Fig. 2.

Nanoparticle protease sensitivity and animal models. (A and B) Fluorescein-functionalized thrombin- or MMP-sensitive (A and B, respectively) NWs were incubated with target enzyme. Proteolytic release of quenched reporters increased fluorescence. Addition of thrombin inhibitor Argatroban (A) or MMP inhibitor Marimastat (B) abrogated fluorescent increase, as did use of d-isomer substrates. (C and D) Induction of thrombosis increased bladder (C) and lung (D) localization of near-infrared fluorophore-labeled thrombin-sensitive NWs over controls. (Scale bar: 5 mm.) (E) Intravenous injection of near-infrared fluorophore-labeled MMP-sensitive NWs resulted in increased bladder localization of reporters in tumor-bearing mice compared with controls. (F) NW mixture administration showed colocalization of blood vessels (CD31; red) and NWs/reporters (fluorescein; green) and significant NW/reporter tumor infiltration. Nuclei were DAPI counterstained (blue). (Scale bar: 50 µm.)