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An excellent agreement for simulated and measured absorption and emission spectra is found for four donor-acceptor aromatic molecules (tetraphenylpyrazine, tetraphenylethene, distirylanthracene and hexaphenylsilole) whose derivatives serve as solid state photosensitizers. After comparing several hybrid TDDFT functionals, EOM-CCSD, and experiments, the best agreement was found with TD-B3LYP and double zeta basis sets (6-31G** and def2-SVP) for one molecule in gas phase. A full characterisation of twelve to twenty electronic excited states was performed in every system. Symmetry-forbidden bands are found in the absorption spectra by sampling a hundred vibrationally geometries from a Wigner distribution. The density of states in the region 2-6 eV was also analysed, showing a very packed region of excited states and suggesting that dark electronic states may play a role in the dynamics of some of the photoexcited systems. Further calculations were done with QM/xTB at geometries extracted from previously published X-ray data to evaluate the influence of the environment on the excitations of the four aggregated molecular crystals.

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Abnormally high levels of copper in tumors stimulate malignant proliferation and migration of cancer cells, which proposes a formidable challenge for the thorough therapy of malignant tumors. In this work, we developed a reliable, mitochondria-targeted near-infrared aggregation-induced emission fluorescent probe, TTQ-Th, whose thiourea moiety specifically could recognize mitochondria even both upon loss of mitochondrial membrane potential or in fixated cells, and can capture copper overexpressed by tumor cells, leading to severe copper deficiency. In parallel, TTQ-Th can generate sufficient reactive oxygen species (ROS) upon photoexcitation, while copper deficiency inhibits expression of related copper-based enzymes, resulting in a decline in ATP production. Such energy deficiency, combined with reduced MMP and elevated oxidative stress can lead to critical cell oncosis. Both in vitro and intracellular experiments can illustrate that the elevated ROS has remarkable damage to tumor cells and contributes to the elimination of the primary tumor, while copper deficiency further hinder tumor cell migration and induces G0/G1 cell cycle arrest in a dose-dependent manner, which is an efficacious strategy for the treatment of malignant tumors.

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A MoS2-based nanotherapeutic platform was developed for synergetic photothermal and photodynamic anti-tumor therapy. AIEgens TFPy-SH molecules were intercalated into MoS2 nanosheets (MoS2 NSs) with S-deficiencies to give the nanocomposite MoS2-TFPy. The AIEgens intercalation expanded the interlayer spacing of MoS2 NSs and induced the transform of MoS2 crystal phase from 2H to 1T, offering MoS2-TFPy nanocomposite high molar absorption coefficient (5.65 L g-1 cm-1), excellent photothermal conversion efficiency under near-infrared (NIR) laser irradiation (38.3%), and favorable intracellular reactive oxygen species (ROS) generation capacity. The positively charged MoS2-TFPy were mainly distributed in mitochondria after cell up-taking, and achieved 1+1>2 anti-tumor effect attributed to its favorable photothermal and photodynamic properties. The high structure and physiological stability, favorable biocompatibility, excellent photothermal and photodynamic therapy effect make the MoS2-TFPy nanoplatform an promising candidate in biomedical clinical applications.

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Aflatoxin B1 (AFB1) contamination in food has attracted worldwide attention. The sensitive detection of AFB1 is vital for ensuring food quality and safety. This study developed an ultrasensitive signal-enhanced lateral flow immunosensor (LFIS) based on the functionalized zirconium metal-organic framework (MOF) of a UiO linker enriched with abundant aggregation-induced emission luminogen (UiOL@AIEgens) probes for the rapid dual-modal point-of-care (POC) determination of AFB1. Using UiO MOFs with numerous active sites as the carrier facilitated abundant AIEgens enrichment on the surface. After coupling with enough anti-AFB1 monoclonal antibodies (mAbs), the green-emissive UiOL@AIEgens-mAbs probes with high specificity and remarkably-enhanced fluorescence responses were obtained to competitively capture target AFB1 in the standard or sample solution and AFB1 antigen immobilized on the test (T) line of the POC LFIS. Under optimum conditions, the LFIS was capable of visual qualitative and smartphone-assisted dual-modal determination of target AFB1 within 7 min. Detection occurred in a range of 0.01-5 ng/mL at an ultra-low detection limit of 0.003 ng/mL, which was 300- and 600-fold lower than traditional immunoassays and the maximum limit set by the European Union, respectively. Moreover, the feasibility and robustness of the LFIS platform were assessed by detecting AFB1 in maize and lotus seed samples with average recoveries of 94.3-109.0%. The developed UiOL@AIEgens-based POC LFIS can be used for ultrasensitive, reliable, on-site detection in food. This study provides a new method for the real-time monitoring of AFB1 and other harmful contaminants in food and more complex matrices.

