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Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (4): 255-264.DOI: 10.5246/jcps.2017.04.026

• Original articles • Previous Articles     Next Articles

A novel type of functional epirubicin liposomes modified with DSPE-PEG2000-cyclopamine conjugate for eliminating heterogeneous breast cancer cells

Yingjie Hu, Jingying Zhang, Lei Liu, Yan Yan, Limin Mu, Jing Bai, Jiashuan Wu, Wanliang Lu*   

  1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2017-03-07 Revised:2017-03-21 Online:2017-04-26 Published:2017-04-15
  • Contact: Tel.: +86-010-82802683, E-mail: luwl@bjmu.edu.cn
  • Supported by:

    National Basic Research Program of China (973 Program, Grant No. 2013CB932501) and the National Science Foundation of China (Grant No. 81373343, 81673367).

Abstract:

Common chemotherapy is unable to eliminate the heterogeneous side population of cancer cells (such as cancer stem-likecells), resulting in poor prognosis. The heterogeneity of cancer cells causes an extensive multidrug resistance through the aberrantly active Hedgehog (Hh) signaling pathway. Cyclopamine is a chemical compound that can block Hh signaling pathway, and a combination use of cyclopamine with anticancer drug would be beneficial for killing heterogeneous cancer cells. In the present study, we aimed to develop a kind type of functional drug liposomes for eliminating heterogeneous cancer. The study was performed on human breast cancer cells. A distearoylphosphoethanolamine polyethylene glycol (DSPE-PEG2000)-cyclopamine conjugate was newly synthesized by a nucleophilic substitution reaction, and confirmed by MALDI-TOF mass. An HPLC method was established and validated for qualification of epirubicin. Functional epirubicin liposomes were successful constructed by modifyingwith DSPE-PEG2000-cyclopamine, displaying a particle size in nano-scale (approximately 98 nm) and a high epirubicin encapsulation (>97%). The CD44+/CD24-side population was characterized in defining heterogeneous breast cancer cells. As compared with regular epirubicin liposomes, functional epirubicin liposomes exhibited an evidently enhanced cellular drug uptake and a significant killing effect in overall breast cancer cells. In conclusion, the functional epirubicin liposomes could be a useful drug delivery carrier for eliminating heterogeneous breast cancer cells.

Key words: Cyclopamine conjugate, Epirubin, Liposomes, Heterogeneity, Breast cancer

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