Thrombin activatable NIRF/CT multimodal imaging probe based on gold nanoparticls

Abstract

Gold nanoparticle (AuNP) is a well-known biocompatible material with advantages of controllable interfacial properties, low cytotoxicity, and high X-ray absorption. AuNPs have been applied to biomedical fields including drug delivery, gene delivery and molecular imaging probe. In this study, we developed thrombin activatable CT/NIRF multimodal imaging probe and visualized thrombosis in carotid artery stream. AuNPs were coated with poly(ethylene glycol) (PEG) and silica for enhanced biocompatibility in physiological condition. The size of the core shell imaging probe was 118±22 nm by DLS, silica shell was 8.3±0.9 nm by analyzing with TEM. Silica shell surface was further modified with thrombin activatable peptide-NIRF dyes. AuNPs have advantages as compared with other nanoparticles based on the broad absorption spectrum which induces fluorescence quenching of the dye. At normal state NIRF dye conjugated to the imaging probe was quenched due to nanoparticle surface energy transfer (NSET) between AuNP and dyes which were located less than 10 nm distance from the surface. On the contrary, thrombin expressed near thrombus stimulated degradation of the connecting peptide and freed dyes beyond the quenching distance. Protease-specific degradation recovered the fluorescence and optically visualized the thrombus. Micro CT was used to measure the feasibility of the developed probe as a CT contrast agent. For in vivo experiments, C57BL/6 mice were used as an animal model. Thrombus was formed in left distal common carotid artery (CCA). After Intravenous injection of the imaging probe, thrombosis was simultaneously detected using NIRF/CT imaging modalities, which provided CT images with high spatial resolution and optical images with disease-site selectivity. In conclusion, we developed CT/NIRF multimodal imaging probe by decorating the surface AuNP with PEG, silica and thrombin-activatable fluorescent dyes. In vitro and in vivo experiments proved the feasibility of biocompatible imaging probe with promising results for detecting thrombosis