Silver nanoparticles promote procoagulant activity of red blood cells: A potential risk of thrombosis in susceptible population

Yiying Bian, Keunyoung Kim, Thien Ngo, Inho Kim, Ok Nam Bae, Kyung Min Lim, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish
Article number9
JournalParticle and Fibre Toxicology
Volume16
Issue number1
DOIs
StatePublished - 14 Feb 2019

Bibliographical note

Funding Information:
“This research was supported by a grant (#HI16C2044) of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea.”

Publisher Copyright:
© 2019 The Author(s).

Keywords

  • Cancer
  • Red blood cells (RBCs)
  • Silver nanoparticles (AgNP)
  • Thrombosis
  • Toxicity

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