Aggregation‐Induced Emission Gold Clustoluminogens for Enhanced Low‐Dose X‐ray‐Induced Photodynamic Therapy

The use of gold nanoparticles as radiosensitizers is an effective way to boost the killing efficacy of radiotherapy while drastically limiting the received dose and reducing the possible damage to normal tissues. Herein, we designed aggregation‐induced emission gold clustoluminogens (AIE‐Au) to achieve efficient low‐dose X‐ray‐induced photodynamic therapy (X‐PDT) with negligible side effects. The aggregates of glutathione‐protected gold clusters (GCs) assembled through a cationic polymer enhanced the X‐ray‐excited luminescence by 5.2‐fold. Under low‐dose X‐ray irradiation, AIE‐Au strongly absorbed X‐rays and efficiently generated hydroxyl radicals, which enhanced the radiotherapy effect. Additionally, X‐ray‐induced luminescence excited the conjugated photosensitizers, resulting in a PDT effect. The in vitro and in vivo experiments demonstrated that AIE‐Au effectively triggered the generation of reactive oxygen species with an order‐of‐magnitude reduction in the X‐ray dose, enabling highly effective cancer treatment.     

Mitochondria‐Targeted Cancer Therapy Using a Light‐Up Probe with Aggregation‐Induced‐Emission Characteristics

Subcellular organelle‐specific reagents for simultaneous tumor targeting, imaging, and treatment are of enormous interest in cancer therapy. Herein, we present a mitochondria‐targeting probe (AIE‐mito‐TPP) by conjugating a triphenylphosphine (TPP) with a fluorogen which can undergo aggregation‐induced emission (AIE). Owing to the more negative mitochondrial membrane potential of cancer cells than normal cells, the AIE‐mito‐TPP probe can selectively accumulate in cancer‐cell mitochondria and light up its fluorescence. More importantly, the probe exhibits selective cytotoxicity for studied cancer cells over normal cells. The high potency of AIE‐mito‐TPP correlates with its strong ability to aggregate in mitochondria, which can efficiently decrease the mitochondria membrane potential and increase the level of intracellular reactive oxygen species (ROS) in cancer cells. The mitochondrial light‐up probe provides a unique strategy for potential image‐guided therapy of cancer cells.     

Fluorescent PEGulated Oligourethane Nanoparticles for Long‐Term Cellular Tracing

We have introduced a new ABA‐type amphiphilic block copolymer consisting of functional oligourethane hydrophobic blocks and two polyethylene glycol (PEG) hydrophilic blocks. The polymer was synthesized in a single step by step‐growth polymerization between two monomers, namely tetraphenylethylene (TPE)‐diol and hexamehylene di‐isocyanate in the presence of a monofunctional impurity PEG‐2000. The polymer exhibits facile self‐assembly in water by synergistic effects of H‐bonding and π–π interaction among the oligourethane core, leading to the formation of robust nanoparticles with remarkable aggregation‐induced emission (AIE). These nanoparticles show very low critical aggregation concentration, stability over a large pH window, and excellent biocompatibility as revealed by an MTT assay. Cellular imaging with cancer cells showed facile cellular uptake and, more importantly, retention of AIE in cellular milieu for long times, which was successfully utilized for long‐term cancer cell tracking.     

Far‐Red/Near‐Infrared Emissive (1,3‐Dimethyl)barbituric Acid‐Based AIEgens for High‐Contrast Detection of Metastatic Tumors in the Lung

Despite of the enthusiastic research in aggregation‐induced emission luminogens (AIEgens) in recent years, the ones that can be smoothly used for sophisticated biomedical applications such as in vivo bioimaging of pulmonary metastatic tumors during surgery are still limited. Herein, we report the design and synthesis of a new series of far‐red/near‐infrared (FR/NIR) fluorescent AIEgens that consist of methoxy‐substituted tetraphenylethene (TPE) as the electron‐donating moiety, (1,3‐dimethyl)barbituric acid as the electron‐withdrawing moiety, and different π‐bridge units. As compared to benzene or 3,4‐ethylenedioxythiophene, using thiophene as the π‐conjugation unit between the donor and acceptor results in a relatively higher absolute fluorescence quantum yield (14.5 %) in water when formulating the corresponding AIEgens into nanoparticles (AIE dots) with an amphiphilic co‐polymer as the doping matrix. The highly FR/NIR‐emissive thiophene‐based AIE dots are demonstrated to be potent for intraoperative detection of pulmonary metastatic tumors, particularly the micro‐sized ones, with excellent signal‐to‐background ratio.     

