INTRODUCTION: 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.

• Klíčová slova
• drug delivery, lenvatinib, nanomedicine, vandetanib,
• MeSH
• antitumorózní látky farmakologie   MeSH
• biokompatibilní materiály chemie   MeSH
• buněčná smrt účinky léků   MeSH
• buněčné klony MeSH
• buněčné linie MeSH
• chinazoliny chemie   farmakologie   MeSH
• chinoliny chemie   farmakologie   MeSH
• difuze MeSH
• fenylmočovinové sloučeniny chemie   farmakologie   MeSH
• ferritin chemie   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• koncentrace vodíkových iontů MeSH
• koně MeSH
• kyselina listová chemie   MeSH
• lidé MeSH
• nosiče léků chemie   MeSH
• piperidiny chemie   farmakologie   MeSH
• pohyb buněk účinky léků   MeSH
• povrchové vlastnosti MeSH
• systémy cílené aplikace léků * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• biokompatibilní materiály MeSH
• chinazoliny MeSH
• chinoliny MeSH
• fenylmočovinové sloučeniny MeSH
• ferritin MeSH
• inhibitory proteinkinas MeSH
• kyselina listová MeSH
• lenvatinib MeSH Prohlížeč
• nosiče léků MeSH
• piperidiny MeSH
• vandetanib MeSH Prohlížeč