Clotting activity of polyphosphate-functionalized silica nanoparticles

Angew Chem Int Ed Engl. 2015 Mar 23;54(13):4018-22. doi: 10.1002/anie.201409639. Epub 2015 Feb 4.

Abstract

We present a silica nanoparticle (SNP) functionalized with polyphosphate (polyP) that accelerates the natural clotting process of the body. SNPs initiate the contact pathway of the blood-clotting system; short-chain polyP accelerates the common pathway by the rapid formation of thrombin, which enhances the overall blood-clotting system, both by accelerating fibrin generation and by facilitating the regulatory anticoagulation mechanisms essential for hemostasis. Analysis of the clotting properties of bare SNPs, bare polyP, and polyP-functionalized SNPs in plasma demonstrated that the attachment of polyP to SNPs to form polyP-SNPs creates a substantially enhanced synergistic effect that lowers clotting time and increases thrombin production at low concentrations. PolyP-SNP even retains its clotting function at ambient temperature. The polyP-SNP system has the potential to significantly improve trauma-treatment protocols and outcomes in hospital and prehospital settings.

Keywords: hemorrhage; nanoparticles; polyphosphates; silicates; trauma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blood Coagulation / drug effects*
  • Fibrin / chemistry
  • Hemorrhage / drug therapy
  • Hemostasis
  • Magnetic Resonance Spectroscopy
  • Nanoparticles*
  • Particle Size
  • Polyphosphates / chemistry*
  • Silicon Dioxide / pharmacology*
  • Spectrophotometry, Atomic
  • Temperature
  • Thrombin / chemistry
  • Whole Blood Coagulation Time
  • Zirconium / chemistry

Substances

  • Polyphosphates
  • Silicon Dioxide
  • Fibrin
  • Zirconium
  • Thrombin
  • zirconium oxide