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

Clotting activity of polyphosphate-functionalized silica nanoparticles

Damien Kudela  1 , Stephanie A Smith, Anna May-Masnou, Gary B Braun, Alessia Pallaoro, Chi K Nguyen, Tracy T Chuong, Sara Nownes, Riley Allen, Nicholas R Parker, Hooman H Rashidi, James H Morrissey, Galen D Stucky
Affiliations

Clotting activity of polyphosphate-functionalized silica nanoparticles

Damien Kudela et al. Angew Chem Int Ed Engl. .

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.

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Figures

Figure 1
Figure 1
(Left) TEM images of polyP-SNPs; (Right) 31P NMR spectrum of digested polyP-SNPs shows evidence of phosphorous
Figure 1
Figure 1
(Left) TEM images of polyP-SNPs; (Right) 31P NMR spectrum of digested polyP-SNPs shows evidence of phosphorous
Figure 2
Figure 2
(Top) PolyP-SNP cuts clot time (R value using TEG) roughly in half versus SNP below 0.3 mg/ml. (Bottom) PolyP loaded onto silica lowers clot time compared to bare polyP when measured by fibrometry.
Figure 2
Figure 2
(Top) PolyP-SNP cuts clot time (R value using TEG) roughly in half versus SNP below 0.3 mg/ml. (Bottom) PolyP loaded onto silica lowers clot time compared to bare polyP when measured by fibrometry.
Figure 3
Figure 3
(Top) Thrombin generation is more rapid with polyP-SNP than bare SNP. (Bottom) polyP-SNPs are able to generate a rapid thrombin burst even at low concentrations. Thrombin generation is measured using a thrombin-sensitive fluorescent dye.
Figure 3
Figure 3
(Top) Thrombin generation is more rapid with polyP-SNP than bare SNP. (Bottom) polyP-SNPs are able to generate a rapid thrombin burst even at low concentrations. Thrombin generation is measured using a thrombin-sensitive fluorescent dye.
Figure 4
Figure 4
(Top) Adding PolyP-SNP to LTF shortens clot time in FXII-deficient plasma compared to LTF only or LTF + SNP. LTF required to initiate clotting. (Bottom) PolyP-SNP suspended in aqueous solution retains its procoagulant function after weeks of storage at ambient conditions.
Figure 4
Figure 4
(Top) Adding PolyP-SNP to LTF shortens clot time in FXII-deficient plasma compared to LTF only or LTF + SNP. LTF required to initiate clotting. (Bottom) PolyP-SNP suspended in aqueous solution retains its procoagulant function after weeks of storage at ambient conditions.
Scheme 1
Scheme 1
Simplified coagulation cascadsende. SNP surface induces the activation of FXII, while short-chain polyP enhances the rates of activation of FV and FXI leading to an earlier thrombin burst. Rapid thrombin generation leads to back-activation of FXIa, accelerating the coagulation cascade, as well as facilitating increased activity in the anticoagulation pathway, which is designed to limit the spread of coagulation to uninjured vessels. Kaolin acts only to activate FXII via the intrinsic pathway.
See this image and copyright information in PMC

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