Molecularly engineered truncated tissue factor with therapeutic aptamers for tumor-targeted delivery and vascular infarction.
10.1016/j.apsb.2020.11.014
- Author:
Bozhao LI
1
;
Jingyan WEI
1
;
Chunzhi DI
2
;
Zefang LU
2
;
Feilong QI
2
;
Yinlong ZHANG
2
;
Wei Sun LEONG
3
;
Lele LI
2
;
Guangjun NIE
2
;
Suping LI
2
Author Information
1. College of Pharmaceutical Science, Jilin University, Changchun 130021, China.
2. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
3. Department of Materials Science and Engineering, National University of Singapore, 117575, Singapore.
- Publication Type:Journal Article
- Keywords:
AS1411 aptamer;
Thrombosis;
Truncated tissue factor (tTF);
Tumor infarction;
Tumor targeted delivery
- From:
Acta Pharmaceutica Sinica B
2021;11(7):2059-2069
- CountryChina
- Language:English
-
Abstract:
Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy. Among vascular coagulation agents, the extracellular domain of coagulation-inducing protein tissue factor, truncated tissue factor (tTF), is the most widely used. Since 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 moieties. We 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 cells. Systemic 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 effects. This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.
