Activity-Based Sensing and Theranostic Probes Based on Photoinduced Electron Transfer.

Abstract

Fluorescent probes have become powerful tools in detection, imaging and disease diagnosis due to their high sensitivity, specificity, fast response, and technical simplicity. In the last decades, researchers have made remarkable progress in developing signaling mechanisms to design fluorescent probes such as photoinduced electron transfer (PET), intramolecular charge transfer (ICT), and fluorescence resonance energy transfer (FRET). Typical PET is composed of a multicomponent system in which a fluorophore (electron acceptor) is separately linked with a recognition group (electron donor) via a short spacer. PET probes normally feature a low fluorescence background and significant fluorescence enhancement in response to targets. Recent research revealed that PET probes have also been used as theranostic agents, whose fluorescence and toxicity can be simultaneously activated by cancer-specific parameters. In this Account, we highlight the recent advances of rational design and applications of PET probes, focusing primarily on studies from our research group. For example, different from the case of the traditional single-atom electron donor (O, S, N, Se, Te, etc.) in typical PET, we used more a electron-rich pyrrole ring to "switch off" the fluorescence of the fluorophore more efficiently through an "enhanced PET" effect which provided a lower background fluorescence and higher signal-to-noise ratio. Furthermore, normal PET represents the main principle behind the design of small molecule "off-on" fluorescent sensors. We developed new PET platform through intramolecular space folding (folding PET) to overcome the difficulty of designing PET enzyme-targeting probes. Therefore, based on typical PET and these new PET concepts, we, for instance, reported PET probes for the detection of Zn2+ without proton interference, a BODIPY-based d-PET probe for reporting local hydrophilicity within lysosomes, and an "enhanced PET" fluorescent probe for imaging HClO in cancer cells. We also developed COX-2-specific probe for identifying cancer cells and quantifying cancer-related events, and a KIAA1363-sensitive probe for tracking solid tumors in living mice. Furthermore, we first applied an aminopeptidase N (APN)-sensitive probe based on PET for cancer diagnosis and therapy. We anticipate that further development of PET fluorescent probes providing more sensitivity and selectivity to analytes of interest will be equipped with more functions and play indispensable roles in the studies of pathology, diagnostics, and cancer therapies.