Aggregation‐Induced Emission and Aggregation‐Promoted Photo‐oxidation in Thiophene‐Substituted Tetraphenylethylene Derivative

Aggregation‐induced emission combined with aggregation‐promoted photo‐oxidation has been reported only in two works quite recently. In fact, this phenomenon is not commonly observed for AIE‐active molecules. In this work, a new tetraphenylethylene derivative (TPE‐4T) with aggregation‐induced emission (AIE) and aggregation‐promoted photo‐oxidation was synthesized and investigated. The pristine TPE‐4T film exhibits strong bluish‐green emission, which turns to quite weak yellow emission after UV irradiation. Interestingly, after solvent treatment, the weakly fluorescent intermediate will become bright‐yellow emitting. Moreover, the morphology of the TPE‐4T film could be regulated by UV irradiation. The wettability of the TPE‐4T microcrystalline surface is drastically changed from hydrophobic to hydrophilic. This work contributes a new member to the aggregation induced photo‐oxidation family and enriches the photo‐oxidation study of tetraphenylethylene derivatives.     

An AIEgen‐Peptide Conjugate as a Phototheranostic Agent for Phagosome‐Entrapped Bacteria

The detection and elimination of intracellular bacteria remain a major challenge. In this work, we report an aggregation‐induced emission (AIE) bioprobe that can detect bacterial infection and kill bacteria surviving inside macrophages through a dynamic process, notably specific molecular tailoring of the probe by caspase‐1 activation in infected macrophages and accumulation of the residue on phagosomes containing bacteria, leading to light‐up fluorescent signals. Moreover, the AIEgen can serve as a photosensitizer for generation of reactive oxygen species (ROS); and the average ROS indicator fluorescent signal intensity per unit area in the bacterial phagosomes is approximately 2.7‐fold higher than that in the cytoplasm. This, in turn, induces bacteria killing with high efficiency and minimal cytotoxicity towards macrophages. We envision that this specific light‐up bioprobe may provide a new approach for selective and sensitive detection and eradication of intracellular bacterial infections.     

Self‐Assembly of Aggregation‐Induced‐Emission Molecules

The last decade has witnessed rapid developments in aggregation‐induced emission (AIE). In contrast to traditional aggregation, which causes luminescence quenching (ACQ), AIE is a reverse phenomenon that allows robust luminescence to be retained in aggregated and solid states. This makes it possible to fabricate various highly efficient luminescent materials, which opens new paradigms in a number of fields, such as imaging, sensing, medical therapy, light harvesting, light‐emitting devices, and organic electronic devices. Of the various important features of AIE molecules, their self‐assembly behavior is very attractive because the formation of a well‐defined emissive nanostructure may lead to advanced applications in diverse fields. However, due to the nonplanar topology of AIEgens, it is not easy for them to self‐assemble into well‐defined structures. To date, some strategies have been proposed to achieve the self‐assembly of AIEgens. Herein, we summarize the most recent approaches for the self‐assembly of AIE molecules. These approaches can be sorted into two classes: 1) covalent molecular design and 2) noncovalent supramolecular interactions. We hope this will inspire more excellent work in the field of AIE.     

