Volume 26, No 6, Jun 2016

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 26 Issue 6, June 2016: 713-727

ORIGINAL ARTICLES

Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles

Jingwei Ma^1,2,*, Yi Zhang^1,*, Ke Tang^1,2, Huafeng Zhang¹, Xiaonan Yin¹, Yong Li², Pingwei Xu³, Yanling Sun², Ruihua Ma², Tiantian Ji², Junwei Chen³, Shuang Zhang³, Tianzhen Zhang¹, Shunqun Luo², Yang Jin⁴, Xiuli Luo⁵, Chengyin Li⁵, Hongwei Gong⁵, Zhixiong Long⁶, Jinzhi Lu¹, Zhuowei Hu⁷, Xuetao Cao¹, Ning Wang^3,8, Xiangliang Yang⁹ and Bo Huang^1,2

¹National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China
²Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China
³Laboratory for Cell Biomechanics and Regenerative Medicine, Department of Biomedical Engineering, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
⁴Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
⁵Department of Oncology, Hubei Provincial Hospital of TCM, Wuhan, Hubei 430061, China
⁶Department of Oncology, the Fifth Hospital of Wuhan, Wuhan, Hubei 430050, China
⁷Molecular Immunology and Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
⁸Department of Mechanical Science and Engineering, College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
⁹National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China Correspondence: Bo Huang,(tjhuangbo@hotmail.com)

Developing novel approaches to reverse the drug resistance of tumor-repopulating cells (TRCs) or stem cell-like cancer cells is an urgent clinical need to improve outcomes of cancer patients. Here we show an innovative approach that reverses drug resistance of TRCs using tumor cell-derived microparticles (T-MPs) containing anti-tumor drugs. TRCs, by virtue of being more deformable than differentiated cancer cells, preferentially take up T-MPs that release anti-tumor drugs after entering cells, which in turn lead to death of TRCs. The underlying mechanisms include interfering with drug efflux and promoting nuclear entry of the drugs. Our findings demonstrate the importance of tumor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.

10.1038/cr.2016.53

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