title: A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin.
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.
authors: Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China.
authors: Jian
authors: J
authors: Cheng
authors: Jun
authors: J
authors: Wang
authors: Baoan
authors: B
authors: Chen
authors: Guohua
authors: G
authors: Xia
authors: Xiaohui
authors: X
authors: Cai
authors: Ran
authors: R
authors: Liu
authors: Yanyan
authors: Y
authors: Ren
authors: Wen
authors: W
authors: Bao
authors: Xuemei
authors: X
authors: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000704:Analysis of Variance; D044182:Benzylisoquinolines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D003630:Daunorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008856:Microscopy, Fluorescence
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044182:Benzylisoquinolines; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; C514835:bromotetrandrine; D003630:Daunorubicin