Nanodiamonds activate blood platelets and induce thromboembolism

Nanomedicine (Lond). 2014 Mar;9(3):427-40. doi: 10.2217/nnm.13.23. Epub 2013 Apr 30.

Abstract

Aim: Nanodiamonds (NDs) have been evaluated for a wide range of biomedical applications. Thus, thorough investigation of the biocompatibility of NDs has become a research priority. Platelets are highly sensitive and are one of the most abundant cell types found in blood. They have a central role in hemostasis and arterial thrombosis. In this study, we aim to investigate the direct and acute effects of carboxylated NDs on platelet function.

Methods: In this study, pro-coagulant parameters such as platelet aggregability, intracellular Ca(2+) flux, mitochondrial transmembrane potential (ΔΨm), generation of reactive oxygen species, surface exposure of phosphatidylserine, electron microscopy, cell viability assay and in vivo thromboembolism were analyzed in great detail.

Results: Carboxylated NDs evoked significant activation of human platelets. When administered intravenously in mice, NDs were found to induce widespread pulmonary thromboembolism, indicating the remarkable thrombogenic potential of this nanomaterial.

Conclusion: Our findings raise concerns regarding the putative biomedical applications of NDs pertaining to diagnostics and therapeutics, and their toxicity and prothrombotic properties should be critically evaluated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Calcium / metabolism
  • Carboxylic Acids / administration & dosage
  • Carboxylic Acids / adverse effects
  • Carboxylic Acids / chemistry
  • Cell Survival / drug effects
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Nanodiamonds / administration & dosage
  • Nanodiamonds / adverse effects*
  • Nanodiamonds / chemistry*
  • Nanodiamonds / ultrastructure
  • P-Selectin / analysis
  • P-Selectin / metabolism
  • Platelet Aggregation / drug effects*
  • Reactive Oxygen Species / metabolism
  • Thromboembolism / blood
  • Thromboembolism / chemically induced*
  • Thromboembolism / metabolism

Substances

  • Carboxylic Acids
  • Nanodiamonds
  • P-Selectin
  • Reactive Oxygen Species
  • Calcium