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
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  • Supported by:

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


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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