Research Article

Anti-ABCG2 monoclonal antibody in combination with paclitaxel nanoparticles against cancer stem-like cell activity in multiple myeloma

Department of Pathogenic Biology & Immunology, Medical School, Southeast University, Nanjing 210009, China

^‡Authors contributed equally

Jiangsu Laboratory for Biomaterials & Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China

^‡Authors contributed equally

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Jing Wang^‡

Department of Gynecology & Obstetrics, Zhongda Hospital, Southeast University, Nanjing 210009, China

^‡Authors contributed equally

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Jun Dou

* Author for correspondence

Department of Pathogenic Biology & Immunology, Medical School, Southeast University, Nanjing 210009, China.

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Email the corresponding author at njdoujun@yahoo.com.cn

Junsong Chen

Department of Pathogenic Biology & Immunology, Medical School, Southeast University, Nanjing 210009, China

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Dengyu Chen

Department of Pathogenic Biology & Immunology, Medical School, Southeast University, Nanjing 210009, China

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Yu Zhang

Jiangsu Laboratory for Biomaterials & Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China

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Shouhua Luo

Jiangsu Laboratory for Biomaterials & Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China

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Ning Gu

Jiangsu Laboratory for Biomaterials & Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China

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Published Online:19 Dec 2013https://doi.org/10.2217/nnm.12.216

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Abstract

Aim: To investigate the effects of anti-ABCG2 monoclonal antibodies (mAbs) in combination with paclitaxel iron oxide nanoparticles (PTX-NPs) on CD138^-CD34^- multiple myeloma (MM) cancer stem cells (CSCs) in JJN3 cells. Materials & methods: PTX-NPs were prepared using the hydrophobic interaction of the polyoxypropylene chain and oleic acid on the surface of iron oxide NPs and were targeted to the ABCG2 transporter overexpressing MM CSCs with mAbs. Results: The data showed that MM CSCs have strong drug resistance and tumorigenicity compared with non-MM CSCs. PTX-NPs combined with mAbs led to a significant reduction in the tumor volume, a visible alleviation of lytic bone lesions and a markedly increased survival rate in contrast to using a single agent in MM CSCs when it was transplanted to nonobese diabetic/severe combined immunodeficiency mice. Conclusion: This study is the first to report on the anti-MM CSC activity by PTX-NPs as a single agent or used together with anti-ABCG2 mAbs to treat MM. These findings provide a rationale for future clinical trials.

Original submitted 18 June 2012; Revised submitted 29 November 2012; Published online 27 March 2013

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Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Published online 19 December 2013

Published in print January 2014

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Acknowledgements

The authors thank Y Liu from the Medical School, Southeast University, Nanjing, China, for monitoring the tumor volume and weight, and they also thank G Dong from the School of Biological Science and Medical Engineering, Southeast University, for performing the microcomputed tomography detection.

Financial & competing interests disclosure

This work was supported by the 973 National Nature Science Foundation of the People’s Republic of China (2011CB933500) and Graduate Student Research and Innovation Program of Jiangsu Province (CXZZ_0174) and the Scientific Research Foundation of Graduate School of Southeast University (YBJJ1222) as well as the National Natural Science Foundation of China (No. 81001412, 61127002 and 61179035). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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