载多烯紫杉醇及酞菁锌并靶向乳腺癌多功能分子探针体外光声显像特性及寻靶能力

摘要

目的 观察载多烯紫杉醇及酞菁锌并靶向乳腺癌多功能分子探针的体外光声显像特性及寻靶能力.方法 采用双乳化法及碳二亚胺法制备载多烯紫杉醇及酞菁锌并连接RDG靶向肽的多功能分子探针.检测探针的一般物理特性、多烯紫杉醇及酞菁锌包封率及载药量、与RGD连接情况及体外寻靶能力,观察其体外光声显像情况、体外释放特性及体外抑制乳腺癌细胞的能力.结果 成功制备靶向载多烯紫杉醇及酞菁锌的多功能分子探针,平均粒径(266.00±65.85)nm,表面电位(-29.20±6.27)mV;多烯紫杉醇包封率及载药量分别为(88.00±0.32)％、(34.92±0.02) μg/mg,酞菁锌包封率及载药量分别为(97.25±0.22)％、(30.87±0.11)μg/mg;靶向载多烯紫杉醇及酞菁锌纳米粒具有一定缓释效应,且呈明显光声信号,并随酞菁锌含量增加而增强.流式细胞仪检测RGD肽与靶向载多烯紫杉醇及酞菁锌纳米粒连接率为89.19％.激光辐照靶向载多烯紫杉醇及酞菁锌纳米粒后,乳腺癌细胞凋亡率明显增高.结论 载多烯紫杉醇及酞菁锌并靶向乳腺癌多功能分子探针呈明显光声信号,并具备乳腺癌细胞靶向能力,可通过光声介导抑制乳腺癌细胞增殖.%Objective To investigate the targeting ability and photoacoustic imaging of novel nanoparticle probe loaded with ZnPc and docetaxel.Methods The polymeric nanoparticles probe loaded with ZnPc and docetaxel were fabricated using double emulsion method.RGDfK was modified on the surface for breast carcinoma targeting by carbodiimide method.The encapsulating ratio (ER) and drug loading (DL) of ZnPc and docetaxel were assessed.The modification rate and targeting ability of molecular probe were tested in vitro,and the photoacoustic imaging and drug release profiles were observed.Results The probes were loaded with ZnPc and docetaxel efficiently and successfully.The size of novel nanoparticle loaded with ZnPc and docetaxel was (266.00 ± 65.85)nm,and the surface potential was (-29.20± 6.27)mV.ER and DL of docetaxel was (88.00±0.32)％ and (34.92±0.02)μg/mg,of ZnPc was (97.25±0.22)％ and (30.87±0.11)μg/mg,respectively.The probes had certain sustained slow release effect and showed obvious photoacoustic signals,which enhanced with the increase of the content of ZnPc.Flow cytometry detection results showed that the RGDfk modification rate was 89.19％.The apoptotic rate of novel nanoparticle loaded with ZnPc and docetaxel targeting breast carcinoma increased after the laser irradiation in vitro.Conclusion The new polymeric multifunctional nanoparticles probe has an ideal size and good photoacoustic signals,also the ability to target breast carcinoma cells and inhibit the proliferation of breast carcinoma cells efficiently.