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

摘要

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-FRT-Dox 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-FRT-Dox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.