An AIE-Active NIR Fluorescent Probe with Good Water Solubility for the Detection of Aß1-42 Aggregates in Alzheimer's Disease.

Alzheimer's disease (AD), an amyloid-related disease, seriously endangers the health of elderly individuals. According to current research, its main pathogenic factor is the amyloid protein, which is a kind of fibrillar aggregate formed by noncovalent self-assembly of proteins. Based on the characteristics of aggregation-induced emission (AIE), a bislactosyl-decorated tetraphenylethylene (TPE) molecule TMNL (TPE + malononitrile + lactose), bearing two malononitrile substituents, was designed and synthesized in this work. The amphiphilic TMNL could self-assemble into fluorescent organic nanoparticles (FONs) with near-infrared (NIR) fluorescence emission in physiological PBS (phosphate buffered saline), achieving excellent fluorescent enhancement (47-fold) upon its combination with Aß1-42 fibrils. TMNL was successfully applied to image Aß1-42 plaques in the brain tissue of AD transgenic mice, and due to the AIE properties of TMNL, no additional rinsing process was necessary. It is believed that the probe reported in this work should be useful for the sensitive detection and accurate localization mapping of Aß1-42 aggregates related to Alzheimer's disease.

Design and assembly of AIE-active fluorescent organic nanoparticles for anti-counterfeiting fluorescent hydrogels and inks.

Two kinds of AIE-active fluorescent organic nanoparticles were designed and constructed as anti-counterfeiting photoresponsive materials. One is fluorescent organic nanoparticles (TPELs) based on a self-assembly strategy, which were self-assembled from novel amphiphilic tetraphenylethylene (TPE) molecules decorated with a lactose moiety and different photoresponsive tags. The other is polymeric fluorescent organic nanoparticles (F-TPEs) derived from the nanoprecipitation strategy, which utilized pluronic copolymer F127 to encapsulate hydrophobic TPEs without lactosyl modifications. Upon UV light irradiation, these AIE-active materials exhibit different photooxidation behaviors in an aqueous solution to give cyan, orange and green fluorescence emissions, and they were successfully used as an anti-counterfeiting fluorescent hydrogel and ink.

Dual functional amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles for the monitoring and inhibition of insulin amyloid fibrillation based on carbohydrate-protein interactions.

Amyloid-related diseases, such as Alzheimer's disease, are all considered to be related to the deposition of amyloid fibrils in the body. Insulin is a protein hormone that easily undergoes aggregation and fibrillation to form more toxic amyloid-like fibrils. So far, it is still challenging to develop a new protocol to study the ex situ detection and in situ inhibition of amyloid fibrillation. Here, we reported a modular synthetic strategy to construct nine amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles (FONs, TPE2/3/4X, X = G, M or S) with glucosamine (G), mannose (M) or sialic acid (S) as a hydrophilic moiety and tetraphenylethylene (TPE) as a hydrophobic AIE core. The carbohydrate-protein interactions between insulin and TPE2/3/4X were investigated by fluorescence spectroscopy, circular dichroism spectroscopy and transmission electron microscopy. Among the nine FON AIEgens, TPE2G was screened out as the best dual functional FON for the ex situ detection and in situ inhibition of the insulin fibrillation process, indicating that the glycosyl moiety exhibited a crucial effect on the detection/inhibition of insulin fibrillation. The molecular dynamics simulation results showed that the binding mechanism between TPE2G and native insulin was through weak interactions dominated by van der Waals interactions and supplemented by hydrogen bonding interactions to stabilize an α-helix of the insulin A chain, thereby inhibiting the insulin fibrillation process. This work provides a powerful protocol for the further research of amyloid-related diseases based on carbohydrate-protein interactions.

Water-soluble AIE-active fluorescent organic nanoparticles for ratiometric detection of SO2 in the mitochondria of living cells.

We report a water-soluble AIEgen (TYDL) to be self-assembled into fluorescent organic nanoparticles (TYDLs) for specific sensing of SO2 in living hepatoma cells. It is demonstrated that the TYDLs were suitable for ratiometrically detecting endogenous and exogenous SO2 in mitochondria with good selectivity, low detection limit (75 nM) and excellent photostability (>30 min). These findings imply the great potential applications of TYDLs for the diagnosis of SO2-related diseases in cell biology.

Water-soluble Glucosamine-coated AIE-Active Fluorescent Organic Nanoparticles: Design, Synthesis and Assembly for Specific Detection of Heparin Based on Carbohydrate-Carbohydrate Interactions.

Two water-soluble carbohydrate-coated AIE-activate fluorescent organic nanoparticles TPE3G and TPE4G were designed and synthesized for the detection of heparin. Different from the reported strategy, we not only utilized the general detection mechanism of electrostatic interactions, but also introduced the concept of carbohydrate-carbohydrate interactions (CCIs) to enrich the detection mechanism of heparin. TPE3G can serve as an efficient "turn-on" probe with higher selectivity towards heparin than TPE4G. TEM studies revealed that the micro-aggregated TPE3G was encapsulated with the heparin chain to form a complex self-assemblied composite and emits strong fluorescence. It is believed that the results illustrated in this study provide a novel strategy based on CCls to design water-soluble and more efficient bio-probes for various biological and clinical applications.

Water-soluble AIE-Active Fluorescent Organic Nanoparticles: Design, Preparation and Application for Specific Detection of Cysteine over Homocysteine and Glutathione in Living Cells.

Water-soluble ratiometric AIE-active fluorescent organic nanoparticles 2OA-FON for the specific sensing of cysteine over other biothiols are reported. The obtained amphiphilic probe included olefin aldehyde as recognizing unit, tetraphenylethylene as fluorescence reporter and lactose moiety as a hydrophilic group. This work provides a general design strategy based on the introduction of a sugar moiety into a hydrophobic AIEgen to develop ratiometric water-soluble fluorescent organic nanoparticles.