Aggregation Enhanced Responsiveness of Rationally Designed Probes to Hydrogen Sulfide for Targeted Cancer Imaging.

Activatable molecular probes hold great promise for targeted cancer imaging. However, the hydrophobic nature of most conventional probes makes them generate precipitated agglomerate in aqueous media, thereby annihilating their responsiveness to analytes and precluding their practical applications for bioimaging. This study reports the development of two small molecular probes with unprecedented aggregation enhanced responsiveness to H2S for in vivo imaging of H2S-rich cancers. The subtle modulation of the equilibrium between hydrophilicity and lipophilicity by N-methylpyridinium endows these designed probes with the capability of spontaneously self-assembling into nanoprobes under physiological conditions. Such probes in an aggregated state, rather than a molecular dissolved state, show NIR fluorescence light up and photoacoustic signals turn on upon H2S specific activation, allowing in vivo visualization and differentiation of cancers based on differences in H2S content. Thus, our study presents an effective design strategy which should pave the way to molecular design of optimized probes for precision cancer diagnostics.