Dear Editor,Among the large number of Veratrum steroid alkaloids(Zhang et al.,2020),cyclopamine has been shown to have various inhibitory mechanisms against cancer,including inhibition of the hedgehog signaling pathwa...Dear Editor,Among the large number of Veratrum steroid alkaloids(Zhang et al.,2020),cyclopamine has been shown to have various inhibitory mechanisms against cancer,including inhibition of the hedgehog signaling pathway,improvement of tumor tissue microenvironment,inhibition of cell respiration,promotion of cell apoptosis,and reversal of tumor drug resistance(Liu et al.,2023).The biosynthetic pathway of verazine,a possible metabolic precursor of cyclopamine,has been discovered in Veratrum californicum(Augustin et al.,2015).However,the content of Veratrum steroid alkaloids in plants is very low(Supplemental Figure 2),so reliance on direct extraction from plants for commercial production is not feasible.A more effective strategy is to synthesize rare plant secondary metabolites using synthetic biology technology(Liu et al.,2022).展开更多
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 multi...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.展开更多
基金supported by the National Key Research and Development Program of China(2023YFA0915800)the Jilin Provincial Agricultural Science&Technology Innovation Project(CXGC202105GH).
文摘Dear Editor,Among the large number of Veratrum steroid alkaloids(Zhang et al.,2020),cyclopamine has been shown to have various inhibitory mechanisms against cancer,including inhibition of the hedgehog signaling pathway,improvement of tumor tissue microenvironment,inhibition of cell respiration,promotion of cell apoptosis,and reversal of tumor drug resistance(Liu et al.,2023).The biosynthetic pathway of verazine,a possible metabolic precursor of cyclopamine,has been discovered in Veratrum californicum(Augustin et al.,2015).However,the content of Veratrum steroid alkaloids in plants is very low(Supplemental Figure 2),so reliance on direct extraction from plants for commercial production is not feasible.A more effective strategy is to synthesize rare plant secondary metabolites using synthetic biology technology(Liu et al.,2022).
基金National Basic Research Program of China(973 Program,Grant No.2013CB932501)the National Science Foundation of China(Grant No.81373343,81673367)
文摘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.
