We describe the synthesis, properties, and application of a new fluorescent potassium chemosensor, KS2, for K+ sensing and imaging in live cells. By virtue of a strong electron-withdrawing group, 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF), with a triazacryptand (TAC) ligand, the new sensor can respond to K+ up to 1.6 M. This is the first highly selective intracellular sensor suitable for sensing K+ over a broad and high concentration range. Confocal fluorescence microscopy has established the utility of KS2 for live-cell K+ detection. Application of KS2 combined with other sensors will be of great benefit for investigating cellular metabolism, detecting and diagnosing diseases including cancer, and monitoring responses to therapy.

A series of new naphthalimide derivatives were synthesized and studied. Three of the materials (SM1, SM2, and SM3) possess methacrylate(s) moieties as pH sensor monomers, enabling these compounds to be polymerized with other monomers for thin film preparation for extracellular pH sensing. Herein, poly(2-hydroxyethyl methacrylate)-co-poly(acrylamide) (PHEMA-co-PAM) was chosen as the polymer matrix. Structure influences on pH responses and pKa values were studied. The film P3 composed of the sensing moiety SM3 has a pKa close to the usual biological environmental pH of ~7. It was used as an extracellular pH sensor to monitor pH change during the metabolism of prokaryotic Escherichia coli (E. coil). On the other hand, the three sensor monomers are new intracellular biomarkers to sense lysosomes of eukaryotic cells since (1) their pKa values are in a range of 5.9 to 6.8; (2) their emission intensities at acidic conditions (such as at pH 5) are much stronger than those at a neutral condition of pH 7; (3) lysosomes range in size from 0.1 to 1.2 μm in diameter with pH ranging from 4.5 to 5.0, which is much more acidic than the pH value of the cytoplasm (usually with a pH value of ~7.2); and (4) the acidity of lysosomes enables a protonation of the amino groups of the pH probes making the sensors emit brightly in acidic organelles by inhibiting the photo-induced electron transfer from the amino groups to the fluorophores. Lysosome sensing was demonstrated using live human brain glioblastoma U87MG cell line, human cervical cancer HeLa cell line, and human esophagus premalignant CP-A and CP-D cell lines by observations of small acidic spherical organelles (lysosomes) and significant colocalizations (82 ~ 95%) of the sensors with a commercially available lysosome-selective staining probe LysoTracker Red® under confocal fluorescence microscopy.

Ratiometric fluorescence sensing is an important technique for precise and quantitative analysis of biological events occurring under complex conditions by simultaneously recording fluorescence intensities at two wavelengths and calculating their ratios. Herein, we design a ratiometric chemosensor for pH that is based on photo-induced electron transfer (PET) and binding-induced modulation of fluorescence resonance energy transfer (FRET) mechanisms. This ratiometric chemosensor was constructed by introduction of a pH-insensitive coumarin fluorophore as a FRET donor into a pH-sensitive amino-naphthalimide derivative as the FRET acceptor. The sensor exhibited clear dual-mission signal changes in blue and green spectral windows upon pH changes. The pH sensor was applied for not only measuring cellular pH, but also for visualizing stimulus-responsive changes of intracellular pH values.

Supramolecular nanomedicines, which use supramolecular design to improve the precision and effectiveness of pharmaceutical practice and optimize pharmacokinetic profiles, have gathered momentum to battle cancer and other incurable diseases, for which traditional small‐molecular and macromolecular drugs are less effective. However, the lack of clinical approval of supramolecular assembly‐based medicine underscores the challenges facing this field. A 2D nanodisc‐based supramolecular structure is formed by a non‐ionic heptamethine cyanine (Cy7) dye, which generates fluorescence self‐quenching but unique photothermal and photoacoustic properties. These Cy7‐based supramolecular nanodiscs exhibit passive tumor‐targeting properties to not only visualize the tumor by near‐infrared fluorescence imaging and photoacoustic tomography but also induce photothermal tumor ablation under irradiation. Due to the nature of organic small molecule, they induce undetectable acute toxicity in mice and can be eliminated by the liver without extrahepatic metabolism. These findings suggest that the self‐assembling cyanine discs represent a new paradigm in drug delivery as single‐component supramolecular nanomedicines that are self‐delivering and self‐formulating, and provide a platform technology for synergistic clinical cancer imaging and therapy.

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