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供职机构:北京大学医学部药学院天然药物及仿生药物国家重点实验室更多>>
发文基金:国家重点基础研究发展计划更多>>
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A novel type of functional epirubicin liposomes modified with DSPE-PEG_(2000)-cyclopamine conjugate for eliminating heterogeneous breast cancer cells
2017年
Common chemotherapy is unable to eliminate the heterogeneous side population of cancer cells (such as cancer stem-like cells), 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 fimctional 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 epimbicin liposomes were successful constructed by modifying with DSPE-PEG2o00-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, fimctional 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.
胡英杰张靖莹刘磊阎妍沐黎敏白婧吴佳栓吕万良
关键词:HETEROGENEITY
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