Targeted delivery of epirubicin to breast cancer cells using poly-aptamer DNA nanocarriers prepared by the RCA method with multiple repeats of aptamers of FOXM1 and AS1411

Abstract

Objective We evaluated the DNA nanocarriers synthesized by rolling circle amplification (RCA), composed of multiple repeats of AS1411 and FOXM1 aptamers for targeted epirubicin delivery to breast cancer cells. Methods Agarose gel electrophoresis and scanning electron microscopy were used to nanostructure characterizing. Drug loading and drug release were determined by fluorometry. Cytotoxicity comparison by MTT assay was applied among epirubicin, nanoparticle, and complex (nanoparticle carrying epirubicin) in L929 (normal murine fibroblast) and 4T1 (murine mammary carcinoma) cells. Cellular epirubicin internalization was assessed by flow cytometry and fluorescence imaging. In vivo studies in 4T1 tumor-bearing BALB/c mice were conducted by monitoring tumor volume, mouse weight, and mortality rate and measuring the accumulated epirubicin in organs. Results The negatively charged nanoparticles were under 200 nm and stable. Fifty microliters of 6 μM epirubicin was loaded in 50 μL nanoparticle. Epirubicin release at acidic pH was more. Complex compared with epirubicin, had more entry and cytotoxicity in target cells (p value ≤.01), higher therapeutic effect (p value ≤.001), and tumor drug accumulation. Conclusion The poly-aptamer nanocarriers have the characteristics of being safe, stable, efficient epirubicin loading, pH-dependent drug release, and tumor-targeting ability in vitro and in vivo.