期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 7, 期 -, 页码 2261-2269出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S29357
关键词
magnetic nanoparticles; daunorubicin; 5-bromotetrandrine; multidrug resistance; hyperthermia
资金
- 973 National Nature Science Foundation of People's Republic of China [2010CB732404]
- National Nature Science Project of the People's Republic of China [81170492]
- Key Subject Foundation of Jiangsu Province
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.
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