Silver nanoparticles promote procoagulant activity of red blood cells: a potential risk of thrombosis in susceptible pop
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RESEARCH
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Silver nanoparticles promote procoagulant activity of red blood cells: a potential risk of thrombosis in susceptible population Yiying Bian1, Keunyoung Kim1, Thien Ngo1, Inho Kim2, Ok-Nam Bae3, Kyung-Min Lim4 and Jin-Ho Chung1*
Abstract Background: Silver nanoparticles (AgNP) are widely used in medical practices owing to their distinct antibacterial, antiviral and anticancer activities. However, with increasing use of AgNP, concerns over its potential toxicity are also escalating. Here, we demonstrated the potential thrombotic effect of AgNP which was mediated by the procoagulant activity of red blood cells (RBCs). Results: In freshly isolated human RBCs, AgNP, but not silver microparticles (AgMP), elicited morphological changes, phosphatidylserine (PS) exposure and microvesicles (MV) generation, the key indicators of procoagulant activity in RBCs at concentration ranges (≤ 100 μg/mL) that were free of significant hemolysis. In line with this, AgNP potentiated thrombin generation and adherence of RBCs to endothelial cells, while AgMP did not. Oxidative stress, intracellular calcium increase and ATP depletion were found to underlie the procoagulant effects of AgNP, which led to altered activity of membrane aminophospholipid translocases. These in vitro findings were well reproduced in rat in vivo, where intravenously exposure to AgNP promoted venous thrombosis significantly. Of note, RBCs isolated from cancer patients, who inherently convey the risk of thrombogenesis, were more sensitive to the procoagulant effects of AgNP. In addition, AgNP significantly potentiated the procoagulant effects of a chemotherapeutic drug, paclitaxel. Conclusion: Collectively, these results suggest that AgNP may have prothrombotic risks by promoting procoagulant activity of RBCs and caution shall be taken for its use in the population sensitive to thrombosis like cancer patients. Keywords: Silver nanoparticles (AgNP), Toxicity , Thrombosis , Red blood cells (RBCs) , Cancer
Background Silver nanoparticles (AgNP) are widely used for therapeutic interventions and diagnosis in medical practices and have gained increasing popularity as drug carriers, nanoprobes, bio-imaging and labeling agents [1, 2]. Along with increasing application of AgNP in nanomedicine, however, concerns are also escalating over its potential toxicity against human health [3–5]. Potential adverse effects of AgNP against human health have been first illuminated at a concentration range of 25 ~ 500 μg/mL for 10 ~ 72 h duration in vitro, with respect to its cytotoxicity on human cell lines, reactive oxygen species (ROS) generation, oxidative stress, cell-cycle arrest, pro-apoptotic effects and genotoxicity [5–7]. * Correspondence: [email protected] 1 College of Pharmacy, Seoul National University, Seoul 151-742, South Korea Full list of author information is available at the end of the article
AgNP readily enters the systemic circulation [8–10]. Accordingly, much attention has been paid to the potential cardiovascular toxicity of AgNP due to an ea
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