Self-Titrating Anticoagulant Nanocomplexes That Restore Homeostatic Regulation of the Coagulation Cascade
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- 作者：Kevin Y. Lin ; Justin H. Lo ; Nikita Consul ; Gabriel A. Kwong ; Sangeeta N. Bhatia
- 刊名：ACS Nano
- 出版年：2014
- 出版时间：September 23, 2014
- 年：2014
- 卷：8
- 期：9
- 页码：8776-8785
- 全文大小：660K
- ISSN：1936-086X
文摘
Antithrombotic therapy is a critical portion of the treatment regime for a number of life-threatening conditions, including cardiovascular disease, stroke, and cancer; yet, proper clinical management of anticoagulation remains a challenge because existing agents increase the propensity for bleeding in patients. Here, we describe the development of a bioresponsive peptide鈥損olysaccharide nanocomplex that utilizes a negative feedback mechanism to self-titrate the release of anticoagulant in response to varying levels of coagulation activity. This nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs circulate inactively, neither releasing anticoagulant nor significantly prolonging bleeding time. However, in response to life-threatening pulmonary embolism, nanoSTATs locally release their drug payload and prevent thrombosis. This autonomous negative feedback regulator may improve antithrombotic therapy by increasing the therapeutic window and decreasing the bleeding risk of anticoagulants.