RGD4C修饰的铁蛋白纳米笼用于大鼠肝星状细胞的靶向药物输送

RGD4C modified ferritin nanocages for rat hepatic stellate cells-targeted drug delivery

目的:制备RGD4C修饰的铁蛋白纳米笼(RGD4C-FRT),并用于大鼠肝星状细胞(HSC-T6)的靶向药物输送。方法:对RGD4C修饰的人铁蛋白H亚基进行表达和纯化;采用离子通道的方法,将阿霉素(Dox)包裹到RGD4C-FRT空腔,即为RGD4C-FRT-Dox;荧光显微镜检测RGD4C-FRT-Dox对HSC-T6的靶向性。结果:透射电镜检测显示,RGD4C-FRT为中空球形、粒径均一、分散性好;RGD4C-FRT和RGD4C-FRTDox的平均粒径分别为12.57 nm和20.13 nm;RGD4C-FRT-Dox的包封率和载药量分别为77.32%和15.88%;HSC-T6对RGD4C-FRT-Dox有明显摄取,并且能够被RGD4C-FRT空载体阻断。结论:RGD4C-FRTDox对HSC-T6有特异靶向性,可进一步在动物水平验证其治疗肝纤维化的有效性。

Objective The purpose of this study was to prepare RGD4C modified ferritin nanocages （RGD4C-FRT） for targeted drug delivery to rat hepatic stellate cells （HSC-T6）. Methods RGD4C modified human H-chain ferritin was expressed and purified. Doxorubicin （Dox） was encapsulated into the cavity of RGD4C- FRT through ion channels, which resulted in RGD4C-FRT-Dox. The target of RGD4C-FRT-Dox to HSC-T6 was detected using fluorescence microscopy. Results Transmission electron microscopy showed that RGD4C-FRT was hollow spherical-structured with uniform size and good dispersion. The average particle diameters of RGD4C-FRT and RGD4C-FRT-Dox were 12.57 nm and 20.13 nm, respectively. The drug encapsulation efficiency and loading percentage of RGD4C-FRT-Dox were 77.32% and 15.88% respectively. RGD4C-FRT-Dox was significantly uptaken by HSC-T6, and the uptake could be blocked by the empty carrier RGD4C-FRT. Conclusion RGD4C- FRT-Dox can specifically target HSC-T6. Further animal experiments are needed to inspect its therapeutic effect on liver fibrosis.