title: Target therapy of multiple myeloma by PTX-NPs and ABCG2 antibody in a mouse xenograft model.
abstract: Multiple myeloma (MM) remains to be an incurable disease. The purpose of this study was to evaluate the effect of ABCG2 monoclonal antibody (McAb) combined with paclitaxel (PTX) conjugated with Fe3O4 nanoparticles (NPs) on MM progressed from cancer stem cells (CSCs) in non-obese-diabetic/severe-combined-immunodeficiency (NOD/SCID) mouse model. Mice were injected with MM CSCs as marked by CD138-CD34- phenotypes through tail veins. The developed MM mice were examined by micro-computer tomography scanning, ultrasonography and enzyme-linked immunosorbent analysis. These mice were then intravenously treated with different combinations of NPs, PTX, McAb, PTX-NPs and melphalan/prednisone once a week for four weeks. The injected mice developed characteristic MM-associated syndromes, including lytic bone lesions, renal damages and proteinuria. All the treated mice showed decrease in bone lesions, renal damages and anemia but increase in apoptosis compared with the mice treated with NPs only. In particular, the treatment with ABCG2 McAb plus PTX-NPs induced the strongest therapeutic response and had an efficacy even better than that of melphalan/prednisone, a conventional regimen for MM patients. These data suggest that PTX-NPs with ABCG2 McAb can be developed into potential treatment regimens for patients with relapsed/refractory MM.
authors: Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210009, China.
authors: Cuiping
authors: C
authors: Yang
authors: School of Biological Science & Medical Engineering & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210096, China.
authors: Fei
authors: F
authors: Xiong
authors: Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210009, China.
authors: Jun
authors: J
authors: Dou
authors: Department of Hematology, Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Jun
authors: J
authors: Xue
authors: The Center for Vascular and Inflammatory Diseases, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Xi
authors: X
authors: Zhan
authors: Department of Oncology, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors: Fangfang
authors: F
authors: Shi
authors: Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210009, China.
authors: Miao
authors: M
authors: Li
authors: Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210009, China.
authors: Songyan
authors: S
authors: Wu
authors: School of Biological Science & Medical Engineering & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210096, China.
authors: Shouhua
authors: S
authors: Luo
authors: School of Biological Science & Medical Engineering & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210096, China.
authors: Tianzhu
authors: T
authors: Zhang
authors: School of Biological Science & Medical Engineering & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210096, China.
authors: Yu
authors: Y
authors: Zhang
authors: School of Biological Science & Medical Engineering & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210096, China.
authors: Ji
authors: J
authors: Ming
authors: School of Biological Science & Medical Engineering & Collaborative Innovation Center of Suzhou NanoScience and Technology, Southeast University, Nanjing 210096, China.
authors: Ning
authors: N
authors: Gu
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D001842:Bone and Bones / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008558:Melphalan / Q000008:administration & dosage; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology; D017239:Paclitaxel / Q000008:administration & dosage*; D010641:Phenotype; D011241:Prednisone / Q000008:administration & dosage; D053668:Syndecan-1 / Q000378:metabolism; D055114:X-Ray Microtomography; D023041:Xenograft Model Antitumor Assays
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D004337:Drug Carriers; C508600:IL6 protein, human; D015850:Interleukin-6; D009363:Neoplasm Proteins; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D017239:Paclitaxel; D008558:Melphalan; D011241:Prednisone
keywords: ATP-binding cassette sub-family G member 2; cancer stem cells; multiple myeloma; nanoparticles; paclitaxel