ACS Nano http://doi.org/b8tb(2017)

The plasma protein factor VIII (fVIII) is an essential blood clotting agent that is defective or absent in hemophilia-A patients. Systemic injection of fVIII is used to promote blood coagulation in patients, but in 30% of the cases this strategy fails due to the formation of anti-fVIII antibodies during the treatment.

In their work, Hansen et al. design an alternative strategy for targeted delivery of fVIII, with platelets serving as vehicles for the transport of a fVIII-loaded polyelectrolyte multilayer capsule. The outermost layer of the capsule is composed of fibrinogen for facile hybridization with the platelets. While in other drug delivery approaches an external stimulus induces cargo release, in this case it is the contraction of the platelets, which naturally occurs upon cell activation at the injury site, that triggers release of the drug.

Using a microfluidic vascular injury model and a well plate assay to monitor clotting, the researchers show that their hybridized system shields fVIII from the environment, reducing formation of anti-fVIII antibodies, and demonstrate that the mechanical force created by platelet contraction induces the capsule to burst and deliver the cargo at the injury site. They also measure increased concentration of fibrin, a protein involved in the coagulation process, both in healthy and in fVIII-depleted blood, and reduced blood clotting time, compared with systemic delivery of fVIII.

Finally, while they present their approach as a therapeutic strategy for hemophilia-A, they also suggest that it could be extended to other pathological platelet-mediated conditions such as thrombosis, infections and cancers.