Dendrimer-induced leukocyte procoagulant activity depends on particle size and surface charge
Dendrimer-induced leukocyte procoagulant activity depends on particle size and surface charge
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DOI：
10.2217/nnm.11.105
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发表时间：
2012-02-01
期刊：
影响因子：
5.5
通讯作者：
McNeil, Scott E.
中科院分区：
文献类型：
--
作者：
Dobrovolskaia, Marina A.;Patri, Anil K.;McNeil, Scott E.
目的：与诱导白细胞促凝活性（PCA）相关的致血栓性是脓毒症和癌症的常见并发症。由于纳米颗粒越来越多地用于药物递送，它们与凝血系统的相互作用是安全性评估的重要组成部分。本研究的目的是研究纳米颗粒的理化性质对白细胞PCA的影响，并深入了解PCA的诱导机制。材料和方法：共12个配方的聚酰胺-胺（PAMAM）树枝状聚合物，不同的大小和表面电荷，在体外进行了研究，使用结晶时间测定。结果：无论其大小，阴离子和中性树枝状大分子在体外不诱导白细胞PCA。阳离子颗粒诱导PCA的大小和电荷依赖的方式。PCA的诱导机制与阿霉素相似。还发现阳离子树枝状聚合物加剧内毒素诱导的PCA。结论：PAMAM树枝状大分子诱导白细胞PCA依赖于粒子的大小、电荷和表面基团的密度。
Aims: Thrombogenicity associated with the induction of leukocyte procoagulant activity (PCA) is a common complication in sepsis and cancer. Since nanoparticles are increasingly used for drug delivery, their interaction with coagulation systems is an important part of the safety assessment. The purpose of this study was to investigate the effects of nanoparticle physicochemical properties on leukocyte PCA, and to get insight into the mechanism of PCA induction. Materials & Methods: A total of 12 formulations of polyamidoamine (PAMAM) dendrimers, varying in size and surface charge, were studied in vitro using recalcification time assay. Results: Irrespective of their size, anionic and neutral dendrimers did not induce leukocyte PCA in vitro. Cationic particles induced PCA in a size- and charge-dependent manner. The mechanism of PCA induction was similar to that of doxorubicin. Cationic dendrimers were also found to exacerbate endotoxin-induced PCA. Conclusion: PAMAM dendrimer-induced leukocyte PCA depends on particle size, charge and density of surface groups.