title: Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance.
abstract: BACKGROUND
  Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe(3)O(4) magnetic nanoparticles (Fe(3)O(4)-MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia.
  
  
  METHODS
  Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe(3)O(4)-MNP, and Fe(3)O(4)-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe(3)O(4)-MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance.
  
  
  RESULTS
  Fe(3)O(4)-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe(3)O(4)-MNP and Fe(3)O(4)-MNP-DNR-5-BrTet groups, especially in the Fe(3)O(4)-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression.
  
  
  CONCLUSIONS
  Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia may be a potential approach for reversal of multidrug resistance in the treatment of leukemia.
authors.affiliation: Department of Hematology and Oncology, Key Medical Discipline, Jiangsu Province, Zhongda Hospital, and Faculty of Oncology, Medical School, Nanjing, People’s Republic of China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ren
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Cai
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Guohua
authors.initials: G
authors.lastname: Xia
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Jiahua
authors.initials: J
authors.lastname: Ding
authors.forename: Chong
authors.initials: C
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Bao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Tian
authors.forename: Huihui
authors.initials: H
authors.lastname: Song
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D044182:Benzylisoquinolines / Q000008:administration & dosage; D053148:Caspase 3 / Q000378:metabolism; D003131:Combined Modality Therapy; D003630:Daunorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006979:Hyperthermia, Induced; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D055909:Magnetic Field Therapy; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050997:Nanomedicine; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D058185:Magnetite Nanoparticles; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C514835:bromotetrandrine; D053148:Caspase 3; D003630:Daunorubicin