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

Yanyan Ren^1,2,*, Haijun Zhang^1,2,*, Baoan Chen¹, Jian Cheng¹, Xiaohui Cai¹, Ran Liu¹, Guohua Xia¹, Weiwei Wu¹, Shuai Wang¹, Jiahua Ding¹, Chong Gao¹, Jun Wang¹, Wen Bao¹, Lei Wang¹, Liang Tian¹, Huihui Song¹, Xuemei Wang<sup>1,2

1</sup>Department of Hematology and Oncology, Key Medical Discipline, Jiangsu Province, Zhongda Hospital, and Faculty of Oncology, Medical School, Nanjing, ²State Key Laboratory of Bioelectronics, Southeast University, Nanjing, People's Republic of China

*These authors contributed equally to this work

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

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