Discovery of Imaging and Therapeutic Integration Bifunctional Molecules Based on Bio-Orthogonal Reaction and Releasable Disulfide Bond

The application of conventional fluorescent probes in living cells has been limited by excess fluorescence interference, reduced selectivity, and poor permeability. Herein, we describe a convenient solution for overcoming the above limitations based on bio-orthogonal reactions and releasable linkers that provide bifunctional molecules for imaging and therapeutic integration. To reduce the interference of excess fluorescent moieties, a bio-orthogonal reaction was applied to activate the fluorescence of the active parent drugs without fluorophores. Moreover, disulfide bonds were incorporated as releasable linkers. After imaging the target protein, the newly yielded fluorophore could be released from the active drugs based on the highly reducing conditions of the tumor. Thus, these bifunctional molecules are comparable in therapeutic activity to the parent drug. These novel imaging and therapeutic integration molecules could be used to realize imaging-aided diagnosis and perform efficient real-time monitoring of cancer cells. Our findings are expected to enable efficient and specific imaging and real-time in vivo prognostic monitoring in the clinic.