Apoferritin as an ubiquitous nanocarrier with excellent shelf life

Simona Dostalova,1,2 Katerina Vasickova,1 David Hynek,1,2 Sona Krizkova,1,2 Lukas Richtera,1,2 Marketa Vaculovicova,1,2 Tomas Eckschlager,3 Marie Stiborova,4 Zbynek Heger,1,2 Vojtech Adam1,2 1Department of Chemistry and Biochemistry, Mendel University in Brno, 2Central European Institute of Technol...

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Autores principales: Dostalova S, Vasickova K, Hynek D, Krizkova S, Richtera L, Vaculovicova M, Eckschlager T, Stiborova M, Heger Z, Adam V
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Lenguaje:EN
Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:298a996171f54374a6ce7ba35af2119b2021-12-02T07:44:03ZApoferritin as an ubiquitous nanocarrier with excellent shelf life1178-2013https://doaj.org/article/298a996171f54374a6ce7ba35af2119b2017-03-01T00:00:00Zhttps://www.dovepress.com/apoferritin-as-an-ubiquitous-nanocarrier-with-excellent-shelf-life-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Simona Dostalova,1,2 Katerina Vasickova,1 David Hynek,1,2 Sona Krizkova,1,2 Lukas Richtera,1,2 Marketa Vaculovicova,1,2 Tomas Eckschlager,3 Marie Stiborova,4 Zbynek Heger,1,2 Vojtech Adam1,2 1Department of Chemistry and Biochemistry, Mendel University in Brno, 2Central European Institute of Technology, Brno University of Technology, Brno, 3Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, University Hospital Motol, Charles University, 4Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic Abstract: Due to many adverse effects of conventional chemotherapy, novel methods of targeting drugs to cancer cells are being investigated. Nanosize carriers are a suitable platform for this specific delivery. Herein, we evaluated the long-term stability of the naturally found protein nanocarrier apoferritin (Apo) with encapsulated doxorubicin (Dox). The encapsulation was performed using Apo’s ability to disassemble reversibly into its subunits at low pH (2.7) and reassemble in neutral pH (7.2), physically entrapping drug molecules in its cavity (creating ApoDox). In this study, ApoDox was prepared in water and phosphate-buffered saline and stored for 12 weeks in various conditions (-20°C, 4°C, 20°C, and 37°C in dark, and 4°C and 20°C under ambient light). During storage, a very low amount of prematurely released drug molecules were detected (maximum of 7.5% for ApoDox prepared in PBS and 4.4% for ApoDox prepared in water). Fourier-transform infrared spectra revealed no significant differences in any of the samples after storage. Most of the ApoDox prepared in phosphate-buffered saline and ApoDox prepared in water and stored at -20°C formed very large aggregates (up to 487% of original size). Only ApoDox prepared in water and stored at 4°C showed no significant increase in size or shape. Although this storage caused slower internalization to LNCaP prostate cancer cells, ApoDox (2.5 µM of Dox) still retained its ability to inhibit completely the growth of 1.5×104 LNCaP cells after 72 hours. ApoDox stored at 20°C and 37°C in water was not able to deliver Dox inside the nucleus, and thus did not inhibit the growth of the LNCaP cells. Overall, our study demonstrates that ApoDox has very good stability over the course of 12 weeks when stored properly (at 4°C), and is thus suitable for use as a nanocarrier in the specific delivery of anticancer drugs to patients. Keywords: anticancer therapy, doxorubicin-loaded apoferritin, encapsulation, long-term stability, protein nanocarriersDostalova SVasickova KHynek DKrizkova SRichtera LVaculovicova MEckschlager TStiborova MHeger ZAdam VDove Medical Pressarticleanticancer therapydoxorubicin-loaded apoferritinencapsulationlong-term stabilityprotein nanocarriersMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2265-2278 (2017)
institution DOAJ
collection DOAJ
language EN
topic anticancer therapy
doxorubicin-loaded apoferritin
encapsulation
long-term stability
protein nanocarriers
Medicine (General)
R5-920
spellingShingle anticancer therapy
doxorubicin-loaded apoferritin
encapsulation
long-term stability
protein nanocarriers
Medicine (General)
R5-920
Dostalova S
Vasickova K
Hynek D
Krizkova S
Richtera L
Vaculovicova M
