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

نویسندگان

  • Yanyan Ren
  • Haijun Zhang
  • Baoan Chen
  • Jian Cheng
  • Xiaohui Cai
  • Ran Liu
  • Guohua Xia
  • Weiwei Wu
  • Shuai Wang
  • Jiahua Ding
  • Chong Gao
  • Jun Wang
  • Wen Bao
  • Lei Wang
  • Liang Tian
  • Huihui Song
  • Xuemei Wang
چکیده

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 Fe(3)O(4) magnetic nanoparticles (Fe(3)O(4)-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, Fe(3)O(4)-MNP, and Fe(3)O(4)-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe(3)O(4)-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 Fe(3)O(4)-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe(3)O(4)-MNP and Fe(3)O(4)-MNP-DNR-5-BrTet groups, especially in the Fe(3)O(4)-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression. CONCLUSION Fe(3)O(4)-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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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2012