Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib
A tyrosine kinase inhibitor, vandetanib (Van), is an anticancer drug affecting the signaling of VEGFR, EGFR and RET protooncogenes. Van is primarily used for the treatment of advanced or metastatic medullary thyroid cancer; however, its usage is significantly limited by side effects, particularly ca...
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2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/8/4250 |
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| author | Kateřina Jáklová Tereza Feglarová Simona Rex Zbyněk Heger Tomáš Eckschlager Jan Hraběta Petr Hodek Matúš Kolárik Radek Indra |
| author_facet | Kateřina Jáklová Tereza Feglarová Simona Rex Zbyněk Heger Tomáš Eckschlager Jan Hraběta Petr Hodek Matúš Kolárik Radek Indra |
| author_sort | Kateřina Jáklová |
| collection | DOAJ |
| description | A tyrosine kinase inhibitor, vandetanib (Van), is an anticancer drug affecting the signaling of VEGFR, EGFR and RET protooncogenes. Van is primarily used for the treatment of advanced or metastatic medullary thyroid cancer; however, its usage is significantly limited by side effects, particularly cardiotoxicity. One approach to minimize them is the encapsulation or binding of Van in- or onto a suitable carrier, allowing targeted delivery to tumor tissue. Herein, we constructed a nanocarrier based on apoferritin associated with Van (ApoVan). Based on the characteristics obtained by analyzing the average size, the surface ζ-potential and the polydispersive index, ApoVan nanoparticles exhibit long-term stability and maintain their morphology. Experiments have shown that ApoVan complex is relatively stable during storage. It was found that Van is gradually released from its ApoVan form into the neutral environment (pH 7.4) as well as into the acidic environment (pH 6.5). The effect of free Van and ApoVan on neuroblastoma and medullary thyroid carcinoma cell lines revealed that both forms were toxic in both used cell lines, and minimal differences between ApoVan and Van were observed. Thus, we assume that Van might not be encapsulated into the cavity of apoferritin, but instead only binds to its surface. |
| first_indexed | 2024-03-10T12:10:24Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:10:24Z |
| publishDate | 2021-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-396c504b67bd4c449cfa0abb83b41c122023-11-21T16:15:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228425010.3390/ijms22084250Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of VandetanibKateřina Jáklová0Tereza Feglarová1Simona Rex2Zbyněk Heger3Tomáš Eckschlager4Jan Hraběta5Petr Hodek6Matúš Kolárik7Radek Indra8Department of Biochemistry, Faculty of Science, Charles University, Albertov 6, 128 00 Prague 2, Czech RepublicDepartment of Biochemistry, Faculty of Science, Charles University, Albertov 6, 128 00 Prague 2, Czech RepublicDepartment of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, 613 00 Brno, Czech RepublicDepartment of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, 613 00 Brno, Czech RepublicDepartment of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84/1, 150 06 Prague 5, Czech RepublicDepartment of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84/1, 150 06 Prague 5, Czech RepublicDepartment of Biochemistry, Faculty of Science, Charles University, Albertov 6, 128 00 Prague 2, Czech RepublicDepartment of Biochemistry, Faculty of Science, Charles University, Albertov 6, 128 00 Prague 2, Czech RepublicDepartment of Biochemistry, Faculty of Science, Charles University, Albertov 6, 128 00 Prague 2, Czech RepublicA tyrosine kinase inhibitor, vandetanib (Van), is an anticancer drug affecting the signaling of VEGFR, EGFR and RET protooncogenes. Van is primarily used for the treatment of advanced or metastatic medullary thyroid cancer; however, its usage is significantly limited by side effects, particularly cardiotoxicity. One approach to minimize them is the encapsulation or binding of Van in- or onto a suitable carrier, allowing targeted delivery to tumor tissue. Herein, we constructed a nanocarrier based on apoferritin associated with Van (ApoVan). Based on the characteristics obtained by analyzing the average size, the surface ζ-potential and the polydispersive index, ApoVan nanoparticles exhibit long-term stability and maintain their morphology. Experiments have shown that ApoVan complex is relatively stable during storage. It was found that Van is gradually released from its ApoVan form into the neutral environment (pH 7.4) as well as into the acidic environment (pH 6.5). The effect of free Van and ApoVan on neuroblastoma and medullary thyroid carcinoma cell lines revealed that both forms were toxic in both used cell lines, and minimal differences between ApoVan and Van were observed. Thus, we assume that Van might not be encapsulated into the cavity of apoferritin, but instead only binds to its surface.https://www.mdpi.com/1422-0067/22/8/4250vandetanibapoferritinneuroblastomamedullary thyroid cancercancer targeting |
| spellingShingle | Kateřina Jáklová Tereza Feglarová Simona Rex Zbyněk Heger Tomáš Eckschlager Jan Hraběta Petr Hodek Matúš Kolárik Radek Indra Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib International Journal of Molecular Sciences vandetanib apoferritin neuroblastoma medullary thyroid cancer cancer targeting |
| title | Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib |
| title_full | Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib |
| title_fullStr | Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib |
| title_full_unstemmed | Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib |
| title_short | Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib |
| title_sort | apoferritin vandetanib association is long term stable but does not improve pharmacological properties of vandetanib |
| topic | vandetanib apoferritin neuroblastoma medullary thyroid cancer cancer targeting |
| url | https://www.mdpi.com/1422-0067/22/8/4250 |
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