High‐Performance Quinoline‐Malononitrile Core as a Building Block for the Diversity‐Oriented Synthesis of AIEgens

In vivo fluorescent monitoring of physiological processes with high‐fidelity is essential in disease diagnosis and biological research, but faces extreme challenges due to aggregation‐caused quenching (ACQ) and short‐wavelength fluorescence. The development of high‐performance and long‐wavelength aggregation‐induced emission (AIE) fluorophores is in high demand for precise optical bioimaging. The chromophore quinoline‐malononitrile (QM) has recently emerged as a new class of AIE building block that possesses several notable features, such as red to near‐infrared (NIR) emission, high brightness, marked photostability, and good biocompatibility. In this minireview, we summarize some recent advances of our established AIE building block of QM, focusing on the AIE mechanism, regulation of emission wavelength and morphology, the facile scale‐up and fast preparation for AIE nanoparticles, as well as potential biomedical imaging applications.     

Visualization of Atom Transfer Radical Polymerization by Aggregation‐Induced Emission Technology

Aggregation‐induced emission (AIE) technology has been demonstrated to be a facile approach for in‐situ monitoring atom transfer radical polymerization (ATRP). A series of tertraphenyl ethylene (TPE)‐containing α‐bromo compounds were synthesized and applied as ATRP initiators. The photoluminescent (PL) emission of the polymerization system is proved to be sensitive to the local viscosity owing to the AIE characteristics of TPE. Linear relationships between the resulting molecular weight M_n and PL intensity were observed in several polymerization systems with different monomers, indicating the variability of this technique. Compared to physical blending, the chemical bonding of the TPE group in the chain end has higher sensitivity and accuracy to the polymer segments and the surrounding environment. This work promoted the combination of the AIE technique and controlled living radical polymerization, and introduced such an optical research platform to the ATRP polymerization process.     

In Situ Probing Intracellular Drug Release from Redox‐Responsive Micelles by United FRET and AIE

Redox‐responsive micelles are versatile nanoplatforms for on‐demand drug delivery, but the in situ evaluation of drug release is challenging. Fluorescence resonance energy transfer (FRET) technique shows potential for addressing this, while the aggregation‐caused quenching effect limits the assay sensitivity. The aim of the current work is to combine aggregation‐induced emission (AIE) probe with FRET to realize drug release assessment from micelles. Tetraphenylethene (TPE) is selected as AIE dye and curcumin (Cur) is chosen as the model drug as well as FRET receptor. The drug is covalently linked to a block copolymer via the disulfide bond linker and TPE is also chemically linked to the polymer via an amide bond; the obtained amphiphilic polymer conjugate self‐assembles into micelles with a hydrodynamic size of ≈125 nm. Upon the supplement of glutathione or tris(2‐carboxyethyl)phosphine) trigger (10 × 10⁻³m ), the drug release induces the fluorescence increase of both TPE and Cur. Accompanied with the FRET decay, absorption enhancement and particle size increase are observed. The same phenomenon is observed in MCF‐7 cells. The FRET–AIE approach can be a useful addition to the spectrum of available methods for monitoring drug release from stimuli‐responsive nanomedicine.     

Novel Functional Conjugative Hyperbranched Polymers with Aggregation‐Induced Emission: Synthesis Through One‐Pot “A2+B4” Polymerization and Application as Explosive Chemsensors and PLEDs

With the aim to develop new tetraphenylethylene (TPE)‐based conjugated hyperbranched polymer, TPE units, one famous aggregation‐induced emission (AIE) active group, are utilized to construct hyperbranched polymers with three other aromatic blocks, through an “A₂+B₄” approach by using one‐pot Suzuki polycondensation reaction. These three hyperbranched polymers exhibit interesting AIEE behavior and act as explosive chemsensors with high sensitivity both in the nanoparticles and solid states. This is the first report of the AIE activity of the TPE‐based conjugated hyperbranched polymers. Their corresponding PLED devices also demonstrate good performance.     

