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

ABSTRACT

Chemotherapy is the most widely used treatment for cancer therapy, but its efficacy is limited by the side effects of non-specificcytotoxic drugs. Ligand-based targeting drug-delivery system is a solution to circumvent this issue. In this study, an ABCG2aptamer–doxorubicin complex was prepared, and its efficacy in targeted drug delivery to mitoxantrone-resistance breast cancer cellline (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 theMTT assay, and IC50 values were obtained. Cellular uptake of aptamer–doxorubicin complex was assessed by flow cytometrycellular uptake assay. Results: Fluorometric analysis of aptamer–doxorubicin showed 1–1.5 molar ratio of the drug to the aptamercould efficiently quench Dox fluorescence. MTTassay results showed that MCF7/MX cells were more resistant to doxorubicin thanMCF7 cells (IC50 3.172 ± 0.536 and 1.456 ± 0.154 lM, respectively). Flow cytometry and MTT assay results showed that theaptamer–doxorubicin complex could increase the uptake and cytotoxicity of doxorubicin in MCF7/MX cell line in comparison withfree doxorubicin, while the same treatments had no effect on IC50 of Dox on MCF7 cells. The results proposed that the ABCG2aptamer–drug complex can be effectively used for specific drug delivery to ABCG2-overexpressing cells.