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β-环糊精（B—CD—C-=CH）通过点击反应结合，得到一种两亲性p一环糊精二聚体（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柬（LA—CWDOX）。通过核磁共振光谱和飞行时间质谱表征LA-（cD）z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（KS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柬，Dz=128nm，PDI=0．21。⑧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-CDE／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 β-cyelodextrin （β-CD） dimer, namely LA- （CD）2, was synthesized through the click reaction between LA- （N3）2 and mono-6-deoxy-6-alkyne β-CD （β-CD-C- CH） monomers. In an aqueous solution at room temperature, 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. ②The 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. ④The 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.