Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge.
Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge.
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DOI：
10.1289/ehp.11566
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发表时间：
2008-12
影响因子：
10.4
通讯作者：
Hoet PH
中科院分区：
文献类型：
--
作者：
Geys J;Nemmar A;Verbeken E;Smolders E;Ratoi M;Hoylaerts MF;Nemery B;Hoet PH
量子点（QD）对于体内成像具有许多可能的应用。然而，毒性数据很少。为了确定具有羧基表面涂层的量子点（羧基量子点）和具有胺表面涂层的量子点（胺量子点）的急性体内毒性，我们研究了静脉注射后的炎症特性、组织分布和促血栓形成作用。我们通过透射电子显微镜和动态光散射进行颗粒表征。将羧基-QD和胺-QD静脉内注射到小鼠中（1.44- 3，600 pmol/小鼠）。在不同的时间间隔，分析包括荧光显微镜，血细胞分析，支气管肺泡灌洗，湿和干器官重量，镉浓度在各种器官。我们通过评估抗凝肝素预处理的效果和测量血小板活化（P-选择素），以及通过暴露于QD（1.44- 1，620 pmol/mL）的鼠和人富血小板血浆中的血小板聚集，检查了体内促血栓形成作用。在3，600和720 pmol/小鼠的剂量下，QD在肺循环中引起显著的血管血栓形成，尤其是羧基QD。我们看到了表面电荷对所有测试参数的影响。QD主要存在于肺、肝和血液中。血栓并发症被废除，P-选择素不受肝素预处理动物的影响。在体外，羧基量子点和胺量子点增强腺苷二磷酸诱导的血小板聚集。在高剂量下，QD引起肺血管血栓形成，最有可能是通过接触激活激活凝血级联反应。我们的研究强调了在将QD用于人类应用之前，需要对其进行仔细的安全性评估。此外，很明显，表面电荷是纳米毒性的一个重要参数。
Quantum dots (QDs) have numerous possible applications for in vivo imaging. However, toxicity data are scarce. To determine the acute in vivo toxicity of QDs with carboxyl surface coating (carboxyl-QDs) and QDs with amine surface coating (amine-QDs), we investigated the inflammatory properties, tissue distribution, and prothrombotic effects after intravenous injection. We performed particle characterization by transmission electron microscopy and dynamic light scattering. Carboxyl-QDs and amine-QDs were intravenously injected in mice (1.44–3,600 pmol/mouse). At different time intervals, analyses included fluorescence microscopy, blood cell analysis, bronchoalveolar lavage, wet and dry organ weights, and cadmium concentration in various organs. We examined the prothrombotic effects in vivo by assessing the effect of pretreatment with the anticoagulant heparin and by measuring platelet activation (P-selectin), and in vitro by platelet aggregation in murine and human platelet-rich plasma exposed to QDs (1.44–1,620 pmol/mL). At doses of 3,600 and 720 pmol/mouse, QDs caused marked vascular thrombosis in the pulmonary circulation, especially with carboxyl-QDs. We saw an effect of surface charge for all the parameters tested. QDs were mainly found in lung, liver, and blood. Thrombotic complications were abolished, and P-selectin was not affected by pretreatment of the animals with heparin. In vitro, carboxyl-QDs and amine-QDs enhanced adenosine-5′-diphosphate–induced platelet aggregation. At high doses, QDs caused pulmonary vascular thrombosis, most likely by activating the coagulation cascade via contact activation. Our study highlights the need for careful safety evaluation of QDs before their use in human applications. Furthermore, it is clear that surface charge is an important parameter in nanotoxicity.
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影响因子：
10.4
作者：
Hardman R
通讯作者：
Hardman R
DOI：
10.1073/pnas.152463399
发表时间：
2002-10-01
影响因子：
11.1
作者：
Åkerman, ME;Chan, WCW;Ruoslahti, E
通讯作者：
Ruoslahti, E
DOI：
10.1164/rccm.200110-026oc
发表时间：
2002-10-01
影响因子：
24.7
作者：
Nemmar, A;Hoylaerts, MF;Nemery, B
通讯作者：
Nemery, B
影响因子：
56.9
作者：
Larson, DR;Zipfel, WR;Webb, WW
通讯作者：
Webb, WW
影响因子：
46.9
作者：
Jaiswal, JK;Mattoussi, H;Simon, SM
通讯作者：
Simon, SM