Determinants of the thrombogenic potential of multiwalled carbon nanotubes.
Determinants of the thrombogenic potential of multiwalled carbon nanotubes.
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DOI：
10.1016/j.biomaterials.2011.04.059
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发表时间：
2011-09
期刊：
影响因子：
14
通讯作者：
Torti, Suzy V.
中科院分区：
文献类型：
--
作者：
Burke, Andrew R.;Singh, Ravi N.;Carroll, David L.;Owen, John D.;Kock, Nancy D.;D'Agostino, Ralph, Jr.;Torti, Frank M.;Torti, Suzy V.
多壁碳纳米管（MWCNTs）是一种具有独特物理和电学性质的石墨碳圆柱管。多壁碳纳米管正在探索各种诊断和治疗应用。多壁碳纳米管的成功的生物医学应用将需要与正常的循环组件，包括成分的止血级联的兼容性。在本文中，我们比较了多壁碳纳米管在体外和体内的血栓形成活性。我们还评估了多壁碳纳米管的功能化对血栓形成活性的影响。在体外，MWCNT激活凝血的内在途径，如通过活化部分凝血活酶时间（aPTT）测定所测量的。通过酰胺化或羧化的官能化增强了这种促凝血活性。机制研究表明，多壁碳纳米管增强传播的内在途径通过一个非经典的机制强烈依赖于因子IX。多壁碳纳米管优先与因子IXa结合，并可为其活化提供平台。除了它们对凝血级联的影响之外，多壁碳纳米管在体外活化血小板，酰胺化的多壁碳纳米管比羧化的或原始的多壁碳纳米管表现出更大的血小板活化。然而，在体内获得相反的趋势，其中官能化倾向于减少而不是增强促凝血活性。因此，在小鼠中全身注射多壁碳纳米管后，原始多壁碳纳米管减少血小板计数，增加vWF，并增加D-二聚体。相比之下，羧化MWCNTS在体内几乎没有促凝倾向，仅引起血小板轻度和短暂的减少。酰胺化多壁碳纳米管引起血小板计数无统计学显著变化。此外，无论是羧化或酰胺化的多壁碳纳米管增加vWF或D-二聚体在小鼠血浆中。我们的结论是，在体外观察到的多壁碳纳米管的促凝血倾向不一定在体内重演。此外，功能化可以显着减弱多壁碳纳米管在体内的促凝血活性。这项工作将告知生物相容性多壁碳纳米管的系统交付的合理发展。
Multiwalled carbon nanotubes (MWCNTs) are cylindrical tubes of graphitic carbon with unique physical and electrical properties. MWCNTs are being explored for a variety of diagnostic and therapeutic applications. Successful biomedical application of MWCNTs will require compatibility with normal circulatory components, including constituents of the hemostatic cascades. In this manuscript, we compare the thrombotic activity of MWCNTs in vitro and in vivo. We also assess the influence of functionalization of MWCNTs on thrombotic activity. In vitro, MWCNT activate the intrinsic pathway of coagulation as measured by activated partial thromboplastin time (aPTT) assays. Functionalization by amidation or carboxylation enhances this procoagulant activity. Mechanistic studies demonstrate that MWCNTs enhance propagation of the intrinsic pathway via a non-classical mechanism strongly dependent on factor IX. MWCNTs preferentially associate with factor IXa and may provide a platform for its activation. In addition to their effects on the coagulation cascade, MWCNTs activate platelets in vitro, with amidated MWCNTs exhibiting greater platelet activation than carboxylated or pristine MWCNTs. However, contrasting trends are obtained in vivo, where functionalization tends to diminish rather than enhance pro-coagulant activity. Thus, following systemic injection of MWCNTs in mice, pristine MWCNTs decreased platelet counts, increased vWF, and increased D-dimers. In contrast, carboxylated MWCNTS exhibited little procoagulant tendency in vivo, eliciting only a mild and transient decrease in platelets. Amidated MWCNTs elicited no statistically significant change in platelet count. Further, neither carboxylated nor amidated MWCNTs increased vWF or D-dimers in mouse plasma. We conclude that the pro-coagulant tendencies of MWCNTs observed in vitro are not necessarily recapitulated in vivo. Further, functionalization can markedly attenuate the procoagulant activity of MWCNTs in vivo. This work will inform the rational development of biocompatible MWCNTs for systemic delivery.
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影响因子：
1.6
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