Fast tumor imaging using pH-responsive aggregation of cyanine dyes with rapid clearance

Abstract

Rapid and selective tumor detection using conventional pH-activatable chemical probes as contrast agents is challenging. Moreover, a large proportion of the contrast agent is usually retained in the body long-term, which causes potential toxicity risks. In this study, we developed a fluorescent sensor, CypH2S, with a pH-sensitive cyclic substructure for detection of acidic tumor microenvironment. Upon pH variation, the sensor underwent structural changes: the closed-ring form, CypH2S-C, exhibited suppressed dye aggregation, while the open-ring form, CypH2S-O, tended to aggregate in aqueous solutions under slightly acidic conditions. Importantly, CypH2S facilitated rapid and selective tumor visualization in a living mouse model via fluorescence imaging of its pH-responsive aggregation with a 1.9-fold tumor/background ratio (< 1 h). Furthermore, prompt clearance of CypH2S from the bloodstream post-tumor detection occurred because of the relatively small size of the aggregates and cell impermeability. These properties would make CypH2S a promising candidate for clinical tumor diagnosis.