An AIE-Active Conjugated Polymer with High ROS-Generation Ability and Biocompatibility for Efficient Photodynamic Therapy of Bacterial Infections

New, biocompatible materials with favorable antibacterial activity are highly desirable. In this work, we develop a unique conjugated polymer featuring aggregation-induced emission (AIE) for reliable bacterial eradication. Thanks to the AIE and donor-π-acceptor structure, this polymer shows a high reactive oxygen species (ROS)-generation ability compared to a low-mass model compound and the common photosensitizer Chlorin E6. Moreover, the selective binding of pathogenic microorganisms over mammalian cells was found, demonstrating its biocompatibility. The effective growth inhibition of bacteria upon polymer treatment under light irradiation was validated in vitro and in vivo. Notably, the recovery from infection after treatment with our polymer is faster than that with cefalotin. Thus, this polymer holds great promise in fighting against bacteria-related infections in practical applications.     

1,1‐Diphenylvinylsulfide as a Functional AIEgen Derived from the Aggregation‐Caused‐Quenching Molecule 1,1‐Diphenylethene through Simple Thioetherification

An efficient and readily scalable thioetherification between 1,1‐diphenylethene (DPE) and sodium arylsulfinate was developed for the synthesis of 1,1‐diphenylvinylsulfide (DPVS) with the yield up to 99 %. The photophysical properties of DPVS show that the introduction of arylsulfenyl groups onto the parent molecule DPE makes DPVS a novel type of aggregation‐induced emission (AIE) luminogen (AIEgen) with large Stoke's shift (up to 188 nm). These DPVS possess AIE properties due to restriction of intramolecular motions (RIM), as demonstrated by crystal structure analysis. Importantly, the AIE performance of DPVS can be applied to sense the nitroaromatic explosive picric acid in aqueous systems through a “turn‐off” response.     

Imaging Macrophage Phagocytosis Using AIE Luminogen‐Labeled E. coli

Phagocytosis of bacteria is an important biological process. Gaining insight into this process may greatly benefit related pathological studies and further contribute to development of therapies for infectious diseases. Tools for studying these internalization processes, however, are limited. Herein, we demonstrate the feasibility of employing an environmentally sensitive aggregation‐induced emission (AIE) probe for bacteria labeling and imaging. By tracking the fluorescence variation of the stained bacteria, the pH changes of its microenvironment can be monitored. In this way, the phagocytic entry of these bacteria into the macrophage cells and the intravacuolar acidification can be visualized in real‐time.     

Planar AIEgens with Enhanced Solid‐State Luminescence and ROS Generation for Multidrug‐Resistant Bacteria Treatment

Planar luminogens have encountered difficulties in overcoming intrinsic aggregation‐caused emission quenching by intermolecular π‐π stacking interactions. Although excited‐state double‐bond reorganization (ESDBR) can guide us on designing planar aggregation‐induced emission (AIE) luminogens (AIEgens), its mechanism has yet been elucidated. Major challenges in the field include methods to efficiently restrict ESDBR and enhance AIE performance without using bulky substituents (e.g., tetraphenylethylene and triphenylamine). In this study, we rationally developed fluoro‐substituent AIEgens with stronger intermolecular H‐bonding interaction for restricted molecular motions and increased crystal density, leading to decreased nonradiative decay rate by one order of magnitude. The adjusted ESDBR properties also show a corresponding response to variation in viscosity. Furthermore, their aggregation‐induced reactive oxygen species (ROS) generations have been discovered. The application of such planar AIEgen in treating multidrug‐resistant bacteria has been demonstrated in a mouse model. The relationship between ROS generation and distinct E/Z‐configurational stacking behaviors have been further understood, providing a design principle for synthesizing planar AIEgen‐based photosensitizers.     

Mapping Live Cell Viscosity with an Aggregation‐Induced Emission Fluorogen by Means of Two‐Photon Fluorescence Lifetime Imaging

Intracellular viscosity is a crucial parameter that indicates the functioning of cells. In this work, we demonstrate the utility of TPE‐Cy, a cell‐permeable dye with aggregation‐induced emission (AIE) property, in mapping the viscosity inside live cells. Owing to the AIE characteristics, both the fluorescence intensity and lifetime of this dye are increased along with an increase in viscosity. Fluorescence lifetime imaging of live cells stained with TPE‐Cy reveals that the lifetime in lipid droplets is much shorter than that from the general cytoplasmic region. The loose packing of the lipids in a lipid droplet results in low viscosity and thus shorter lifetime of TPE‐Cy in this region. It demonstrates that the AIE dye could provide good resolution in intracellular viscosity sensing. This is also the first work in which AIE molecules are applied in fluorescence lifetime imaging and intracellular viscosity sensing.     

