Molecularly engineered truncated tissue factor with therapeutic aptamers for tumor-targeted delivery and vascular infarction

作     者：Bozhao Li Jingyan Wei Chunzhi Di Zefang Lu Feilong Qi Yinlong Zhang Wei Sun Leong Lele Li Guangjun Nie Suping Li Bozhao Li;Jingyan Wei;Chunzhi Di;Zefang Lu;Feilong Qi;Yinlong Zhang;Wei Sun Leong;Lele Li;Guangjun Nie;Suping Li

作者机构：College of Pharmaceutical ScienceJilin UniversityChangchun 130021China CAS Key Laboratory for Biomedical Effects of Nanomaterials&NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Center of Materials Science and Optoelectronics EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China Department of Materials Science and EngineeringNational University of Singapore117575Singapore 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第7期

页      面：2059-2069页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by grants from the National R&D Program of China(2018YFE0205300,2018YFA0208900) the National Natural Science Foundation of China(81871489,91859118,31730032,31700870,31470969,31661130152) the National Distinguished Young Scientist program(31325010,China) the K.C.Wong Education Foundation(GJTD-2018-03,China) the Beijing Municipal Natural Science Foundation(7182126,China) 

主　　题：Tumor targeted delivery Truncated tissue factor(tTF) AS1411 aptamer Thrombosis Tumor infarction 

摘      要：Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer *** vascular coagulation agents,the extracellular domain of coagulation-inducing protein tissue factor,truncated tissue factor(tTF),is the most widely *** the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation,free tTF cannot be used for cancer treatment on its own but must be combined with other *** here developed a novel,tumor-specific tTF delivery system through coupling tTF with the DNA aptamer,AS1411,which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target *** administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors,thus reducing tumor blood supply and inducing tumor necrosis without apparent side *** conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.