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A multifunctional nucleoside-based AIEgens sensor (TPEPy-dU) was constructed for visual screening of Hg2+, determine to the reversible response of Fe3+ and biothiols, and applied for cell imaging, and drug-free bacterial killing. The TPEPy-dU displayed 10-folds fluorescence enhancement at 540 nm of emission in response to trace Hg2+ ions with 10 nM of LOD, which can be immediately quenched by adding Fe3+ or GSH/Cys-containing sulfhydryl groups. Moreover, their bacterial staining efficiency closely correlates with their antibacterial efficacy as they demonstrated comparatively higher antibacterial activity against Gram-positive bacteria than Gram-negative bacteria. The drug-free antibacterial results involved the stating prominent surface damages at the sites of interactions between bacterial cells and TPEPy-dU that were further verified by CLSM and SEM images. It can be applied as a potential fluorescent agent to explore the related antibacterial mechanisms for treating and monitoring bacterial infections in vivo due to their nontoxic nature. Compared with conventional sensors and antibacterial therapies, these findings elevated the synthetic strategies of fluorescent probes and represented an advanced antibacterial agent wearing quaternary ammonium cationic with low resistance in clinical diagnosis.

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Lipid droplets (LDs) targeting probes are important for investigating the biological functions of LDs. The interplay between LDs and some other organelles can help to further understand the biological functions of these organelles. However, it is still a challenge to design functional probes that can specifically target LDs and are responsive to some other organelles. Herein, a multifunctional aggregation-induced emission luminogen (AIEgen), namely the TPA-CN, was prepared by the simple aldimine condensation reaction for lipid droplet-specific imaging and tracing. TPA-CN can be sensitively responsive to the acid environment of lysosomes due to the pH-response detachable connector in TPA-CN. With the assistance of this characteristic, it can be concluded from the fluorescence imaging and co-localization analysis results that the internalization of TPA-CN and the targeting of LDs does not involve the lysosome and the lysosomal escape process. At last, the TPA-CN was successfully used for the high-sensitivity imaging of dynamic information of LDs.

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AIEgens have emerged as a promising alternative to molecular rotors in bioimaging applications. However, transferring the concept of aggregation-induced emission (AIE) from solution to living systems remains a challenge. Given the highly heterogeneous nature and the compartmentalization of the cell, different approaches are needed to control the self-assembly within the crowded intricate cellular environment. Herein, we report for the first time the self-assembly mechanism of an anthracene-guanidine derivative (AG) forming the rare and highly emissive T-shaped dimer in breast cancer cell lines as a proof of concept. This process is highly sensitive to the local environment in terms of polarity, viscosity, and/or water quantity that should enable the use of the AG as a fluorescence lifetime imaging biosensor for intracellular imaging of cellular structures and the monitoring of intracellular state parameters. Different populations of the monomer and T-shaped and π-π dimers were observed in the cell membrane, cytoplasm, and nucleoplasm, related to the local viscosity and presence of water. The T-shaped dimer is formed preferentially in the nucleus because of the higher density and viscosity compared to the cytoplasm. The present results should serve as a precursor for the development of new design strategies for molecular systems for a wide range of applications such as cell viscosity, density, or temperature sensing and imaging.

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In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor­ and mitochondria­targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.

