载阿霉素-全氟溴辛烷纳米级聚乳酸超声造影剂体外显像和抗肿瘤效果实验研究

Research on Doxorubicin and liquid fluorocarbon loaded nanoscale poly(lactic-co-glycolic acid) ultrasound contrast agent

目的制备以聚乳酸羟基乙酸(PLGA)为成膜材料,内载阿霉素(DOX)-全氟溴辛烷(PFOB)的纳米级超声造影剂,并评价其体外超声显像效果及体外抗肿瘤疗效。方法应用改进的单乳化水包油(O/W)溶剂挥发法制备DOXPFOB@PLGA纳米粒子,检测其一般特性及DOX体外释放行为;应用超声成像仪观察其体外超声显像效果;用细胞计数试剂盒(CCK-8)法评估其体外癌细胞杀伤效果。结果成功制备DOX-PFOB@PLGA纳米粒子,平均粒径(236. 7±45. 9)nm,分散性好; DOX的包封率为(53. 52±1. 72)%,载药量为(4. 28±0. 61)%,DOX体外释放具有PH响应性(24h累计释放量(%):PH5. 7,40%; PH7. 4,15%);体外超声显像显示纳米粒子具有造影增强效果;体外细胞实验显示其具有良好抗肿瘤效果。结论成功制备集成像与化疗功能为一体的PFOB-DOX@PLGA超声造影剂,具有良好的体外超声成像效果和体外抗肿瘤疗效。

Objective To prepare a nanoscale poly （lactic-co-glycolic acid） （PLGA） contrast agent simultaneously loaded with Doxorubicin （DOX） and Perfluorooctyl bromide （PFOB） （DOX-PFOB@ PLGA）, and to investigate the function of ultrasound imaging and anti-tumor effect in vitro. Methods PLGA nanoparticles loaded with DOX and PFOB （ DOX-PFOB@ PLGA NPs） were prepared by an adapted single emulsion oil-in-water （O/W） solvent evaporation method. The general characteristics of the nanoparticles and DOX release behavior were examined. The ultrasound diagnostic instrument was used to observe the contrast enhancement capability. Meanwhile, the cell counting kit （CCK-8） method was used to evaluate the anti-tumor effect. Results The DOX-PFOB@ PLGA nanoparticles were spherical with good dispersion, and the average diameter of （236.7 ± 45.9） nnL The encapsulation efficiency and the loading content of DOX in DOX-PFOB@ PLGA NPs was （53.52 ± 1.72）% and （4.28 ± 0. 61） %. Besides, the DOX release behavior from DOX-PFOB@ PLGA NPs was pH-dependent （24 h cumulative release （ % ） ： PH 5.7, 40% ; PH 7.4, 15% ）. In vitro experiments, the nanopartieles showed excellent ultrasound contrast enhancement effect and better anti-tumor effect. Conclusion The DOX and PFOB loaded PLGA nanoparticles have been successful fabricated, which integrated cancer imaging and chemotherapy, with good tdtrasotmd imaging capability and anti-tmuor effect in vitro.