凝血酶响应性纤溶纳米胶囊的制备及性能研究
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- 英文论文题名：Preparation and performance studies on thrombin-responsive fibrinolytic nanocapsules
- 论文作者：李聪 ; 杜慧 ; 李丹 ; 陈红
- 英文论文作者：Cong Li ; Hui Du ; Dan Li ; Hong Chen ; College of Chemistry ; Chemical Engineering and Materials Science ; Soochow University
- 年：2016
- 作者机构：苏州大学材料与化学化工学部;
- 论文关键词：组织型纤溶酶原激活剂 ; 凝血酶响应性 ; 纳米胶囊 ; 纤溶
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第三十八分会：纳米生物效应与纳米药物化学
- 语种：中文
- 分类号：TQ460.6
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第三十八分会 ; 纳米生物效应与纳米药物化学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：194k
- 原文格式：D
- 会议级别：全国
摘要
组织型纤溶酶原激活剂(t-PA)是血纤维蛋白溶酶原(Plg)的主要生理激活剂,通过将Plg激活为纤溶酶而实现对纤维蛋白(初级血栓)的溶解[1]。因此,t-PA常用于临床治疗急性心肌梗塞等血栓症。然而,t-PA在血液中半衰期极短,需大剂量给药才能够有效溶栓,但这同时也伴随着出血等严重的并发症。以载体封装t-PA并使其在血栓部位响应性释放则可以有效解决以上问题[2]。为此,本研究构建了一种具有血栓响应性纤溶活性的纳米胶囊。通过在t-PA表面静电吸附单体丙烯酰胺与N-(3-氨基丙基)甲基丙烯酰胺,原位自由基聚合并交联,形成包裹t-PA的水凝胶纳米胶囊。针对血栓生成时伴随着凝血酶产生这一特征性血液微环境的变化,选用可被凝血酶酶切的多肽作为交联剂,从而赋予纳米胶囊血栓响应性降解并释放t-PA的性能。利用透射电子显微镜观察到该纳米胶囊具有15-20nm的球状结构;t-PA显色底物活性测试和血浆复钙化实验结果表明该纳米胶囊成功掩蔽了t-PA活性;而当凝血酶存在时,纳米胶囊瓦解并释放t-PA,从而表现出显著的溶栓活性。
Tissue plasminogen activator(t-PA) is the primary physiological activator of plasminogen. It participates in the fibrinolytic process by converting plasminogen to plasmin. Thus, t-PA is widely used as a thrombolytic drug in the treatment of thrombotic diseases. However, t-PA has extremely short half-life, which require administration in large doses to obtain therapeutic effects, and as a consequence, inevitably leads to significant incidence of hemorrhagic complications. To solve this problem, a thrombosis-responsive fibrinolytic nanocapsule(NC) is developed in the present study. The fibrinolytic NCs were prepared by adsorbing monomers on the surface of t-PA followed by in situ polymerization and crosslinking to form a hydrogel shell. A thrombin-cleavable peptide was used as cross-linker to endow NCs with thrombosis-responsive degradation properties. TEM images showed spherical NCs with diameter of ~18 nm. Enzymatic activity and plasma recalcification assay indicated that the activity of t-PA was shielded by the hydrogel shell, while in the presence of thrombin, the shell was disrupted and fibrinolytic activity was recovered.
Tissue plasminogen activator(t-PA) is the primary physiological activator of plasminogen. It participates in the fibrinolytic process by converting plasminogen to plasmin. Thus, t-PA is widely used as a thrombolytic drug in the treatment of thrombotic diseases. However, t-PA has extremely short half-life, which require administration in large doses to obtain therapeutic effects, and as a consequence, inevitably leads to significant incidence of hemorrhagic complications. To solve this problem, a thrombosis-responsive fibrinolytic nanocapsule(NC) is developed in the present study. The fibrinolytic NCs were prepared by adsorbing monomers on the surface of t-PA followed by in situ polymerization and crosslinking to form a hydrogel shell. A thrombin-cleavable peptide was used as cross-linker to endow NCs with thrombosis-responsive degradation properties. TEM images showed spherical NCs with diameter of ~18 nm. Enzymatic activity and plasma recalcification assay indicated that the activity of t-PA was shielded by the hydrogel shell, while in the presence of thrombin, the shell was disrupted and fibrinolytic activity was recovered.
引文
[1]Dan Li a,b;Hong Chen b;John L.Brash b,c.Colloids and Surfaces B:Biointerfaces.2011,86(1):1.
[2]Shahriar Absar a;Suna Choi a;Victor C.Yang b;Young M.Kwon a.Journal of Controlled Release.2014,177:42.
[2]Shahriar Absar a;Suna Choi a;Victor C.Yang b;Young M.Kwon a.Journal of Controlled Release.2014,177:42.