A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin
Jian Cheng1*, Jun Wang2*, Baoan Chen1, Guohua Xia1, Xiaohui Cai1, Ran Liu1, Yanyan Ren1, Wen Bao1, Xuemei Wang31Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China; 2Department of Hematology and Oncology, Nanjing Children&...
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Dove Medical Press
2011
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oai:doaj.org-article:823bcfb2fb884f42b17caaf73a9b80752021-12-02T04:59:16ZA promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin1176-91141178-2013https://doaj.org/article/823bcfb2fb884f42b17caaf73a9b80752011-09-01T00:00:00Zhttp://www.dovepress.com/a-promising-strategy-for-overcoming-mdr-in-tumor-by-magnetic-iron-oxid-a8372https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Jian Cheng1*, Jun Wang2*, Baoan Chen1, Guohua Xia1, Xiaohui Cai1, Ran Liu1, Yanyan Ren1, Wen Bao1, Xuemei Wang31Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China; 2Department of Hematology and Oncology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, People's Republic of China; 3National Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People's Republic of China *These authors have contributed equally to this work Abstract: To overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from multidrug resistance (MDR) and minimize adverse effects of chemotherapy agents, a novel chemotherapy formulation of magnetic nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin (DNR/BrTet-MNPs) was developed, and its effect on MDR leukemic cells was explored. After the DNR and Br were co-loaded onto a pluronic-stabilized and oleic acid-modified magnetic nanosystem, the physical characteristic and drug-loading capacity were evaluated. The cell toxicity of the self-prepared DNR/BrTet-MNPs formulation was then determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay; the cellular uptake of drug was demonstrated by fluorescent microscope. Lastly, the transcription of mdr1 and the expression of P-glycoprotein (P-gp) were detected by the reverse transcription reaction and western blotting assay, respectively. The results showed that the self-prepared DNR/BrTet-MNPs formulation possessed a sustained release of drug and displayed a dose-dependent antiproliferative activity on MDR leukemia K562/A02 cells. It also enhanced the accumulation of intracellular DNR in K562/A02 cells and downregulated the transcription of the mdr1 gene and the expression of P-gp. These findings suggest that the remarkable effect of the novel DNR/BrTet-MNPs formulation, acting as a drug depot system for the sustained release of the loaded DNR and BrTet, on multidrug resistance leukemia K562/A02 cells would be a promising strategy for overcoming MDR. Keywords: multidrug resistance, targeting drug delivery system, leukemiaWang XMBao WRen YYLiu RCai XHXia GHChen BAWang JCheng JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2123-2131 (2011) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Wang XM Bao W Ren YY Liu R Cai XH Xia GH Chen BA Wang J Cheng J A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
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Jian Cheng1*, Jun Wang2*, Baoan Chen1, Guohua Xia1, Xiaohui Cai1, Ran Liu1, Yanyan Ren1, Wen Bao1, Xuemei Wang31Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China; 2Department of Hematology and Oncology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, People's Republic of China; 3National Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People's Republic of China *These authors have contributed equally to this work Abstract: To overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from multidrug resistance (MDR) and minimize adverse effects of chemotherapy agents, a novel chemotherapy formulation of magnetic nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin (DNR/BrTet-MNPs) was developed, and its effect on MDR leukemic cells was explored. After the DNR and Br were co-loaded onto a pluronic-stabilized and oleic acid-modified magnetic nanosystem, the physical characteristic and drug-loading capacity were evaluated. The cell toxicity of the self-prepared DNR/BrTet-MNPs formulation was then determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay; the cellular uptake of drug was demonstrated by fluorescent microscope. Lastly, the transcription of mdr1 and the expression of P-glycoprotein (P-gp) were detected by the reverse transcription reaction and western blotting assay, respectively. The results showed that the self-prepared DNR/BrTet-MNPs formulation possessed a sustained release of drug and displayed a dose-dependent antiproliferative activity on MDR leukemia K562/A02 cells. It also enhanced the accumulation of intracellular DNR in K562/A02 cells and downregulated the transcription of the mdr1 gene and the expression of P-gp. These findings suggest that the remarkable effect of the novel DNR/BrTet-MNPs formulation, acting as a drug depot system for the sustained release of the loaded DNR and BrTet, on multidrug resistance leukemia K562/A02 cells would be a promising strategy for overcoming MDR. Keywords: multidrug resistance, targeting drug delivery system, leukemia |
| format |
article |
| author |
Wang XM Bao W Ren YY Liu R Cai XH Xia GH Chen BA Wang J Cheng J |
| author_facet |
Wang XM Bao W Ren YY Liu R Cai XH Xia GH Chen BA Wang J Cheng J |
| author_sort |
Wang XM |
| title |
A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_short |
A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_full |
A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_fullStr |
A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_full_unstemmed |
A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_sort |
promising strategy for overcoming mdr in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| publisher |
Dove Medical Press |
| publishDate |
2011 |
| url |
https://doaj.org/article/823bcfb2fb884f42b17caaf73a9b8075 |
| work_keys_str_mv |
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