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

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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.

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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

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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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Authors and Affiliations

  1. Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran

    Shirin Hashemitabar & Fatemeh Kalalinia

  2. Molecular and Cell biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Rezvan Yazdian-Robati

  3. Nanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran

    Maryam Hashemi & Mohammad Ramezani

  4. Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Ramezani & Khalil Abnous

  5. Medicinal Chemistry Department, Academy of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Khalil Abnous

  6. Genetic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Kalalinia

Authors
  1. Shirin Hashemitabar
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  2. Rezvan Yazdian-Robati
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  3. Maryam Hashemi
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  4. Mohammad Ramezani
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  5. Khalil Abnous
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  6. Fatemeh Kalalinia
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Corresponding authors

Correspondence to Khalil Abnous or Fatemeh Kalalinia.

Additional information

Communicated by Rita Mulherkar.

Corresponding editor: Rita Mulherkar

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Hashemitabar, S., Yazdian-Robati, R., Hashemi, M. et al. ABCG2 aptamer selectively delivers doxorubicin to drug-resistant breast cancer cells. J Biosci 44, 39 (2019). https://doi.org/10.1007/s12038-019-9854-x

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  • DOI: https://doi.org/10.1007/s12038-019-9854-x

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