Development of an AIE-active fluorescent probe for the simultaneous detection of Al3+ and viscosity and imaging in Alzheimer's disease model.

Alzheimer's disease is associated both with imbalances in Al3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer's disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer's disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al3+ by fluorescence colormetrics and to viscosity by fluorescence "turn on" modes. Additionally, Al3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al3+ and viscosity.

Near-infrared imaging for visualizing the synergistic relationship between autophagy and NFS1 protein during multidrug resistance using an ICT-TICT integrated platform.

Drug resistance is a major challenge for cancer treatment, and its identification is crucial for medical research. However, since drug resistance is a multi-faceted phenomenon, it is important to simultaneously evaluate multiple target fluctuations. Recently developed fluorescence-based probes that can simultaneously respond to multiple targets offer many advantages for real-time and in situ monitoring of cellular metabolism, including ease of operation, rapid reporting, and their non-invasive nature. As such we developed a dual-response platform (Vis-H2S) with integrated ICT-TICT to image H2S and viscosity in mitochondria, which could simultaneously track fluctuations in cysteine desulfurase (NFS1 protein and H2S inducer) and autophagy during chemotherapy-induced multidrug resistance. This platform could monitor multiple endogenous metabolites and the synergistic relationship between autophagy and NFS1 protein during multidrug resistance induced by chemotherapy. The results indicated that chemotherapeutic drugs simultaneously up-regulate the levels of NFS1 protein and autophagy. It was also found that the NFS1 protein was linked with autophagy, which eventually led to multidrug resistance. As such, this platform could serve as an effective tool for the in-depth exploration of drug resistance mechanisms.

A summary of calixarene-based fluorescent sensors developed during the past five years.

Calixarenes are "chalice like" phenol-based macrocycles that are one of the most fascinating studied scaffolds in supramolecular chemistry. Their preorganized nonpolar cavities and ion binding sites, and their well-defined conformations all lay important foundations for forming host-guest complexes. Conjugation of calixarene scaffolds with various fluorophores at either upper or lower rims has led to the development of smart fluorescent probes for inorganic molecules or ions, aliphatic or aromatic compounds, biomolecules, temperature and hypoxia, even multi-component traditional Chinese medicine (TCM). Moreover, significant advancements have been made for biological applications. This review critically summarizes the recent advances made in these areas.

A novel AIE material for sensing of Erythromycin in pure water by hydrogen bond in portable test strips and cellular imaging applications.

Erythromycin could be used to treat various bacterial infection, but it was harmful to the colonic microflora. Therefore, it is highly desirable to develop a fluorescence probe that could selectively and sensitively detect Erythromycin in pure water. In this work, a fluorescent probe named EHMC, which exhibited aggregation-induced emission (AIE) characteristic in solid state and water/EtOH binary solvent was developed for "turn on" sensing Erythromycin in pure water with high selectivity and sensitivity (detection limit: 1.78 × 10-8 M). Also, there are fewer interference from other antibiotics in the detection process of probe EHMC for Erythromycin. Moreover, probe EHMC could as a portable test strips for highly selective detection of Erythromycin and identification of different concentrations of Erythromycin. In addition, living cells imaging experiments displayed that probe EHMC could detect Erythromycin in A549 cells and BEAS-2B cells successfully. Combined with the theoretical calculation results The sensing mechanisms that the CO in Erythromycin and OH in EHMC formed intermolecular hydrogen bond and further formed new aggregates were confirmed by job' plot, 1H NMR, FT-IR, ESI-MS, DLS and TEM and DFT calculation.

A near-infrared fluorescent probe for in situ imaging of SO2 flux in drug-induced liver injury.

Sulfur dioxide (SO2) has been widely applied as an important additive in various foods and drugs due to its antioxidant, antiseptic and bleaching properties. SO2 in living organisms plays a key biological role as an antioxidant in a variety of life activities. However, abnormal levels of SO2 in both food and living organisms could cause harm and even serious illness, such as diseases related to the respiratory and cardiovascular systems and cancers. Therefore, it is of great practical significance to accurately determine the level of SO2 in food and organisms. In this work, we synthesized a novel near-infrared ratiometric fluorescent probe (NTO) using xanthene and benzopyran as the matrix for the detection of SO2. NTO demonstrates a rapid response (within 8 s), high selectivity, excellent sensitivity (LOD = 3.64 µM) and a long emission wavelength (800 nm), which could be applied to SO2 monitoring in a complex environment. NTO showed a high recovery (90%-110%) of SO2 in food samples such as beer and rock sugar. The results of HeLa cell experiments indicate that NTO has excellent fluorescence labeling ability for SO2 in endoexogenous-sulfide metabolism. In addition, we applied it to mice with acetaminophen (APAP)-induced acute liver injury and observed changes in SO2 during liver injury. Based on these results, we believe that this will provide a convenient visual tool for the detection of the SO2 content in food safety and biomedicine.

Molecular-Dimension-Dependent ESIPT Break for Specific Reversible Response to GSH and Its Real-Time Bioimaging.

Glutathione (GSH) plays many important roles in maintaining intracellular redox homeostasis, and determining its real-time levels in the biological system is essential for the diagnosis, treatment, and pathological research of related diseases. Fluorescence imaging has been regarded as a powerful tool for tracking biomarkers in vivo, for which specificity, reversibility, and fast response are the main issues to ensure the real-time effective detection of analytes. The determination of GSH is often interfered with by other active sulfur species. However, in addition to the common features of nucleophilic addition, GSH is unique in its large molecular scale. 2-(2-Hydroxyphenyl) benzothiazole (HBT) was often formed in the ESIPT process. In this study, HBT was installed with α,ß-unsaturated ketone conjugated coumarin derivates or nitrobenzene, which were used to adjust the reactivity of α,ß-unsaturated ketone. Experimental and theoretical calculations found ESIPT to be favorable in HBT-COU but not HBT-COU-NEt2 or HBT-BEN-NO2 due to the higher electronic energies in the keto form. Thus, for HBT-COU, in the presence of GSH, the hydrogen-bonding interaction between C═N of the HBT unit and carboxyl of GSH would inhibit the process, simultaneously promoting the Michel addition reaction between α,ß-unsaturated ketone and GSH. As a consequence, probe HBT-COU could exhibit a rapid reversible ratiometric response to GSH. Small structures of Hcy and Cys are passivated for such reactions. Cell imaging demonstrated the specific response of the probe to GSH, and the probe was successfully used to monitor fluctuations in GSH concentration during cells apoptosis in real-time.

An ESIPT-induced NIR fluorescent probe to visualize mitochondrial sulfur dioxide during oxidative stress in vivo.

Based on the change in electron distribution of the benzopyrylium unit before and after sulfite addition, a 2-(2'-hydroxyphenyl)benzothiazole (HBT)-based fluorophore generated the excited state intramolecular proton transfer (ESIPT) process with a near-infrared enhanced emission at 836 nm and a large Stokes shift (286 nm). The probe was applied to image SO2 derivatives in cells and mice. Our data will provide new ideas for the development of ESIPT-based fluorescence probe with longer wavelength emission.