Two-step Tumor Targeting Of RBC Delivery System Based On Click Chemistry

Targeted tumor detection and drug delivery have always been the focus of oncology study.However,traditional targeted therapy has been facing with the problems of limited targeting sites and weak interaction.To solve these limitations,we constructed a two-step tumor targeting system with RBC-membrane-derived vesicles based on Click chemistry,which was proved to be highly specific and efficient,with less toxic and side effects compared to the traditional therapies.Three issues were primarily investigated in this study:1.Construction of RBC-membrane based drug delivery system. RBC-membrane-derived vesicles were obtained with hyposmosis using red blood cells.The vesicles were then extruded through polycarbonate porous membranes for vesicles with particle size of 100 nm and the acquired vesicles were encapsulated with azidoethyl-choline and indocyanine Green respectively.The construction and characteristics of RBC-membrane-derived vesicles were evaluated with TEM,Zetasizer Nano ZS,and CLSM.2.Evaluation of cell azidation and two-step tumor targeting in vitro.The phospholipid of MCF-7 cells was azidated by fusing with AECho modifie d RBC-membrane-derived vesicles.In turn,the azidated tumor cells could be specifically targeted by the RBC-membrane-derived vesicles at 37°C,within just one hour.3.Evaluation of drug distribution in vivo.The azidation of in vivo tumor cells by AECho were demonstrated by microt omy.To evaluate the efficiency of the new system,in vivo imaging was used.The result demonstrated that the drug gathered around the tumor cells within one hour after drug delivery in the two-step tumor targeting system,which exhibited ideal therapeutic effect after irradiated by near infrared laser.