Tissue factor is an upstream component of the cascade and a high-expressing factor under phathological conditions. In this study, a tissue factor cascade-targeted strategy for inducing local thrombosis was developed by combining ENP-HMME and photochemistry. In vitro study showed that protein EGFP-EGF1 conjugation to the nanoparticles could significantly contribute to the uptake of nanoparticles by tissue factor over-expressed brain capillary endothelial cells. Three-dimensional imaging and specklegram of brains in vivo showed that tissue factor cascade-targeted strategy successfully induced thrombosis of expected position. As shown by the in vivo multispectral fluorescent imaging, when ENP-HMME was combined with photochemistry, higher accumulation in the infarction hemisphere was observed, which might suggest that the photochemistry inducing tissue factor cascade recruited more ENP-HMME than HMME-loaded nanoparticles (NP-HMME). The data indicated the tissue factor cascade-targeted strategy has potential to induce local thrombosis, and might be applied in the treatment of a variety of hypervascular diseases.
Keywords: EGFP-EGF1 protein; HMME; Tissue factor; nanoparticles; photochemistry; thrombosis.