Activation of the coagulation cascade as a mechanism for selective nanoparticle-mediated RNA delivery to the endothelium in vivo

Nanoparticles formulated with certain cationic lipids or polymers have been shown to facilitate RNA delivery to the endothelium. Here, we show that these nanoparticles become coated with coagulating proteins and induce coagulation for RNA delivery in vivo, without leading to histological evidence of clot formation. We further show that nanoparticles previously reported to transfect the liver can be redirected to other organs by preincubating them with procoagulant proteins. Our data demonstrate that activation of the coagulation cascade mediates endothelial RNA delivery and indicate that nanoparticles can be targeted to the endothelium of various organs by integrating procoagulant components in their formulation.