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Organelles are the working hubs of the cells. Hence, visualizing these organelles inside the cells is highly important for understanding their roles in pathological states and development of therapeutic strategies. Herein, we report the development of a novel highly substituted oxazoles with modular scaffolds (AIE-ER, AIE-Mito, and AIE-Lyso), which can home into endoplasmic reticulum (ER), mitochondria, and lysosomes inside the cells. These oxazoles showed remarkable aggregation-induced emission (AIE) property in water and in the solid state due to dual intramolecular H-bonding, which was confirmed by pH- and temperature-dependent fluorescence studies followed by molecular dynamics (MD) simulations and density functional theory (DFT) calculations. Confocal laser scanning microscopy studies revealed that AIE-ER, AIE-Mito, and AIE-Lyso efficiently homed into ER, mitochondria and lysosomes, respectively, in the HeLa cervical cancer cells and non-cancerous human retinal pigment epithelial RPE-1 cells within 3 h without showing any toxicity to the cells with high sub-cellular photostability. To the best of our knowledge, this is the first report of highly substituted oxazole-based small molecule AIEgens for organelle imaging. We anticipate these novel AIEgens have promise to image sub-cellular organelles in different diseased states as well as understanding the inter-organelle interactions towards the development of novel therapeutics.

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Hg2+ contamination in sewage can accumulate in the human body through the food chains and cause health problems. Herein, a novel aggregation-induced emission luminogen (AIEgen)-encapsulated hydrogel probe for ultrasensitive detection of Hg2+ was developed by integrating hydrophobic AIEgens into hydrophilic hydrogels. The working mechanism of the multi-fluorophore AIEgens (TPE-RB) is based on the dark through-bond energy transfer strategy, by which the energy of the dark tetraphenylethene (TPE) derivative is completely transferred to the rhodamine-B derivative (RB), thus resulting in intense photoluminescent intensity. The spatial networks of the supporting hydrogels further provide fixing sites for the hydrophobic AIEgens to enlarge accessible reaction surface for hydrosoluble Hg2+, as well create a confined reaction space to facilitate the interaction between the AIEgens and the Hg2+. In addition, the abundant hydrogen bonds of hydrogels further promote the Hg2+ adsorption, which significantly improves the sensitivity. The integrated TPE-RB-encapsulated hydrogels (TR hydrogels) present excellent specificity, accuracy and precision in Hg2+ detection in real-world water samples, with a 4-fold higher sensitivity compared to that of pure AIEgen probes. The as-developed TR hydrogel-based chemosensor holds promising potential as a robust, fast and effective bifunctional platform for the sensitive detection of Hg2+.

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Sialic acid (SA) is an acidic monosaccharide present in the human brain and body fluids in the form of N-acetylneuraminic acid. It is also a well-known cancer biomarker. For decades, it has remained a challenging task to design synthetic receptors for SA. However, mainly because of the interference from other sugars with the receptors, it was challenging to differentiate SA from other sugars. Here, we report the development of a two-component aggregation-induced emissive (AIE) probes that can interact with SA and other saccharides via noncovalent interactions with unique emission fingerprints. Analysis of the output signals enabled the reliable detection and clear discrimination of SA in the presence of other saccharides with high accuracy. Further, its potential application in cellular glycan mapping has been explored by fluorescence imaging and surface-enhanced Raman scattering with MDA-MB-231 breast cancer cells.

