| 张海涛 范晓东 索荣田 杨臻 张万斌 李辉 李飞.超声和pH 响应的药物共转运纳米胶束的制备及其生物学性能初探[J].现代生物医学进展英文版,2015,15(33):6559-6563. |
| 超声和pH 响应的药物共转运纳米胶束的制备及其生物学性能初探 |
| Ultrasound and pH Dual Responsive Drug co-delivery Nanoparticles:Preparation and Biological Evaluation |
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| DOI： |
| 中文关键词: 阿霉素 石胆酸 共转运纳米粒 超声 |
| 英文关键词: Doxorubicin Lithocholic acid Co-delivery nanoparticle Ultrasound |
| 基金项目:国家自然科学基金项目（21274116，21374088） |
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| 中文摘要: |
| 目的：制备一种超声和pH双重响应的同时载有阿霉素(DOX)与石胆酸(LA)的纳米胶束，实现两种药物的共转运。方法：将叠
氮化的石胆酸(LA-(N3)2)与两个丙炔胺化茁-环糊精(茁-CD-C≡ CH)通过点击反应结合，得到一种两亲性beta- 环糊精二聚体(LA-(CD)
2)。该环糊精二聚体在水溶液中发生自组装，同时包裹疏水性药物阿霉素，最终得到阿霉素与石胆酸共转运的纳米胶束
(LA-CD2/DOX)。通过核磁共振光谱和飞行时间质谱表征LA-(CD)2的结构，透射电镜(TEM)和动态光散射(DLS)表征共转运纳米
粒的形貌和大小，动态透析法模拟体外释药，监测在不同pH 值和超声作用下纳米胶束的释药特性，同时采用人口腔表皮样癌细
胞(KB 细胞)测定LA-(CD)2/DOX的细胞毒性。结果：①经核磁共振和飞行时间质谱表征LA-(CD)2成功合成。②透射电镜和动态
光散射证实LA-(CD)2自组装成形态规整的纳米胶束，Dz=128 nm，PDI=0.21。③体外释药实验结果表明DOX的释药具有pH和超
声双重响应性，而LA 的释药只具有pH响应性。④细胞实验证实LA-CD2/DOX的细胞毒性高于DOX 和LA。结论：LA-(CD)
2/DOX 可有望成为一种pH和超声双重响应的抗肿瘤药物共转运纳米载体。 |
| 英文摘要: |
| Objective:To Prepare an ultrasound and pH dual-responsive nanoparticles for co-delivery of doxorubicin (DOX) and
lithocholic acid (LA).Methods:An amphiphilic 茁-cyclodextrin (茁-CD) dimer, namely LA- (CD)2, was synthesized through the click
reaction between LA- (N3)2 and mono-6-deoxy-6-alkyne 茁-CD (茁-CD-C≡ CH) monomers. In an aqueous solution at roomtemperature,
LA- (CD)2 self-assembles into nanoparticles and the hydrophobic doxorubicin was simultaneously encapsulated into the nanoparticles，
leading the formation of LA and DOX co-delivery nanoparticles. The structure of LA- (CD)2 was confirmed by 1H NMR spectroscopy
and MALDI-TOF-MS, and the transmission electron microscopy (TEM), dynamic light scattering (DLS) and 1H NMR spectroscopic
measurements were conducted to obtain a deeper insight into the morphology and the size of the co-delivery. Furthermore the drug
release properties were determined by dynamic dialysis method. The cellular uptake and cytotoxicity were assessed by using human oral
epidermoid carcinoma KB cells as in vitro cell model.Results:① LA- (CD)2 was prepared successfully. ② The TEM and DLS results
indicated that LA- (CD)2 could self-assemble into special nanoparticles with Dz=128 nm and PDI=0.21. ③ In vitro DOX release from
LA-CD2/DOX nanoparticles occurred at a faster rate at acidic pH compared with neutral pH (7.4) and the released could be enhanced by
ultrasound. However, the LA release rated was only controlled by pH values. ④ The LA-CD2/DOX co-delivery nanoparticle were much
more toxic against KB cells, compared with either free DOX or LA (P<0.05).Conclusion:The pH and ultrasound dual sensitive LA-(CD)
2/DOX nanoparticles are promising co-delivery carriers for anti-tumor drug delivery. |
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