中文摘要：

目的以高分子聚合物聚乳酸-羟基乙酸（PLGA）为成膜材料制备携抗HER-2抗体空心纳米靶向超声造影剂,并考察其体外寻靶及显像效果。方法以樟脑为致孔剂,通过改进的双乳化溶剂挥发法制备PLGA纳米超声造影剂,利用扫描电子显微镜、透射电子显微镜及激光粒度仪对其一般特性进行表征;并用碳二亚胺法将造影剂与抗HER-2抗体耦联制备携抗HER-2抗体的PLGA靶向纳米超声造影剂,用激光共聚焦扫描显微镜对其体外寻靶能力进行初步评估,考察其体外成像效果。结果 PLGA纳米超声造影剂的平均粒径为（152.00±58.08）nm,粒子呈规则球形,大小均一,分散性好。体外寻靶实验显示,携抗HER-2抗体的PLGA靶向造影剂较多牢固地聚集到乳腺癌细胞表面。体外成像实验显示,PLGA靶向纳米超声造影剂显像呈细腻均匀的点状高回声,后方回声未见明显衰减。结论本研究成功制备了携抗HER-2抗体的PLGA靶向纳米超声造影剂,其能与HER-2受体高表达的乳腺癌细胞体外特异性靶向结合,且体外显像效果较好。

英文摘要：

Objective To develop the targeted ultrasound contrast agent with poly（lactic-co-glycolic acid）（PLGA） nanoparticles which attach to HER-2 receptor, and to investigate its affinity for breast cancer cells in vitro. Methods The PLGA nanoscale ultrasound contrast agent was prepared by modified double-emulsion solvent evaporation method. Camphor as sublimable porogen was added to render the nanoparticles hollow and enable efficient perfluoropropane（C3F8） gas introduction. The physicochemical properties of PLGA nanoparticles were characterized by electronic microscopies and dynamic laser scattering. The nanoparticles were surface-conjugated to an anti-HER-2 antibody（Herceptin） for specific binding to breast cancer SKBr3 cells overexpressing HER-2 receptors. Laser confocal microscope was used to assess the nanoparticle-cell targeting binding. In vitro ultrasound imaging of HER-2-targeted PLGA nanoparticles were investigated under high frequency imaging condition. Results The PLGA nanoparticles were observed with regular morphology, good dispersion, and uniform size with average size of（152.00±58.08） nm. HER-2-positive breast cancer SKBr3 cells demonstrated substantial staining after incubation with HER-2-targeted PLGA nanoparticles, while minimal staining was found in HER-2-negative MDA-MB-231 cells, indicating receptor-specific binding of the antibody-conjugated PLGA nanoparticles. Moreover, in vitro ultrasound imaging of targeted PLGA nanoparticles showed obvious signal enhancement. Conclusion The PLGA nanoparticles targeted to HER-2 receptors of breast cancer cells have been prepared successfully, which can bind to breast cancer cells effectively. The preliminary in vitro study demonstrates that HER-2-targeted PLGA nanoparticles have excellent ultrasound imaging capability.