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.
    International Journal of Nanomedicine 07/2013; 8:2567-73. DOI:10.2147/IJN.S43417 · 4.38 Impact Factor
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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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    ABSTRACT: The present study evaluated whether magnetic nanoparticles containing Fe(3)O(4) could enhance the activity of gambogic acid in human colon cancer cells, and explored the potential mechanisms involved. Cytotoxicity was evaluated by MTT assay. The percentage of cells undergoing apoptosis was analyzed by flow cytometry, and cell morphology was observed under both an optical microscope and a fluorescence microscope. Reverse transcriptase polymerase chain reaction and Western blot assay were performed to determine the transcription of genes and expression of proteins, respectively. Gambogic acid could inhibit proliferation of LOVO cells in a dose-dependent and time-dependent manner and induce apoptosis, which was dramatically enhanced by magnetic nanoparticles containing Fe(3)O(4). The typical morphological features of apoptosis in LOVO cells were observed after treatment comprising gambogic acid with and without magnetic nanoparticles containing Fe(3)O(4). Transcription of cytochrome c, caspase 9, and caspase 3 genes was higher in the group treated with magnetic nanoparticles containing Fe(3)O(4) and gambogic acid than in the groups that received gambogic acid or magnetic nanoparticles containing Fe(3)O(4), but transcription of phosphatidylinositol 3-kinase, Akt, and Bad genes decreased. Notably, expression of cytochrome c, caspase 9, and caspase 3 proteins in the group treated with gambogic acid and magnetic nanoparticles containing Fe(3)O(4) was higher than in the groups receiving magnetic nanoparticles containing Fe(3)O(4) or gambogic acid, while expression of p-PI3K, p-Akt, p-Bad, pro-caspase 9, and pro-caspase 3 degraded. Magnetic nanoparticles containing Fe(3)O(4) can enhance apoptosis induced by gambogic acid which may be closely related to regulation of the PI3K/Akt/Bad pathway in the treatment of human colon cancer.
    International Journal of Nanomedicine 07/2012; 7:4109-18. DOI:10.2147/IJN.S32475 · 4.38 Impact Factor
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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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    ABSTRACT: Amongst all leukemias, Bcr-Abl positive chronic myelogenous leukemia (CML) confers resistance to native drug due to multi drug resistance and also resistance to p53 and fas ligand pathways. In the present study, we have investigated the efficacy of microtubule stabilizing paclitaxel loaded magnetic nanoparticles (pac-MNPs) to ascertain its cytotoxic effect on Bcr-Abl positive K562 cells. For active targeted therapy, pac-MNPs were functionalized with lectin glycoprotein which resulted in higher cellular uptake and lower IC(50) value suggesting the efficacy of targeted delivery of paclitaxel. Both pac-MNPs and lectin conjugated pac-MNPs have a prolonged circulation time in serum suggesting increased bioavailability and therapeutics index of paclitaxel in vivo. Further, the molecular mechanism pertaining to pac-induced cytotoxicity was analyzed by studying the involvement of different apoptotic pathway proteins by immunoblotting and quantitative PCR. Our study revealed simultaneous activation of JNK pathway leading to Bcr-Abl instability and the extrinsic apoptotic pathway after pac-MNPs treatment in two Bcr-Abl positive cell lines. In addition, the MRI data suggested the potential application of MNPs as imaging agent. Thus our in vitro and in vivo results strongly suggested the pac-MNPs as a future prospective theranostic tool for leukemia therapy.
    PLoS ONE 11/2011; 6(11):e26803. DOI:10.1371/journal.pone.0026803 · 3.23 Impact Factor
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