制备叶酸受体靶向载阿霉素/黑色素多功能造影剂及体外超声/光声显像

Preparation and in vitro ultrasound/photoacoustic imaging of folate receptor-targeted,doxorubicin and melanin-loaded

目的制备叶酸受体靶向载阿霉素/黑色素的多功能造影剂,评估其基本特性、体外细胞靶向能力、超声和光声显像效果以及对人乳腺癌MDA-MB-231细胞增殖活力的影响。方法采用单乳化法和冷冻干燥减压充入C3F8气体的方法制备叶酸受体靶向载阿霉素/黑色素多功能造影剂,以马尔文激光仪检测其平均粒径及表面电位,应用紫外-可见光分光光度法测量阿霉素载药量,于凝胶模型中观察其体外超声、光声增强显影能力,以人乳腺癌MDA-MB-231细胞验证其体外细胞靶向能力和细胞增殖活力的影响。结果叶酸受体靶向载阿霉素/黑色素脂质多功能造影剂平均粒径为(659.60±27.56)nm,Zeta电位为(-38.90±4.00)mV,阿霉素载药率为85.72μg/mg。叶酸受体靶向造影剂大量聚集在MDA-MB-231细胞表面,具有较好的体外超声、光声显像能力,对MDA-MB-231细胞增殖有显著抑制作用。结论叶酸受体靶向载阿霉素/黑色素多功能造影剂是集靶向治疗、超声和光声多模态显像于一体的多功能造影剂,有望成为乳腺癌精准显像和治疗的理想分子探针。

Objective To prepare the folate receptor-targeted,doxorubicin and melanin-loaded multifunctional contrast media,and to observe its characteristics,targeting,imaging performance and cell toxicity on human MDA-MB-231 cell lines in vitro.Methods The folate receptor-targeted,doxorubicin and melanin-loaded multifunctional contrast media was prepared using single emulsion method and freeze-drying and C3 F8-inflation.Its size and drug loading efficiency were measured with Malvern instrument and UV-visible spectrophotometry.Its enhanced respectively ultrasound and photoacoustic imaging were observed in vitro model.The targeting performance of contrast media and its cell toxicity were checked after co-incubated with human MDA-MB-231 cell lines.Results The average diameter of contrast media was（659.60±27.56）nm,Zeta potential was（-38.90±4.00）mV,and the drug loading capacity was 85.72μg/mg.In vitro,the targeting experiment showed that a large number of folate receptor-targeted contrast media were aggregated and adhered firmly to the MDA-MB-231 cells.The folate receptor-targeted contrast media significantly inhibited the proliferation of human MDA-MB-231 cells.The ultrasound and photoacoustic imaging of folate receptor-targeted contrast media were significantly enhanced.Conclusion The folate receptor-targeted,doxorubicin and melanin-loaded multifunctional contrast media is a set of targeting treatment,enhancing ultrasound and photoacoustic imaging,having potential of perfect molecular probe for targeting imaging and treatment of human breast cancer.