Inhibition of phosphoinositol 3 kinase contributes to nanoparticle-mediated exaggeration of endotoxin-induced leukocyte procoagulant activity

Nanomedicine (Lond). 2014 Jul;9(9):1311-26. doi: 10.2217/nnm.13.137. Epub 2013 Nov 27.


Aim: Disseminated intravascular coagulation is an increasing concern for certain types of engineered nanomaterials. Recent studies have shed some light on the nanoparticle physicochemical properties contributing to this toxicity; however, the mechanisms are poorly understood. Leukocyte procoagulant activity (PCA) is a key factor contributing to the initiation of this toxicity. We have previously reported on the exaggeration of endotoxin-induced PCA by cationic dendrimers. Herein, we report an effort to discern the mechanism.

Materials & methods: Poly(amidoamine) dendrimers with various sizes and surface functionalities were studied in vitro by the recalcification test, flow cytometry and other relevant assays.

Results & conclusion: Cationic dendrimers exaggerated endotoxin-induced PCA, but their anionic or neutral counterparts did not; the cationic charge prompts this phenomenon, but different cationic surface chemistries do not influence it. Cationic dendrimers and endotoxin differentially affect the PCA complex. The inhibition of phosphoinositol 3 kinase by dendrimers contributes to the exaggeration of the endotoxin-induced PCA.

Keywords: coagulopathy; dendrimer; disseminated intravascular coagulation; leukocyte; nanoparticle; procoagulant activity; thrombosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Blood Coagulation Factors / biosynthesis*
  • Cations / chemistry
  • Cations / toxicity
  • Dendrimers / chemistry
  • Dendrimers / toxicity
  • Disseminated Intravascular Coagulation / etiology
  • Endotoxins / toxicity*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / toxicity
  • Humans
  • In Vitro Techniques
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Lipopolysaccharides / toxicity
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity*
  • Phosphoinositide-3 Kinase Inhibitors*
  • Polyamines / chemistry
  • Polyamines / toxicity


  • Blood Coagulation Factors
  • Cations
  • Dendrimers
  • Endotoxins
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Phosphoinositide-3 Kinase Inhibitors
  • Poly(amidoamine)
  • Polyamines
  • leukocyte procoagulant activity