Reversing Coagulopathy and Internal Hemorrhage with Functionalized Nanoparticles

D. Kudela, A. May-Masnou, S.A. Smith, G. Braun, A. Pallaoro, T. Chuong, J.H. Morrissey, G.D. Stucky
University of Californi, Santa Barbara, US

Keywords: nanomedicine, drug delivery, silica nanoparticles, internal hemorrhage control, hemorrhage, coagulopathy, polyphosphate

Summary:

Uncontrolled hemorrhage is a major cause of preventable death. Wound treatment focuses on using nanostructured oxide and clay-based materials to quicken clot formation. Internal injuries further complicate treatment due to inaccessibility. In response to severe trauma, the body can develop coagulopathy - the fundamental breakdown of the coagulation cascade. To rectify this situation, we developed a polyphosphate functionalized silica nanoparticle (SNP-P70) agent for hemorrhage intervention that 1) promotes coagulation under coagulopathic conditions and 2) can be protected to selectively target internal injuries. The silica nanoparticle (SNP) acts by activating FXII and the contact activation pathway; ~ 70 monomer length polyphosphate (P70) increases concentration of FVa. When combined, SNP-P70 performs a synergistic effect that outperforms known procoagulants such as bare silica, polyphosphate, and lipidated tissue factor even upon extreme hemodilution and hypothermia. To heal internal hemorrhage, the SNP-P70 is coated with PEG to avoid unwanted clotting in healthy vessels. In damaged vessels, the SNP-P70 specifically targets wounds to activate and prevent further blood loss. The success of SNP-P70 under severe trauma suggests future viability as a nano therapeutic for both external and internal hemorrhage, and coagulopathy.