Intravenous
nanoparticle hemostats offer a potentially attractive
approach to promote hemostasis, in particular for inaccessible wounds
such as noncompressible torso hemorrhage (NCTH). In this work, particle
size was tuned over a range of <100–500 nm, and its effect
on nanoparticle–platelet interactions was systematically assessed
using in vitro and in vivo experiments.
Smaller particles bound a larger percentage of platelets per mass
of particle delivered, while larger particles resulted in higher particle
accumulation on a surface of platelets and collagen. Intermediate
particles led to the greatest platelet content in platelet–nanoparticle
aggregates, indicating that they may be able to recruit more platelets
to the wound. In biodistribution studies, smaller and intermediate
nanoparticles exhibited longer circulation lifetimes, while larger
nanoparticles resulted in higher pulmonary accumulation. The particles
were then challenged in a 2 h lethal inferior vena cava (IVC) puncture
model, where intermediate nanoparticles significantly increased both
survival and injury-specific targeting relative to saline and unfunctionalized
particle controls. An increase in survival in the second hour was
likewise observed in the smaller nanoparticles relative to saline
controls, though no significant increase in survival was observed
in the larger nanoparticle size. In conjunction with prior in vitro and in vivo experiments, these
results suggest that platelet content in aggregates and extended nanoparticle
circulation lifetimes are instrumental to enhancing hemostasis. Ultimately,
this study elucidates the role of particle size in platelet–particle
interactions, which can be a useful tool for engineering the performance
of particulate hemostats and improving the design of these materials.