Multifunctional magnetic Fe₃O₄ nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance

Abstract

Background

Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe₃O₄ magnetic nanoparticles (Fe₃O₄-MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia.

Methods

Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe₃O₄-MNP, and Fe₃O₄-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe₃O₄-MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance.

Results

Fe₃O₄-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe₃O₄-MNP and Fe₃O₄-MNP-DNR-5-BrTet groups, especially in the Fe₃O₄-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe₃O₄-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression.

Conclusion

Fe₃O₄-MNP-DNR-5-BrTet with hyperthermia may be a potential approach for reversal of multidrug resistance in the treatment of leukemia.

Keywords:

• magnetic nanoparticles
• daunorubicin
• 5-bromotetrandrine
• multidrug resistance
• hyperthermia

Acknowledgment

This work was supported by the 973 National Nature Science Foundation of People’s Republic of China (2010CB732404), the National Nature Science Project of the People’s Republic of China (81170492), and the Key Subject Foundation of Jiangsu Province.

Disclosure

The authors report no conflicts of interests in this work.