title: Enhancing the anti-multiple myeloma efficiency in a cancer stem cell xenograft model by conjugating the ABCG2 antibody with microbubbles for a targeted delivery of ultrasound mediated epirubicin.
abstract: Although multiple myeloma (MM) treatment has improved in the last decade, it remains largely incurable. One of main reasons is that there are cancer stem cells (CSCs) in MM, which are responsible for MM's drug resistance and relapse. In this study, we used the targeting microbubbles (MBs) conjugated with anti-ABCG2 monoclonal antibody (mAb) for ultrasound mediated epirubicin (EPI) delivery to evaluate the therapeutic effectiveness of the novel agent in MM CSC xenograft model.
  
  
  
  MM CSCs, marked by CD138-CD34-cell phenotypes were isolated from human MM RPMI8226 cell line using immune magnetic activated cell sorting system, and inoculated into nonobese diabetic/severe combined immunodeficient mice by subcutaneous or intravenous injection. After the mice developed MM, they were intravenous injection treated with EPI, EPI-MBs+mAb, and EPI-MBs+mAb with ultrasound exposure, respectively.
  
  
  
  All treated mice showed inhibited tumor sizes or bone lesions, decreased renal damages and anemia, and increased MM bearing mice' survival. In particular, the EPI-MBs+mAb plus ultrasound exhibited significantly enhanced therapeutic MM effectiveness by inducing apoptosis compared with other biologic agents.
  
  
  
  The data provide evidence that EPI-MBs+mAb with ultrasound exposure might be available for treatment MM patients in clinic.
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China; Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Wu
authors.affiliation: School of Biological Science and Technology, Southeast University, Nanjing 210096, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Di
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Fengshu
authors.initials: F
authors.lastname: Zhao
authors.affiliation: School of Biological Science and Technology, Southeast University, Nanjing 210096, China.
authors.forename: Shouhua
authors.initials: S
authors.lastname: Luo
authors.affiliation: School of Biological Science and Technology, Southeast University, Nanjing 210096, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China. Electronic address: njdoujun@seu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000276:immunology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000276:immunology; D015251:Epirubicin / Q000008:administration & dosage*; D018796:Immunoconjugates / Q000008:administration & dosage; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C501412:Abcg2 protein, mouse; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D015251:Epirubicin
keywords: ATP-binding cassette sub-family G member 2; Cancer stem cells; Epirubicin; Microbubble; Multiple myeloma; Ultrasound