Apoferritin-mediated doxorubicin internalization through transferrin receptor 1

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Date
2017-12-31
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Mark
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Mendel University in Brno
Abstract
This work is aimed at the possibilities of targeted drug delivery into the tumour tissue. This approach can greatly reduce the otherwise serious side effects of conventional treatment - systemic toxicity. For this purpose, ubiquitous protein cage apoferritin was employed as a carrier of cytotoxic drugs. Its molecule size of 10-12 nm allows it to employ the effect of increased permeability and retention as well as to avoid renal clearance. The cellular uptake of this carrier is known to be mediated via the transferrin receptor 1 (TfR1), which is overexpressed on metabolically highly active cells, such as cancer cells. Therefore, apoferritin's ability to deliver drug molecules to site-of-action was tested using cell lines with high, medium and low expression of TfR1. The optimal conditions for studying the expression of TfR1 using western blotting were as follows: lysate of 50,000 cells applied in non-reducing non-denaturing buffer and the concentration of the primary antibody of 1.0 µg/mL. The properties of encapsulated doxorubicin were not affected by apoferritin, thus preserving its toxicity for cells with high level of TfR1expression (30% growth inhibition of these cells after 24 h of treatment). The suitable usage of apoferritin as a nanocarrier for chemotherapeutic delivery was confirmed in this work.
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en
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(C) Mendel University in Brno
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