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Aggregation-induced emission (AIE) is a unique photophysical process, and its emergence brings a revolutionary change in luminescence. However, AIE-based research has been limited to a few classical molecular skeletons, which is unfavorable for in-depth studies of the photophysical characteristics of AIE and the full exploitation of their potential values. There is an urgent need to develop new skeletons to rise to the challenges of an insufficient number of AIE core structures and difficult modification. Here, we report a novel dumbbell AIE skeleton, in which two phenyls are connected through (E)-3-iminoprop-1-en-1-amine. This skeleton shows extremely strong solid-state emission with an absolute quantum yield up to 69.5%, a large Stokes shift, and typical AIE characteristics, which well resolves the challenge of difficult modification and low luminous efficiency of the traditional AIE skeletons. One-step reaction, high yield, and diversified modification endow the skeleton with great scalability from simple to complicated, or from symmetrical to asymmetrical structures, which establishes the applicability of the skeleton in various scenarios. These molecules self-assemble into highly ordered layer-, rod-, petal-, hollow pipe-, or helix-like nanostructures, which contribute to strong AIE emission. Crystallographic data reveal the highly ordered layer structures of the aggregates with different substituents, and a novel halogen bond-driven self-assembly mechanism that restricts intramolecular motion is clearly discovered. Taking advantage of these merits, a full-band emission system from green to red is successfully established, which displays great potential in the construction of light-emitting films and advanced light-emitting diodes. The discovery of this AIE skeleton may motivate a huge potential application value in luminescent materials and lead to hitherto impossible technological innovations.

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Early detection of metallic corrosion is one considerable method to reduce imperceptible disasters nowadays. Fluorescent coatings with high sensitivity and long lifetimes for use in the early detection of metallic corrosion are in high demand, but they are presently difficult to prepare. Inspired by the chameleon's skin, which is capable of switching its color in different atmospheres sensitively and reversibly, we proposed herein a facile and universal all-in-one strategy of combining the fluorescent sensitivity and dynamic hydrogen bonds in a hydrogel to develop a reusable corrosion detection tape to cover metal surfaces. The fluorescent hydrogel tape was constructed using free radical copolymerization of monomers [hydroxyethyl methylacrylate (HEMA) and tetraphenylethene derivatives (TPEPy)]. Due to the aggregation-induced emission (AIE) behavior of TPEPy, the poly(HEMA-co-TPEPy) hydrogel is capable of monitoring the traces of corrosion via the release of ferric ions with a concentration as low as 10-5 M. Moreover, due to the dynamic hydrogen bonds of hydroxyethyl groups in hydrogel networks, the fluorescent hydrogel tape exhibited good adhesion and well reusability for over 10 applications to effectively warn against early corrosion of stainless steel. This non-destructive and reversible method of early corrosion detection can provide valuable signals when maintenance is needed before the metal suffers serious damage.

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Advances in the development of aggregation-induced emission luminogens (AIEgens) depend on understanding how the molecular packing affects their luminescent properties and on making nanoparticles (NPs) with desired sizes. Although reported strategies have advanced the field, rational control of molecular packing and efficient fabrication of AIEgen NPs sub-5.5 nm in diameter remain pressing issues. Here we report a "freeze assembly" strategy, in which the diameter of AIEgen NPs can be precisely tuned from ∼3 nm to hundreds of nanometers, and a molecular packing in kinetically trapped states that are not easily captured by conventional assembly methods can be obtained, leading to tunable fluorescence emissions. Therefore, this study provides a significant tool to fabricate organic luminescent nanomaterials with diameters smaller than 5 nm, which is of critical importance for biomedical applications; meanwhile, tuning molecular packing in nanoparticles displaying different fluorescence may help to shed new light on the mechanism of AIEgens.

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The complex environment of solid tumors and the migration of cancer cells are important obstacles to the cure of tumors through conventional therapy. Developing secure and efficient photosensitizers (PSs) is the crux to the application of photodynamic therapy (PDT) in the noninvasive clinical treatment of tumors. Herein, a series of PSs (DCTPys) with the same skeleton structure was designed and prepared. The unique molecular structure of DCTPys endows them with aggregation-induced emission (AIE) property and efficient reactive oxygen species (ROS) generation ability. Interestingly, due to their hydrophilic and lipophilic nature, DCTPys have fine staining and visual identification performance for the plasma membrane. In addition (e.g., MeDCTPy-OH), ROS is produced by MeDCTPy-OH under white light irradiation, which could destroy the completeness of cell membranes and cause cell necrosis. Importantly, morphology imaging of the cell membrane using MeDCTPy-OH enables real-time tracking of cancer cell ablation. This allowed cell necrosis and PDT effects to be observed under mild conditions. We conclude that DCTPys are potential cell membrane-selective PSs for PDT, and it is worth systematically exploring the phototherapeutic effect of these PSs on tumors in vivo.

