Reversal in multidrug resistance by magnetic nanoparticle of Fe₃O₄ loaded with adriamycin and tetrandrine in K562/A02 leukemic cells

Original Research

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Authors: Baoan Chen, Qian Sun, Xuemei Wang, Feng Gao, Yongyuan Dai, et al

Published Date June 2008 Volume 2008:3(2) Pages 277 - 286

DOI: http://dx.doi.org/10.2147/IJN.S2714

Baoan Chen^1,5, Qian Sun^1,5, Xuemei Wang², Feng Gao¹, Yongyuan Dai¹, Yan Yin¹, Jiahua Ding¹, Chong Gao¹, Jian Cheng¹, Jingyuan Li², Xinchen Sun¹, Ningna Chen¹, Wenlin Xu³, Huiling Shen³, Delong Liu⁴

¹Department of Hematology, Zhongda Hospital, Southeast University, Nanjing, China; ²State Key Lab of Bioelectronics(Chien-Shiung Wu Laboratory), Southeast University, Nanjing 210096, China; ³Department of Hematology, The First People’s Hospital of Zhenjiang, Zhenjiang, China; ⁴Westchester Medical Center, New York Medical College, NY, USA; ⁵These authors have contributed equally to this work.

Abstract: Drug resistance is a primary hindrance for efficiency of chemotherapy. To investigate whether Fe₃O₄-magnetic nanoparticles (Fe₃O₄-MNPs) loaded with adriamycin (ADM) and tetrandrine (Tet) would play a synergetic reverse role in multidrug resistant cell, we prepared the drug-loaded nanoparticles by mechanical absorption polymerization to act with K562 and one of its resistant cell line K562/A02. The survival of cells which were cultured with these conjugates for 48 h was observed by MTT assay. Using cells under the same condition described before, we took use of fluorescence microscope to measure fluorescence intensity of intracellular ADM at an excitation wavelength of 488 nm. P-glycoprotein (P-gp) was analyzed with flow cytometer. The expression of mdr1 mRNA was measured by RT-PCR. The results showed that the growth inhibition efficacy of both the two cells increased with augmenting concentrations of Fe₃O₄-MNPs which were loaded with drugs. No linear correlation was found between fluorescence intensity of intracellular adriamycin and augmenting concentration of Fe₃O₄-MNPs. Tet could downregulate the level of mdr-1 gene and decrease the expression of P-gp. Furthermore, Tet polymerized with Fe₃O₄-MNPs reinforced this downregulation, causing a 100-fold more decrease in mdr1 mRNA level, but did not reduce total P-gp content. Our results suggest that Fe₃O₄-MNPs loaded with ADM or Tet can enhance the effective accumulation of the drugs in K562/A02. We propose that Fe₃O₄-MNPs loaded with ADM and Tet probably have synergetic effect on reversal in multidrug resistance.

Keywords: magnetic nanoparticles, tetrandrine, adriamycin, multidrug resistance reversal, leukemia K562/A02