A polymer-based nanocarrier was developed for the co-delivery of epigenetic and chemotherapeutic drugs. The sterically stabilized hybrid micelle system uses micelles composed of D-a-tocopheryl polyethylene glycol 1000...A polymer-based nanocarrier was developed for the co-delivery of epigenetic and chemotherapeutic drugs. The sterically stabilized hybrid micelle system uses micelles composed of D-a-tocopheryl polyethylene glycol 1000 succinate （vitamin E TPGS or TPGS） and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[methoxy（polyethylene glycol）-2000] （DSPE-PEG2000）. In this study, suberoylanilide hydroxamic acid （SAHA） and paclitaxel were used as model drugs for combination chemotherapy to enhance therapeutic efficiency in targeting mesenchyme-like triple negative breast cancer （TNBC） cells. Combination therapy of paclitaxel and SAHA in a dual drug micelle system, （P ＋ S）mic, exhibited an IC50 value of 0.52 μg/mL, which is about 5.91-fold more cytotoxic than the mere combination of free drugs （P ＋ S）. Furthermore, the （P ＋ S）mic formulation was far more effective at inhibiting cell migration by more than 3.4-fold than the control. Thus, our findings show that the co-delivery of these drugs using the micelle system greatly enhances their therapeutic effect at a lower dosage, thereby minimizing toxicity. In addition, this formulation is proved to be remarkably effective in preventing cell migration at low dosage.展开更多
文摘A polymer-based nanocarrier was developed for the co-delivery of epigenetic and chemotherapeutic drugs. The sterically stabilized hybrid micelle system uses micelles composed of D-a-tocopheryl polyethylene glycol 1000 succinate （vitamin E TPGS or TPGS） and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[methoxy（polyethylene glycol）-2000] （DSPE-PEG2000）. In this study, suberoylanilide hydroxamic acid （SAHA） and paclitaxel were used as model drugs for combination chemotherapy to enhance therapeutic efficiency in targeting mesenchyme-like triple negative breast cancer （TNBC） cells. Combination therapy of paclitaxel and SAHA in a dual drug micelle system, （P ＋ S）mic, exhibited an IC50 value of 0.52 μg/mL, which is about 5.91-fold more cytotoxic than the mere combination of free drugs （P ＋ S）. Furthermore, the （P ＋ S）mic formulation was far more effective at inhibiting cell migration by more than 3.4-fold than the control. Thus, our findings show that the co-delivery of these drugs using the micelle system greatly enhances their therapeutic effect at a lower dosage, thereby minimizing toxicity. In addition, this formulation is proved to be remarkably effective in preventing cell migration at low dosage.
