Reversal of Multidrug Resistance by Magnetic Fe₃O₄ Nanoparticle Loading Daunorubicin and Bromotetrandrine in Nude Mice Bearing Leukemia Tumor Xenografts

This paper was to study the reverse effect of magnetic Fe₃O₄ nanoparticle loading daunorubicin and bromotetrandrine(Fe₃O₄-MNPs/DNR/BrTet) with the conduction of alternating magnetic field in nude mice bearing K562/A02 xenografts, and to provide theoretic evidence for the clinical application of malignancies as a new treatment.

20 BALB/c nude mice with equivalent different gender, which were age-matched (four weeks of age) and weight-matched (16-22g), were randomly divided to 5 groups. The subclone of K562/A02 cells was inoculated subcutaneously into the oxter of all athymic nude mice. Group 1 each mouse was given 0.9% normal saline 0.2ml/once; Group 2, DNR 1mg/kg and BrTet 1mg/kg; Group 3, DNR 1mg/ml and BrTet 10mg/kg; Group 4, Fe₃O₄-MNPs 10.5mg/kg; Group 5, Fe₃O₄-MNPs/DNR/BrTet 12.5mg/kg(DNR: BrTet: Fe₃O₄-MNPs=1:1:10.5). After being delivered in an alternating magnetic field for 40minutes, the incidence of growth characteristics of mice, and volume of tumor were observed for 14 days. At the 14th day, the mice were sacrificed by cervical dislocation to detect all tumors by weight measuring, Hematoxylin and eosin staining, Western-blot and so on.

The average tumors' weight and volume was much less in Group 4 and 5 than others, there were significantly different (P<0.05). The results of hematoxylin and eosin staining showed that obvious necrosis area was observed in Group 4 and Group 5, and there was less necrosis in the Group 3 compared with the other groups. The Western-blot showed the expression of caspase-3 and bax in Group 4 and 5 increased two times than other groups, while the expression of bcl-2 decreased to half of others.

Fe₃O₄-MNPs/DNR/BrTet can reverse multidrug resistance efficiently in vivo through inducing apoptosis, which may be related to the upregulating of bax and downregulating of bcl-2. Moreover, our synthesized magnetic Fe₃O₄ nanoparticle may be as a high efficiency and security medicine carriers to treat malignancies.

No relevant conflicts of interest to declare.