Eckschlager T
Stiborova M
Heger Z
Adam V
Apoferritin as an ubiquitous nanocarrier with excellent shelf life
description Simona Dostalova,1,2 Katerina Vasickova,1 David Hynek,1,2 Sona Krizkova,1,2 Lukas Richtera,1,2 Marketa Vaculovicova,1,2 Tomas Eckschlager,3 Marie Stiborova,4 Zbynek Heger,1,2 Vojtech Adam1,2 1Department of Chemistry and Biochemistry, Mendel University in Brno, 2Central European Institute of Technology, Brno University of Technology, Brno, 3Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, University Hospital Motol, Charles University, 4Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic Abstract: Due to many adverse effects of conventional chemotherapy, novel methods of targeting drugs to cancer cells are being investigated. Nanosize carriers are a suitable platform for this specific delivery. Herein, we evaluated the long-term stability of the naturally found protein nanocarrier apoferritin (Apo) with encapsulated doxorubicin (Dox). The encapsulation was performed using Apo’s ability to disassemble reversibly into its subunits at low pH (2.7) and reassemble in neutral pH (7.2), physically entrapping drug molecules in its cavity (creating ApoDox). In this study, ApoDox was prepared in water and phosphate-buffered saline and stored for 12 weeks in various conditions (-20°C, 4°C, 20°C, and 37°C in dark, and 4°C and 20°C under ambient light). During storage, a very low amount of prematurely released drug molecules were detected (maximum of 7.5% for ApoDox prepared in PBS and 4.4% for ApoDox prepared in water). Fourier-transform infrared spectra revealed no significant differences in any of the samples after storage. Most of the ApoDox prepared in phosphate-buffered saline and ApoDox prepared in water and stored at -20°C formed very large aggregates (up to 487% of original size). Only ApoDox prepared in water and stored at 4°C showed no significant increase in size or shape. Although this storage caused slower internalization to LNCaP prostate cancer cells, ApoDox (2.5 µM of Dox) still retained its ability to inhibit completely the growth of 1.5×104 LNCaP cells after 72 hours. ApoDox stored at 20°C and 37°C in water was not able to deliver Dox inside the nucleus, and thus did not inhibit the growth of the LNCaP cells. Overall, our study demonstrates that ApoDox has very good stability over the course of 12 weeks when stored properly (at 4°C), and is thus suitable for use as a nanocarrier in the specific delivery of anticancer drugs to patients. Keywords: anticancer therapy, doxorubicin-loaded apoferritin, encapsulation, long-term stability, protein nanocarriers
format article
author Dostalova S
Vasickova K
Hynek D
Krizkova S
Richtera L
Vaculovicova M
Eckschlager T
Stiborova M
Heger Z
Adam V
author_facet Dostalova S
Vasickova K
Hynek D
Krizkova S
Richtera L
Vaculovicova M
Eckschlager T
Stiborova M
Heger Z
Adam V
author_sort Dostalova S
title Apoferritin as an ubiquitous nanocarrier with excellent shelf life
title_short Apoferritin as an ubiquitous nanocarrier with excellent shelf life
title_full Apoferritin as an ubiquitous nanocarrier with excellent shelf life
title_fullStr Apoferritin as an ubiquitous nanocarrier with excellent shelf life
title_full_unstemmed Apoferritin as an ubiquitous nanocarrier with excellent shelf life
title_sort apoferritin as an ubiquitous nanocarrier with excellent shelf life
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/298a996171f54374a6ce7ba35af2119b
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AT vasickovak apoferritinasanubiquitousnanocarrierwithexcellentshelflife
AT hynekd apoferritinasanubiquitousnanocarrierwithexcellentshelflife
AT krizkovas apoferritinasanubiquitousnanocarrierwithexcellentshelflife
AT richteral apoferritinasanubiquitousnanocarrierwithexcellentshelflife
AT vaculovicovam apoferritinasanubiquitousnanocarrierwithexcellentshelflife
AT eckschlagert apoferritinasanubiquitousnanocarrierwithexcellentshelflife
AT stiborovam apoferritinasanubiquitousnanocarrierwithexcellentshelflife
AT hegerz apoferritinasanubiquitousnanocarrierwithexcellentshelflife
AT adamv apoferritinasanubiquitousnanocarrierwithexcellentshelflife
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