The development of logic gate-based fluorescent probes that respond to intracellular hydrogen peroxide and pH in tandem.

Logic gate-based fluorescent probes are powerful tools for the discriminative sensing of multiple signaling molecules that are expressed in concert during the progression of many diseases such as inflammation, cancer, aging, and other disorders. To achieve logical sensing, multiple functional groups are introduced to the different substitution sites of a single fluorescent dye, which increases the complexity of chemical synthesis. Herein, we report a simple strategy that incorporates just one responsive unit into a hemicyanine dye achieving the logic gate-based sensing of two independent analytes. We introduce boronic acid to hemicyanine to quench the fluorescence, and in the presence of hydrogen peroxide (H2O2), the fluorescence is recovered due to removal of the boronate. Interestingly, the subsequent decrease in pH turned the red fluorescence of hemicyanine to green emissive because of protonation of the phenolic alcohol. This unique feature of the probe enables us to construct "INHIBIT" and "AND" logical gates for the accurate measuring of intracellular H2O2 and acidic pH in tandem. This study offers insight into the simple construction of logic-gate based fluorescent probes for the tandem sensing of multiple analytes that are correlatively produced during disease progression.

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor.

The development of photochromic fluorescence sensors with dynamic and multiple-signaling is beneficial to the improvement of biosensing/imaging precision. However, elaborate designs with complicated molecular structures are always required to integrate these functions into one molecule. By taking advantages of both redox-active/high loading features of two-dimensional (2D) manganese dioxide (MnO2) and dynamic fluorescence photoswitching of photochromic sensors, we here design a hybrid photochromic MnO2 glycosheet (Glyco-DTE@MnO 2 ) to achieve the photoswitchable imaging of intracellular glutathione (GSH). The photochromic glycosheet manifests significantly turn-on fluorescence and dynamic ON/OFF fluorescence signals in response to GSH, which makes it favorable for intracellular GSH double-check in targeted human hepatoma cell line (HepG2) through the recognition between ß-D-galactoside and asialoglycoprotein receptor (ASGPr) on cell membranes. The dynamic fluorescence signals and excellent selectivity for detection and imaging of GSH ensure the precise determination of cell states, promoting its potential applications in future disease diagnosis and therapy.

Fluorogenic probes for disease-relevant enzymes.

Traditional biochemical methods for enzyme detection are mainly based on antibody-based immunoassays, which lack the ability to monitor the spatiotemporal distribution and, in particular, the in situ activity of enzymes in live cells and in vivo. In this review, we comprehensively summarize recent progress that has been made in the development of small-molecule as well as material-based fluorogenic probes for sensitive detection of the activities of enzymes that are related to a number of human diseases. The principles utilized to design these probes as well as their applications are reviewed. Specific attention is given to fluorogenic probes that have been developed for analysis of the activities of enzymes including oxidases and reductases, those that act on biomacromolecules including DNAs, proteins/peptides/amino acids, carbohydrates and lipids, and those that are responsible for translational modifications. We envision that this review will serve as an ideal reference for practitioners as well as beginners in relevant research fields.