Realizing highly chemoselective detection of H2S in vitro and in vivo with fluorescent probes inside core-shell silica nanoparticles

Hydrogen sulfide (H2S) is an appealing signaling molecule that plays fundamental roles in health and disease. However, H2S-mediated selective chemical transformations for the construction of imaging probes are limited, retarding the interrogation of H2S-related biological processes. Here, we present an alternative approach for engineering a new generation of efficient probes with a nonchemoselective moiety as a building block. To demonstrate our design concept, we developed a sulfoxide-functionalized BODIPY that exhibited a substantial redshift in its absorption and emission spectra upon reduction with H2S. However, such a probe also showed reactivity toward various competing biothiols under aqueous buffer conditions. To achieve high chemoselectivity, we used core-shell silica nanoparticles as an encapsulation matrix to confine the designed molecule probe within their interiors. The inherent molecular-size sieving character of the porous silica shell was capable of impeding competing biothiols from accessing the molecule probe within the core while allowing the specific reaction with the small target H2S. Thus, this strategy avoided disturbance from coexisting biothiols and achieved highly chemoselective detection in ratiometric and near-infrared (NIR) turn-on fluorescence modes. In light of these promising features, together with fast responsiveness and favorable cellular uptake, such a silica nanocomposite was successfully used to detect the endogenous production of H2S in estrogen-induced cardiomyocytes and living mouse model. To our knowledge, the approach reported here is the first to exploit the usefulness of common thiol-sensitive moieties for building chemoselective probes. (C) 2018 Elsevier Ltd. All rights reserved.