulation of tyrosine kinase inhibitors vandetanib and lenvatinib into folate-targeted ferritin delivery system

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dc.contributor.authorŠkubalová, Zuzanacs
dc.contributor.authorRex, Simonacs
dc.contributor.authorSúkupová, Martinacs
dc.contributor.authorZahálka, Martincs
dc.contributor.authorSkládal, Petrcs
dc.contributor.authorPřibyl, Jancs
dc.contributor.authorMichálková, Hanacs
dc.contributor.authorWeerasekera, Akilacs
dc.contributor.authorAdam, Vojtěchcs
dc.contributor.authorHeger, Zbyněkcs
dc.coverage.issue1cs
dc.coverage.volume16cs
dc.date.accessioned2021-05-06T10:55:02Z
dc.date.available2021-05-06T10:55:02Z
dc.date.issued2021-02-02cs
dc.description.abstractIntroduction: The present study reports on examination of the effects of encapsulating the tyrosine kinase inhibitors (TKIs) vandetanib and lenvatinib into a biomacromolecular ferritin-based delivery system. Methods: The encapsulation of TKIs was performed via two strategies: i) using an active reversible pH-dependent reassembly of ferritin's quaternary structure and ii) passive loading of hydrophobic TKIs through the hydrophobic channels at the junctions of ferritin subunits. After encapsulation, ferritins were surface-functionalized with folic acid promoting active-targeting capabilities. Results: The physico-chemical and nanomechanical analyses revealed that despite the comparable encapsulation efficiencies of both protocols, the active loading affects stability and rigidity of ferritins, plausibly due to their imperfect reassembly. Biological experiments with hormone-responsive breast cancer cells (T47-D and MCF-7) confirmed the cytotoxicity of encapsulated and folate-targeted TKIs to folate-receptor positive cancer cells, but only limited cytotoxic effects to healthy breast epithelium. Importantly, the long-term cytotoxic experiments revealed that compared to the pH-dependent encapsulation, the passively-loaded TKIs exert markedly higher anticancer activity, most likely due to undesired influence of harsh acidic environment used for the pH-dependent encapsulation on the TKIs' structural and functional properties. Conclusion: Since the passive loading does not require a reassembly step for which acids are needed, the presented investigation serves as a solid basis for future studies focused on encapsulation of small hydrophobic molecules.en
dc.formattextcs
dc.format.extent1-14cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationInternational Journal of Nanomedicine. 2021, vol. 16, issue 1, p. 1-14.en
dc.identifier.doi10.2147/IJN.S275808cs
dc.identifier.issn1178-2013cs
dc.identifier.other168946cs
dc.identifier.urihttp://hdl.handle.net/11012/196711
dc.language.isoencs
dc.publisherDove Medical Presscs
dc.relation.ispartofInternational Journal of Nanomedicinecs
dc.relation.urihttps://www.dovepress.com/passive-diffusion-vs-active-ph-dependent-encapsulation-of-tyrosine-kin-peer-reviewed-article-IJNcs
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unportedcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1178-2013/cs
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/cs
dc.subjectdrug deliveryen
dc.subjectnanomedicineen
dc.subjectlenvatiniben
dc.subjectvandetaniben
dc.titlePassive diffusion vs. active pH-dependent encapsulation of tyrosine kinase inhibitors vandetanib and lenvatinib into folate-targeted ferritin delivery systemen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-168946en
sync.item.dbtypeVAVen
sync.item.insts2021.05.06 12:55:02en
sync.item.modts2021.05.06 12:14:54en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Chytré nanonástrojecs
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