Apoferritin as a ubiquitous nanocarrier with excellent shelf life
| Autor: | Marie Stiborová, Vojtech Adam, Zbynek Heger, Tomas Eckschlager, Lukas Richtera, Marketa Vaculovicova, Sona Krizkova, Simona Dostalova, David Hynek, Katerina Vasickova |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Drug
Male Materials science media_common.quotation_subject Biophysics Pharmaceutical Science Bioengineering Antineoplastic Agents 02 engineering and technology Pharmacology Shelf life Biomaterials 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Drug Stability International Journal of Nanomedicine Cell Line Tumor Drug Discovery LNCaP medicine Humans Doxorubicin anticancer therapy Neutral ph Internalization media_common Original Research Drug Carriers doxorubicin-loaded apoferritin Organic Chemistry Prostatic Neoplasms Water long-term stability General Medicine Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Drug Liberation protein nanocarriers 030220 oncology & carcinogenesis Cancer cell Apoferritins encapsulation Nanocarriers Drug Screening Assays Antitumor 0210 nano-technology medicine.drug |
| Zdroj: | International Journal of Nanomedicine. 2017, vol. 12, issue 1, p. 2265-2278. International Journal of Nanomedicine |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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