Systemic Studies of Tetraphenylethene–Triphenylamine Oligomers and a Polymer: Achieving Both Efficient Solid‐State Emissions and Hole‐Transporting Capability

By employing a new synthetic strategy, a series of oligomers and a polymer composed of different number of tetraphenylethene and triphenylamine units was designed and synthesised. The optical physics properties and electroluminescence behaviours were studied comparatively. All the molecules demonstrate an aggregation‐induced emission (AIE) phenomenon and bear very high quantum yields in the solid state. The emission wavelengths and quantum efficiencies alternate with the change of the molecular configurations and achieve their maximum at the largest oligomer. The thermal stabilities also become higher along with the increase in the molecular weight. The molecules have suitable HOMO levels that match the work function of the indium tin oxide (ITO) anode. They can act as both light‐emitting and hole‐transporting materials in OLEDs. Thus the present strategy combines the intrinsic emissive nature of AIE materials and the good hole‐transport capability of aromatic amines, thereby achieving a win–win for both optical and electrical properties.     

Franck–Condon Blockade and Aggregation‐Modulated Conductance in Molecular Devices Using Aggregation‐Induced Emission‐Active Molecules

We report an effective modulation of the quantum transport in molecular junctions consisting of aggregation‐induced‐emission(AIE)‐active molecules. Theoretical simulations based on combined density functional theory and rate‐equation method calculations show that the low‐bias conductance of the junction with a single tetraphenylethylene (TPE) molecule can be completely suppressed by strong electron–vibration couplings, that is, the Franck‐Condon blockade effect. It is mainly associated with the low‐energy vibration modes, which is also the origin of the fluorescence quenching of the AIE molecule in solution. We further found that the conductance of the junction can be lifted by restraining the internal motion of the TPE molecule by either methyl substitution on the phenyl group or by aggregation, a mechanism similar to the AIE process. The present work demonstrates the correlation between optical processes of molecules and quantum transport in their junction, and thus opens up a new avenue for the application of AIE‐type molecules in molecular electronics and functional devices.     

Silver Doping‐Induced Luminescence Enhancement and Red‐Shift of Gold Nanoclusters with Aggregation‐Induced Emission

A deep understanding on the luminescence property of aggregation‐induced emission (AIE) featured metal nanoclusters (NCs) is highly desired. This paper reports a systematic study on enhancing the luminescence of AIE‐featured Au NCs, which is achieved by Ag doping to engineer the size/structure and aggregation states of the Au^I‐thiolate motifs in the NC shell. Moreover, by prolonging the reaction time, the luminescence of the as‐synthesized AuAg NCs could be further tailored from orange to red, which is also due to the variation of the Au^I‐thiolate motifs of NCs. This study can facilitate a better understanding of this AIE‐featured luminescent probe and the design of other synthetic routes for this rising family of functional materials.     

Fluorogenic Thorium Sensors Based on 2,6‐Pyridinedicarboxylic Acid‐Substituted Tetraphenylethenes with Aggregation‐Induced Emission Characteristics

A novel fluorescent sensor based on tetraphenylethene (TPE) modified with 2,6‐pyridinedicarboxylic acid (PDA) that shows aggregation‐induced emission (AIE) characteristics for thorium recognition with remarkable fluoresence enhancement response has been synthesized. This sensor is capable of visually distinguishing Th⁴⁺ among lanthanides, transition metals, and alkali metals under UV light. Th⁴⁺ can be detected by the naked eye at ppb levels owing to the AIE phenomenon. The sensor showed high selectivity for Th⁴⁺ compared to all other metals tested, and this recognition displayed good anti‐interference qualities. This study represents the first application of a AIE fluorescence sensor in actinide metal recognition and it has potential applications in environmental systems for thorium ion detection.