Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F21%3A00124270" target="_blank" >RIV/00216224:14740/21:00124270 - isvavai.cz</a>
Result on the web
<a href="https://www.dovepress.com/passive-diffusion-vs-active-ph-dependent-encapsulation-of-tyrosine-kin-peer-reviewed-fulltext-article-IJN" target="_blank" >https://www.dovepress.com/passive-diffusion-vs-active-ph-dependent-encapsulation-of-tyrosine-kin-peer-reviewed-fulltext-article-IJN</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2147/IJN.S275808" target="_blank" >10.2147/IJN.S275808</a>
Alternative languages
Result language
angličtina
Original language name
Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LQ1601" target="_blank" >LQ1601: CEITEC 2020</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Journal of Nanomedicine
ISSN
1178-2013
e-ISSN
1176-9114
Volume of the periodical
16
Issue of the periodical within the volume
2021
Country of publishing house
NZ - NEW ZEALAND
Number of pages
14
Pages from-to
1-14
UT code for WoS article
000607548900001
EID of the result in the Scopus database
2-s2.0-85099919517