Daunorubicin-loaded magnetic nanoparticles of Fe3O4 overcome multidrug resistance and induce apoptosis of K562-n/VCR cells in vivo

Department of Hematology.
International Journal of Nanomedicine (Impact Factor: 4.38). 10/2009; 4:201-8.
Source: PubMed


Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy. We evaluated the effect of daunorubicin (DNR)-loaded magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) on K562-n/VCR cells in vivo. K562-n and its MDR counterpart K562-n/VCR cell were inoculated into nude mice subcutaneously. The mice were randomly divided into four groups: group A received normal saline, group B received DNR, group C received MNPs-Fe3O4, and group D received DNR-loaded MNPs-Fe3O4. For K562-n/VCR tumor, the weight was markedly lower in group D than that in groups A, B, and C. The transcriptions of Mdr-1 and Bcl-2 gene were significantly lower in group D than those in groups A, B, and C. The expression of Bcl-2 was lower in group D than those in groups A, B, and C, but there was no difference in the expression of P-glycoprotein. The transcriptions and expressions of Bax and caspase-3 in group D were increased significantly when compared with groups A, B, and C. In conclusion, DNR-loaded MNPs-Fe3O4 can overcome MDR in vivo.

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    • "Nanoparticles loaded with chemotherapeutic drugs have been used to successfully deliver drugs to the cytoplasm, nucleus, and other specific organelles.26–28 For example, DNR-loaded magnetic nanoparticles of Fe3O4 can overcome MDR.29 In another study, nickel nanoparticles have shown increased cancer cell membrane permeability.7 "
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    ABSTRACT: Recently nanoparticles have been extensively studied and have proven to be a promising candidate for cancer treatment and diagnosis. In the current study, we examined the chemo-sensitizing activity of a mixture of nanodiamond (ND) and nanoplatinum (NP) solution known as DPV576, against multidrug-resistant (MDR) human myeloid leukemia (HL60/AR) and MDR-sensitive cells (HL60). Cancer cells were cultured with different concentrations of daunorubicin (DNR) (1 × 10 (-9)-1 × 10 (-6) M) in the presence of selected concentrations of DPV576 (2.5%-10% v/v). Cancer cell survival was determined by MTT assay, drug accumulation by flow cytometry and confocal laser scanning microscopy (CLSM), and holes and structural changes by atomic force microscopy (AFM). Co-treatment of HL60/AR cells with DNR plus DPV576 resulted in the reduction of the IC50 to 1/4th. This was associated with increased incidences of holes inside the cells as compared with control untreated cells. On the other hand, HL60 cells did not show changes in their drug accumulation post-treatment with DPV576 and DNR. We conclude that DPV576 is an effective chemo-sensitizer as indicated by the reversal of HL60/AR cells to DNR and may represent a potential novel adjuvant for the treatment of chemo-resistant human myeloid leukemia.
    Full-text · Article · Jul 2013 · International Journal of Nanomedicine
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    • "Recently, magnetic nanoparticles containing Fe3O4, which have excellent biocompatibility10 and improved intracellular penetration,11,12 have become a focus for potential application in human medicine, including the delivery of anticancer drugs to overcome drug resistance and enhance the effectiveness of chemotherapy.12,13 Accumulating research has shown that not only can a combination of magnetic nanoparticles containing Fe3O4 and adriamycin have a significant cytotoxic effect on drug-resistant K562/A02 leukemia cells,14,15 but also that a combination of magnetic nanoparticles containing Fe3O4 and antitumor drugs may interact synergistically to induce apoptosis in cancer cells. "
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    • "The application of the magnetic nanoparticles (MNPs) in the field of biomedical application such as magnetic drug delivery, magnetic resonance imaging, transfection, cell and tissue targeting, has pooled considerable attention due to their intrinsic magnetic properties [15], [16], [17]. The MNPs mediated chemotherapeutics have revealed significant synergistic effect on the apoptosis of leukemic cells [18], [19], [20]. Chen et al. have studied the synergistic effect of gambosic acid and daunomycin on the drug accumulation and apoptosis of leukemia cells intervened by iron oxide (Fe3O4) nanoparticles [21]. "
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