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

Abstract

Drug resistance is a primary hindrance for effi ciency of chemotherapy. To investigate whether Fe 3 O 4 -magnetic nanoparticles (Fe 3 O 4 -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 fl uorescence microscope to measure fl uorescence intensity of intracellular ADM at an excitation wavelength of 488 nm. P-glycoprotein (P-gp) was analyzed with fl ow cytometer. The expression of mdr1 mRNA was measured by RT-PCR. The results showed that the growth inhibition effi cacy of both the two cells increased with augmenting concentrations of

Nanodrug delivery in reversing multidrug resistance in cancer cells

“…Co-administration of Doxorubicin and magnetite nanoparticles in presence of magnetic field showed cytotoxic effects against breast cancer cell lines MDA-MB-468 with greater than 80% cell death in hyperthermia combination than with Doxorubicin alone (Sadeghi-Aliabadi et al, 2013 ). Similar drug resistance inhibitory effect of magnetite nanoparticles loaded with Doxorubicin and Tetrandrine against K562 leukemia cells have been reported by Wang et al ( 2007 ), Chen et al ( 2008 ). Significant reduction in transcriptions of Mdr-1 and Bcl-2 gene and increased expressions of Bax and caspase-3 in K562-n and K562-n/VCR cells in-vivo in nude mice revealed the potential of Daunorubicin magnetic nanoparticles to overcome multi-drug resistance (Chen et al, 2009b ).…”

“…Cisplatin magnetic nanoparticles enhanced inhibition of A549 cells and cisplatin-resistant A549 cells in MDR lung cancer cells, lowered the levels of MRP1, lung resistance-related protein, Akt and Bad pathways and increased the levels of caspase-3 genes and proteins (Li et al, 2013a ). Single drug Tetrandrine loaded magnetic nanoparticles revealed a 100-fold lowering in mdrl mRNA level but no reduction in total P-gp content while magnetic nanoparticles loaded with Adriamycin and Tetrandrine synergistically reversed multidrug resistant in K562/A02 resistant cell lines (Chen et al, 2008 ). Heparin coated Doxorubicin super-paramagnetic iron oxide nanoparticles promoted apoptosis due to regulation of anti-apoptotic genes including caspase-3, bax, bcl-2 and surviving in human ovarian cancer cell lines A2780 (Javid et al, 2011 ).…”

An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles

“…Such limitations were addressed through the development of various targeted delivery systems involving the conjugation of drug to various biomaterials such as biodegradable polymers made up of polyethylenimine [4] , PLGA [5] , modified liposomes [6] – [9] , peptides and proteins [10] , [11] . Recent developments include introduction of nanoparticles consisting of poly (ethyl amine)-b-poly(n-isopropyl acetylated derivative), nanoparticles of Fe 3 O 4 [12] , [13] , polymeric dendrimers [14] , [15] , poly hydrogen acylated nanoparticles, core-shell co-polymer nanoparticles [16] – [18] , DOTA–NHS-ester [19] , PEG-PEL nanoparticles [20] . Though these materials are biocompatible, they lack target-specificity besides their high energy-demanding for degradation of biomaterial in cells and tissues.…”