4.7 Article

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

期刊

ACTA PHARMACEUTICA SINICA B
卷 11, 期 7, 页码 2059-2069

出版社

INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2020.11.014

关键词

Tumor targeted delivery; Truncated tissue factor (tTF); AS1411 aptamer; Thrombosis; Tumor infarction

资金

  1. National R&D Program of China [2018YFE0205300, 2018YFA0208900]
  2. National Natural Science Foundation of China [81871489, 91859118, 31730032, 31700870, 31470969, 31661130152]
  3. National Distinguished Young Scientist program (China) [31325010]
  4. K.C. Wong Education Foundation (China) [GJTD-2018-03]
  5. Beijing Municipal Natural Science Foundation (China) [7182126]

向作者/读者索取更多资源

The tumor-specific tTF delivery system developed in this study, by coupling tTF with AS1411, selectively targets tumor vascular endothelial cells, inducing tumor necrosis without significant side effects.
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 themost 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 othermoieties. We here developed a novel, tumor-specific tTFdelivery systemthrough 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. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

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