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Insulin, the only hormone regulating blood glucose level, is strongly associated with diabetes and its complications. Specific recognition and ultrasensitive detection of insulin are of clinical significance for the early diagnosis and treatment of diabetes. Inspired by aggregation-induced emission, we presented a turn-on label-free fluorescence aptasensor for insulin detection. Quaternized tetraphenylethene salt was synthesized as the fluorescence probe. Guanine-rich aptamer IGA3 was selected as recognition element. Graphene oxide was chosen as the quencher. Under optimized conditions, the fluorescence aptasensor displayed a wide linear range (1.0 pM-1.0 µM) with a low limit of detection (0.42 pM). Furthermore, the aptasensor was successfully applied to detect insulin in human serum. Spiked recoveries were obtained in the range of 96.06%-104.26%. All these results demonstrated that the proposed approach has potential application in the clinical diagnostics of diabetes.

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Luminogens with aggregation-induced emission (AIEgens) properties have numerous broad applications in fields of chemical and biological analyses due to their exceptional photostability, excellent signal reliability, high quantum yield, and large Stokes' shift. In particular, AIEgens also bring new blood for immunoassay. Since publication of the first 2004 paper, AIEgens-based immunoassays have received significant attention because of their high sensitivity, specificity, accuracy, and reliability. However, until now, there have been no comprehensive literature reviews focused on the evolving field of AIEgens-based immunoassays. Thus, we have extensively reviewed AIEgens-based immunoassays from their basic working principles to specific applications. We focus on several fundamental elements of AIEgens-based immunoassays, including the typical structures of AIEgens, emission mechanism of AIEgens probes, function of AIEgens in immunoassays, and platform of AIEgens-based immunoassays. Then, the representative applications of AIEgens-based immunoassays in food safety, medical diagnostics, and environmental monitoring are explored. Thus, proposals on how to further improve the AIEgens-based immunoassay performance are also discussed, as well as future challenges and perspectives, aiming to provide brief and valid guidelines for choosing suitable AIEgens-based immunoassays according to specific application requirements.

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Real-time intraoperative guidance is essential during various surgical treatment of many diseases. Aggregation-induced emission (AIE) materials have shown great potential for guiding surgeons during complex interventions, with the merits of deep tissue penetration, high quantum yield, high molar absorptivity, low background, good targeting ability and excellent photostability. Herein, we provided insights to design efficient AIE materials regarding three key parameters, i.e., deep-tissue penetration ability, high brightness of AIE luminogens (AIEgens), and precise tumor/other pathology nidus targeting strategies, for realizing better application of fluorescence image-guided surgery. Representative interdisciplinary achievements were outlined for the demonstration of this emerging field. Challenges and future opportunities of AIE materials were briefly discussed. The aim of this review is to provide a comprehensive view of AIE materials for intraoperative guidance for researchers and surgeons, and to inspire more further correlational studies in the new frontiers of image-guided surgery.

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Aggregation-induced emission luminogens (AIEgens) possess enhanced fluorescence in highly aggregated states, thus enabling AIEgens as a promising module for highly emissive fluorescence biomaterials. So far, AIEgens-based nanomaterials and their hybrids have been reported for biomedical applications. Benefiting from the intrinsic biocompatibility and biofunction-editing properties of peptides, peptide-AIEgens hybrid biomaterials reveal unlimited possibilities including target capacity, specificity, stimuli-responsiveness, self-assembly, controllable structural transformation, etc.. In the last two decades, peptide-AIEgens hybrid nanomaterials with a unique design concept in aggregated states have achieved various biomedical applications such as biosensing, bioimaging, imaging-guided surgery, drug delivery and therapy. More recently, programmable design of peptide-AIEgens for in situ self-assembly provides a unique strategy for constructing intelligent entities with defined biological functions. In this review, we summarize the basic design principle of programmable peptide-AIEgens, structure-effect relationship and their unusual biomedical effects. Finally, an outlook and perspective toward future challenges and developments of peptide-AIEgens nanomaterials are concluded.