Treating non-compressible hemorrhage with functionalized nanoparticles

D. Kudela, A. May-Masnou, C. Nguyen, J.R. Baylis, T. Chuong, C.F. Hebbard, A. Pallaoro, G.B. Braun, S.A. Smith, S. Hammond, L. Ferrigno, C.J. Kastrup, J.H. Morrissey, G.D. Stucky
UCSB, US

Keywords: hemorrhage, nanoparticle, polyphosphate

Summary:

Hemorrhage causes nearly 50% of battlefield deaths. Non-compressible wounds are problematic due to blood loss and coagulopathy. An injectable agent that temporizes such bleeding or reverses coagulopathy would help limit blood loss. We attached short-chain polyphosphate to inorganic silica nanoparticles (SNP-polyP) to enhance coagulation at the injury site. Protecting particles with polyethylene glycol (PEG) limited unwanted clotting. Particles were tested using coagulation analyzers and under flow in microfluidic devices. SNP-polyP lowered clotting time to 1.2 minutes from 2.2 min using lipidated tissue factor (LTF). Under severe hemodilution, clot time fell from 2.35 min (LTF) to 1.35 min (SNP-polyP); under hypothermia clot time fell from 4.17 min (LTF) to 1.53 min (SNP-polyP). Coating SNP-polyP with PEG lengthened clot time to 11.75 min. Under flow, plasma containing SNP-polyP clotted after 40 min at lower shear compared to 200 min at higher shear. Clotting time in pure plasma showed little shear-dependency. Together, SNP-polyP creates a synergistic effect that enhances the body’s natural clotting process to lower clotting time at low concentrations. Nanoparticles loaded with the clotting amplifier polyP and targeted to activate only at sources of bleeding have the potential to serve as a new agent for hemorrhage intervention.