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ABCG2 aptamer selectively delivers doxorubicin to drug-resistant breast cancer cells

  • Shirin Hashemitabar
  • Rezvan Yazdian-Robati
  • Maryam Hashemi
  • Mohammad Ramezani
  • Khalil AbnousEmail author
  • Fatemeh KalaliniaEmail author
Article
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Abstract

Chemotherapy is the most widely used treatment for cancer therapy, but its efficacy is limited by the side effects of non-specific cytotoxic drugs. Ligand-based targeting drug-delivery system is a solution to circumvent this issue. In this study, an ABCG2 aptamer–doxorubicin complex was prepared, and its efficacy in targeted drug delivery to mitoxantrone-resistance breast cancer cell line (MCF7/MX) was evaluated. The formation of aptamer–doxorubicin physical complex was analyzed by fluorometric analysis. The cytotoxicities of doxorubicin and aptamer–doxorubicin complex on MCF7 and MCF7/MX cell lines were evaluated by the MTT assay, and IC50 values were obtained. Cellular uptake of aptamer–doxorubicin complex was assessed by flow cytometry cellular uptake assay. Results: Fluorometric analysis of aptamer–doxorubicin showed 1–1.5 molar ratio of the drug to the aptamer could efficiently quench Dox fluorescence. MTT assay results showed that MCF7/MX cells were more resistant to doxorubicin than MCF7 cells (IC50 : 3.172 ± 0.536 and 1.456 ± 0.154 μM, respectively). Flow cytometry and MTT assay results showed that the aptamer–doxorubicin complex could increase the uptake and cytotoxicity of doxorubicin in MCF7/MX cell line in comparison with free doxorubicin, while the same treatments had no effect on IC50 of Dox on MCF7 cells. The results proposed that the ABCG2 aptamer–drug complex can be effectively used for specific drug delivery to ABCG2-overexpressing cells.

Keywords

ABCG2 aptamer breast cancer doxorubicin MDR 

Abbreviations

ABCG2

ATP-Binding Cassette sub-family G member 2

APT

Aptamer

DMSO

Dimethyl sulfoxide

DOX

Doxorubicin

FBS

Fetal bovine serum

IC50

Inhibitory concentration 50%

MDR

Multi-drug resistance

MFI

Mean fluorescence intensity

MX

Mitoxantrone

PBS

Phosphate-buffered saline

SELEX

Systematic evolution of ligands by exponential enrichment

Notes

Acknowledgements

The research presented in this paper was part of a Pharm.D thesis of Shirin Hashemitabar. The authors are indebted to the Research Council of Mashhad University of Medical Sciences, Iran, for approval and financial support of this project (Grant No. 940164).

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Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  • Shirin Hashemitabar
    • 1
  • Rezvan Yazdian-Robati
    • 2
  • Maryam Hashemi
    • 3
  • Mohammad Ramezani
    • 3
    • 4
  • Khalil Abnous
    • 4
    • 5
    Email author
  • Fatemeh Kalalinia
    • 1
    • 6
    Email author
  1. 1.Biotechnology Research Center, Institute of Pharmaceutical TechnologyMashhad University of Medical SciencesMashhadIran
  2. 2.Molecular and Cell biology Research Center, Faculty of MedicineMazandaran University of Medical SciencesSariIran
  3. 3.Nanotechnology Research Center, Institute of Pharmaceutical TechnologyMashhad University of Medical SciencesMashhadIran
  4. 4.Pharmaceutical Research Center, Institute of Pharmaceutical TechnologyMashhad University of Medical SciencesMashhadIran
  5. 5.Medicinal Chemistry Department, Academy of PharmacyMashhad University of Medical SciencesMashhadIran
  6. 6.Genetic Research CenterMashhad University of Medical SciencesMashhadIran

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