Daunorubicin Loaded Magnetic Nanoparticles of Fe3O4 Greatly Enhance the Responses to Chemotherapy and Induce Apoptosis of Multidrug-Resistant K562 Cells in a Human-Nude Mice Xenograft Leukemia Model

Object: To the effect of Fe₃O₄-magnetic nanoparticle loaded with DNR on multidrugresistant K562 cells in vivo.

Methods: K562-n and its MDR counterpart K562-n/VCR cell were inoculated subcutaneously into both sides of the back of nude mice (5×10⁶ cells/each) to establish a human leukemia xenograft model. The mice were randomly divided into group A receiving normal saline every other day for 20days, group B receiving DNR every other day for 20days, group C receiving Fe₃O₄-magnetic nanoparticle every other day for 20days, group D receiving Fe₃O₄-magnetic nanoparticle loaded with DNR every other day for 20days, and group E receiving Fe₃O₄-magnetic nanoparticle containing DNR every other day for 20days with a magnetic field built on the surface of the tumor tissue. The tumor volume was measured on the day 1, 5, 9, 13, 17 and 21d after the first treatment. Tumor tissues were isolated for examination of the expression of mdr-1, bcl-2, bax and caspase-3 by reverse transcription polymerase chain reaction and Western blotting.

Results: For K562-n/VCR tumor, the tumor volume was markedly lower in groups D and E than in groups A, B and C (group D or E vs group A, B or C, P < 0.05). The transcription of mdr-1 and Bcl-2 gene was significantly lower in groups D and E than in groups A, B and C (group D or E vs group A, B or C, P < 0.05). So did the protein expression of Bcl-2. However, there were no differences among these groups about the protein expression of P-gp. The protein and mRNA expressions of Bax and Caspase-3 in groups D and E were increased significantly compared with groups A, B and C (group D or E vs group A, B or C, P < 0.05). The tumor volume of K562-n was markedly lower in groups C, D and E than in groups A and B (group C, D or E vs group A or B, P < 0.05).

Conclusion: In conclusion, DNR loaded Fe₃O₄-magnetic nanoparticles can suppress the growth and induce apoptosis further on the MDR K562-n/VCR tumor in vivo compared to DNR alone but not on the K562-n tumor. The external magnetic field failed to improve the antitumor effect.