Effect of magnetic nanoparticles of Fe₃O₄ and wogonin on the reversal of multidrug resistance in K562/A02 cell line

Abstract

Background

Multidrug resistance is the main obstacle to the efficiency of systemic chemotherapy against hematologic malignancy. This study investigated the reversible effect of the copolymer wogonin and daunorubicin coloaded into Fe₃O₄ magnetic nanoparticles, and the mechanism potentially involved.

Methods

The growth inhibition rate of K562/A02 cells was investigated by MTT assay, and apoptosis of cells and the intracellular daunorubicin concentration were detected by flow cytometry. Distribution of nanoparticles taken up by K562/A02 cells was observed under a transmission electron microscope and demonstrated by Prussian blue staining. The transcription level of MDR1 mRNA and expression of P-glycoprotein were determined by reverse transcriptase polymerase chain reaction and Western blotting assay, respectively.

Results

The reversible effect of daunorubicin-wogonin magnetic nanoparticles was 8.87-fold that of daunorubicin + wogonin and of daunorubicin magnetic nanoparticles. Transmission electron microscopy and Prussian blue staining revealed that the nanoparticles were located in the endosome vesicles of cytoplasm. Also, the apoptosis rate and accumulation of intracellular daunorubicin in the daunorubicin-wogonin magnetic nanoparticle group were significantly higher than that in the daunorubicin, daunorubicin + wogonin, and daunorubicin magnetic nanoparticle groups. Furthermore, transcription of MDR1 mRNA and expression of P-glycoprotein in K562/A02 cells were significantly downregulated in the daunorubicin-wogonin magnetic nanoparticle group compared with the other groups.

Conclusion

These findings suggest that the remarkable effects of the novel daunorubicin-wogonin magnetic nanoparticle formulation on multidrug resistant K562/A02 leukemia cells would be a promising strategy for overcoming multidrug resistance.

Keywords:

• magnetic nanoparticles
• Fe₃O₄
• wogonin
• multidrug resistance
• daunorubicin
• P-glycoprotein

Acknowledgments

This work was supported financially by the National Key Basic Research Program 973 of China (2010CB732404), National Natural Science Funds of People’s Republic of China (81170492), and Key Medical Disciplines of Jiangsu Province.

Disclosure

The authors report no conflicts of interest in this work.