超声介导正己酰羧甲基壳聚糖载药纳米液滴对卵巢癌细胞的抑制作用

Inhibitory effect of ultrasound-mediated drug loaded carboxymethyl hexanoyl chitosan nanodroplet on ovarian cancer cells

目的评价采用正己酰羧甲基壳聚糖制备相变型载阿霉素(DOX)纳米液滴的体外超声显像效果及抑制卵巢癌细胞生长的作用。方法将羧甲基壳聚糖与正己酸酐发生酰化反应合成正己酰羧甲基壳聚糖,采用声振乳化法制备正己酰羧甲基壳聚糖载药纳米液滴,表征其表面形态、粒径、电位;评价其体外超声显像效果,以紫外分光光度计测定药物包封率,采用CCK-8法检测卵巢癌细胞存活率,并进行统计学分析。结果成功制备正己酰羧甲基壳聚糖载药纳米液滴,镜下为大小均匀的球状物,平均粒径为(458.33±43.50)nm,包封率为(52.06±10.14)%。纳米液滴可增强超声显影效果。超声联合载药纳米液滴组的卵巢癌细胞存活率[(62.54±3.60)%]低于DOX组[(75.55±7.21)%]、载药纳米液滴组[(76.18±4.94)%]和超声组[(89.90±0.83)%],差异有统计学意义(P均<0.05)。结论超声联合正己酰羧甲基壳聚糖载药纳米液滴可有效抑制卵巢癌细胞生长,在临床诊疗中具有潜在应用价值。

Objective To evaluate the inhibitory effect of phase change doxorubicin loaded carboxymethyl hexanoyl chi- tosan nanodroplet on ovarian cancer cells, and the effect of its ultrasound image in vitro. Methods The carboxymethyl hexanoyl chitosan synthesized through the acylationreaction with carboxymethyl chitosan and hexanoic anhydride. The drug loaded carhoxymethy[ hexanoyl chitosan nanodroplets were prepared by ultrasonic emulsification. The surface morphology, particle diameter and electric potential were characterized. Ultrasound imaging of the nanodroplet was evaluated in vitro. The encapsulation efficiency was determined by ultraviolet spectrophotometry. The survival rate of ovarian cancer cell was detected using CCK-8 reagent. The statistical analysis was performed. Results The drug loaded carboxymethyl hexanoyl chitosan nanodroplet was successfully prepared which showed regular morphology in microscope, the mean diameter of （458.33 ± 43. 50） nm. The encapsulation efficiency was （ 52.06± 10.14） %. The nanodroplet could enhance ultrasonic ima- ging. The survival rate of ultrasound combined with drug loaded nanodroplet group （[62.54 ± 3.60]%） was lower than those of the free drug group （[75.55±7.21]%） and drug loaded nanodroplet group （[76.18±4. 94]%）, ultrasound group （[89.90±0.83]% ; P〈0.05）. Conclusion Ultrasound-mediated drug loaded nanodroplet can inhibit ovarian cancer cells, and has the potential for application in the clinical diagnosis and treatment.