Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo.

Bacteria infected cells acting as "Trojan horses" not only protect bacteria from antibiotic therapies and immune clearance, but also increase the dissemination of pathogens from the initial sites of infection. Antibiotics are hard and insufficient to treat such hidden internalized bacteria, especially multidrug-resistant (MDR) bacteria. Herein, aggregation-induced emission luminogens (AIEgens) such as N,N-diphenyl-4-(7-(pyridin-4-yl) benzo [c] [1,2,5] thiadiazol-4-yl) aniline functionalized with 1-bromoethane (TBP-1) and (3-bromopropyl) trimethylammonium bromide (TBP-2) (TBPs) show potent broad-spectrum bactericidal activity against both extracellular and internalized Gram-positive pathogens. TBPs trigger reactive oxygen species (ROS)-mediated membrane damage to kill bacteria, regardless of light irradiation. TBPs effectively kill bacteria without the development of resistance. Additionally, such AIEgens activate mitochondria dependent autophagy to eliminate internalized bacteria in host cells. Compared to the routinely used vancomycin in clinic, TBPs demonstrate comparable efficacy against methicillin-resistant Staphylococcus aureus (MRSA) in vivo. The studies suggest that AIEgens are promising new agents for the treatment of MDR bacteria associated infections.

A lipophilic AIEgen for lipid droplet imaging and evaluation of the efficacy of HIF-1 targeting drugs.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates the cellular response to hypoxia. The upregulation of HIF-1 expression in hypoxic cells can induce the accumulation of lipid droplets (LDs), and the LD levels can in turn reflect the expression level of HIF-1. Herein, we report a LD-specific luminogen with aggregation-induced emission characteristics (AIEgen), and have explored its potential applications in the evaluation of the inhibitory efficacy of HIF-1 targeting drugs. Compared to Nile red, this AIEgen shows a larger Stokes shift, better photostability, a more sensitive response to changes in dye concentration and a broader quantitative range. We found that the AIEgen can be used for semi-quantifying LD levels in cancer cells under hypoxic conditions, and for evaluating the inhibitory efficacy of HIF-1 targeting drugs. This work provides a simple and cost-effective strategy for screening HIF-1-targeted drugs, which may also be an alternative for evaluating the drug efficacy of other LD-related diseases.

In vivo monitoring of tissue regeneration using a ratiometric lysosomal AIE probe.

Tissue regeneration is a crucial self-renewal capability involving many complex biological processes. Although transgenic techniques and fluorescence immunohistochemical staining have promoted our understanding of tissue regeneration, simultaneous quantification and visualization of tissue regeneration processes is not easy to achieve. Herein, we developed a simple and quantitative method for the real-time and non-invasive observation of the process of tissue regeneration. The synthesized ratiometric aggregation-induced-emission (AIE) probe exhibits high selectivity and reversibility for pH responses, good ability to map lysosomal pH both in vitro and in vivo, good biocompatibility and excellent photostability. The caudal fin regeneration of a fish model (medaka larvae) was monitored by tracking the lysosomal pH change. It was found that the mean lysosomal pH is reduced during 24-48 hpa to promote the autophagic activity for cell debris degradation. Our research can quantify the changes in mean lysosomal pH and also exhibit its distribution during the caudal fin regeneration. We believe that the AIE-active lysosomal pH probe can also be potentially used for long-term tracking of various lysosome-involved biological processes, such as tracking the stress responses of tissue, tracking the inflammatory responses, and so on.

A facile strategy for realizing room temperature phosphorescence and single molecule white light emission.

Research on materials with pure organic room temperature phosphorescence (RTP) and their application as organic single-molecule white light emitters is a hot area and relies on the design of highly efficient pure organic RTP luminogens. Herein, a facile strategy of heavy-atom-participated anion-π+ interactions is proposed to construct RTP-active organic salt compounds (1,2,3,4-tetraphenyloxazoliums with different counterions). Those compounds with heavy-atom counterions (bromide and iodide ions) exhibit outstanding RTP due to the external heavy atom effect via anion-π+ interactions, evidently supported by the single-crystal X-ray diffraction analysis and theoretical calculation. Their single-molecule white light emission is realized by tuning the degree of crystallization. Such white light emission also performs well in polymer matrices and their use in 3D printing is demonstrated by white light lampshades.

Aggregation-Induced Emission Probe for Specific Turn-On Quantification of Soluble Transferrin Receptor: An Important Disease Marker for Iron Deficiency Anemia and Kidney Diseases.

Transferrin receptor (TfR) is overexpressed on the surface of many cancer cells due to its vital roles in iron circulation and cellular respiration. Soluble transferrin receptor (sTfR), a truncated extracellular form of TfR in serum, is an important marker of iron deficiency anemia (IDA) and bone marrow failure in cancer patients. More recently, sTfR level in urine has been related to a specific kidney disease of Henoch-Schönlein purpura nephritis (HSPN). Despite the universal significance of sTfR, there is still a lack of a simple and sensitive method for the quantification of sTfR. Furthermore, it is desirable to have a probe that can detect both TfR and sTfR for further comparison study. In this work, we developed a water-soluble AIE-peptide conjugate with aggregation-induced emission (AIE) characteristics. Taking advantage of the negligible emission from molecularly dissolved tetraphenylethene (TPE), probe TPE-2T7 was used for the light-up detection of sTfR. The probe itself is nonemissive in aqueous solution, but it turns on its fluorescence upon interaction with sTfR to yield a detection limit of 0.27 µg/mL, which is much lower than the sTfR level in IDA patients. Furthermore, a proof-of-concept experiment validates the potential of the probe for diagnosis of HSPN by urine test.

Activatable Fluorescent Nanoprobe with Aggregation-Induced Emission Characteristics for Selective In Vivo Imaging of Elevated Peroxynitrite Generation.

An activatable fluorescent nanoprobe with aggregation-induced emission signature is developed. The nanoprobe is nonfluorescent, but can be induced to emit intensely after reaction with peroxynitrite forming an intramolecular hydrogen bond. Excellent performance for selective in vivo imaging of inflammation with elevated peroxynitrite generation and efficient visualization of in vivo treatment efficacy of anti-inflammatory agents is demonstrated.