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
A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly（ethylene glycol）-blo...A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly（ethylene glycol）-block- poly（4-vinylpyridine-co-N-heptyl-4-vinylpyridine） （PEG-b-P（4VP-co-4VPHep））, tetrakis（4-sulfonatophenyl）porphinato iron（II） （Fe（II）TPPS） and β-cyclodextrin （β-CD）. The μ-oxo dimer of Fe（II）TPPS was successfully inhibited because the Fe（II）TPPS was included into the cavities of β-CDs through host-guest interaction. Fe（II）TPPS coordinated with pyridine groups functions as the active site to reversibly bind dioxygen. In adition, the host-guest inclusion （β-CD/Fe（II）TPPS） was encapsulated in the hydrophobic core of the complex micelle and tightly fixed by P4VP chains. The hydrophilic PEG blocks stretched in aqueous solution to constitute the shells which stabilize the structure of the complex micelle as well as endow the complex micelle with sufficient blood circulation time. Dioxygen can be bound to the Fe（II）TPPS located in the confined space and excellent reversibility of the binding-release process of dioxygen can be achieved. The quaternary amine N-heptyl-4-vinylpyridine can coerce abundant S2O4^2- ions into the core of the complex micelle to facilitate the self-reduction process. Dioxygen adducts （Fe（II）TPPS（O2）） were effectively protected by the double hydrophobic barriers constructed by the cavity of the cyclodextrin and the core of the complex micelle which enhances the ability to resist nucleophilic molecules. Therefore, the rationally designed amphiphilic structure can work as a promising artificial O2 carrier. Potentially, the complex micelle can be expected to improve the treatment of diseases linked with hypoxia.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.
文摘A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly（ethylene glycol）-block- poly（4-vinylpyridine-co-N-heptyl-4-vinylpyridine） （PEG-b-P（4VP-co-4VPHep））, tetrakis（4-sulfonatophenyl）porphinato iron（II） （Fe（II）TPPS） and β-cyclodextrin （β-CD）. The μ-oxo dimer of Fe（II）TPPS was successfully inhibited because the Fe（II）TPPS was included into the cavities of β-CDs through host-guest interaction. Fe（II）TPPS coordinated with pyridine groups functions as the active site to reversibly bind dioxygen. In adition, the host-guest inclusion （β-CD/Fe（II）TPPS） was encapsulated in the hydrophobic core of the complex micelle and tightly fixed by P4VP chains. The hydrophilic PEG blocks stretched in aqueous solution to constitute the shells which stabilize the structure of the complex micelle as well as endow the complex micelle with sufficient blood circulation time. Dioxygen can be bound to the Fe（II）TPPS located in the confined space and excellent reversibility of the binding-release process of dioxygen can be achieved. The quaternary amine N-heptyl-4-vinylpyridine can coerce abundant S2O4^2- ions into the core of the complex micelle to facilitate the self-reduction process. Dioxygen adducts （Fe（II）TPPS（O2）） were effectively protected by the double hydrophobic barriers constructed by the cavity of the cyclodextrin and the core of the complex micelle which enhances the ability to resist nucleophilic molecules. Therefore, the rationally designed amphiphilic structure can work as a promising artificial O2 carrier. Potentially, the complex micelle can be expected to improve the treatment of diseases linked with hypoxia.
