Aggregation-induced Emission Luminogens Research Articles

Double‐pronged Antimicrobial Agents based on a Donor‐π‐Acceptor Type Aggregation‐Induced Emission Luminogen

AbstractNovel antibacterial agents are urgently needed to control the infections induced by multidrug‐resistant (MDR) bacteria. Herein, we rationally designed and facilely synthesized a new D‐π‐A type luminogen with strong red/near‐infrared fluorescence emission, great aggregation‐induced emission (AIE) features, and excellent reactive oxygen species (ROS) production. The newly developed molecule TTTh killed the methicillin‐resistant Staphylococcus aureus (MRSA) by triggering the ROS accumulation in bacteria and interrupting the membrane integrity. Moreover, TTTh specifically targeted the lysosomes and potentiated their maturation to accelerate the clearance of intracellular bacteria. Additionally, reduced bacterial burden and improved healing were observed in TTTh‐treated wounds with negligible side effects. Our study expands the biological design and application of AIE luminogens (AIEgens), and provides new insights into discovering novel antibacterial targets and agents.

Synthesis of D-A typed AIE luminogens in isomeric architecture and their application in latent fingerprints imaging

Among the emitters in powder dusting to visualize the latent fingerprints (LFPs), aggregation-induced emission luminogens (AIEgens) are well employed for their high brightness and resistance to photo-bleaching. However, the serious background interference and low resolution still limit their fast development. Therefore, to further enhance the signal-to-noise ratio in LFPs imaging, especially to improve the analysis for level 3 details, donor-acceptor (D-A) typed AIEgens of DTPA-2,3-P, DTPA-2,5-P and DTPA-2,6-P are designed here. It is observed that strong emission covering from 450 nm to 650 nm can be obtained for all these molecules, especially that a high PLQY value of 10.06% in solids is achieved in DTPA-2,3-P. This is much higher than that of the other two cases (0.80% and 0.51%). By utilizing the DTPA-2,3-P in powder dusting, fluorescence imaging of LFPs can be clearly captured on both smooth and rough substrates. Moreover, confocal laser scanning microscope (CLSM) enables us to achieve high-resolution LFPs imaging in both 2D and 3D views, providing more detailed information of fingerprints pores in width, distance, distribution, and shapes. The results here demonstrate that highly emissive AIEgen of DTPA-2,3-P could be an excellent candidate for the visualization of fingerprints, thus providing the potential application in criminal investigation in the future.

Biodegradable Redox-Responsive AIEgen-Based-Covalent Organic Framework Nanocarriers for Long-Term Treatment of Myocardial Ischemia/Reperfusion Injury.

Timely restoration of blood supply after myocardial ischemia is imperative for the treatment of acute myocardial infarction but causes additional myocardial ischemia/reperfusion (MI/R) injury, which has not been hitherto effectively targeted by interventions for MI/R injury. Hence, the development of advanced nanomedicine that can reduce apoptosis of cardiomyocytes while protecting against MI/R in vivo is of utmost importance. Herein, a redox-responsive and emissive TPE-ss covalent organic framework (COF) nanocarrier by integrating aggregation-induced emission luminogens and redox-responsive disulfide motifs into the COF skeleton is developed. TPE-ss COF allows for efficient loading and delivery of matrine, a renowned anti-cryptosporidial drug, which significantly reduces MI/R-induced functional deterioration and cardiomyocyte injury when injected through the tail vein into MI/R models at 5min after 30min of ischemia. Moreover, TPE-ss COF@Matrine shows a drastic reduction in cardiomyocyte apoptosis and improvements in cardiac function and survival rate. The effect of the TPE-ss COF carrier is further elucidated by enhanced cardiomyocyte viability and triphenyltetrazolium chloride staining in vitro. This work demonstrates the cardioprotective effect of TPE-ss COFs for MI/R injury, which unleashes the immense potential of using COFs as smart drug carriers for the peri-reperfusion treatment of ischemic heart disease with low cost, high stability, and single postoperative intervention.

Platelet membrane camouflaged AIEgen-mediated photodynamic therapy improves the effectiveness of anti-PD-L1 immunotherapy in large-burden tumors.

Although immunotherapy has achieved recent clinical success in antitumor therapy, it is less effective for solid tumors with large burdens. To overcome this challenge, herein, we report a new strategy based on platelet membrane-camouflaged aggregation-induced emission (AIE) luminogen (Plt-M@P) combined with the anti-programmed death ligand 1 (anti-PD-L1) for tumoral photodynamic-immunotherapy. Plt-M@P is prepared by using poly lactic-co-glycolic acid (PLGA)/PF3-PPh3 complex as a nanocore, and then by co-extrusion with platelet membranes. PF3-PPh3 is an AIE-active conjugated polyelectrolyte with photosensitizing capability for photodynamic therapy (PDT). Plt-M@P exhibits superior tumor targeting capacity in vivo. When applied in small tumor-bearing (~40 mm3) mice, Plt-M@P-mediated PDT significantly inhibits tumor growth. In tumor models with large burdens (~200 mm3), using Plt-M@P-mediated PDT or anti-PD-L1 alone is less effective, but the combination of both is effective in inhibiting tumor growth. Importantly, this combination therapy has good biocompatibility, as demonstrated by the absence of damage to the major organs, especially the reproductive system. In conclusion, we show that Plt-M@P-mediated PDT can improve anti-PD-L1 immunotherapy by enhancing antitumor effects, providing a promising strategy for the treatment of tumors with large burdens.

NIR-II AIEgens with Photodynamic Effect for Advanced Theranostics.

Phototheranostics that concurrently integrates accurate diagnosis (e.g., fluorescence and photoacoustic (PA) imaging) and in situ therapy (e.g., photodynamic therapy (PDT) and photothermal therapy (PTT)) into one platform represents an attractive approach for accelerating personalized and precision medicine. The second near-infrared window (NIR-II, 1000–1700 nm) has attracted considerable attention from both the scientific community and clinical doctors for improved penetration depth and excellent spatial resolution. NIR-II agents with a PDT property as well as other functions are recently emerging as a powerful tool for boosting the phototheranostic outcome. In this minireview, we summarize the recent advances of photodynamic NIR-II aggregation-induced emission luminogens (AIEgens) for biomedical applications. The molecular design strategies for tuning the electronic bandgaps and photophysical energy transformation processes are discussed. We also highlight the biomedical applications, such as image-guided therapy of both subcutaneous and orthotopic tumors, and multifunctional theranostics in combination with other treatment methods, including chemotherapy and immunotherapy; and the precise treatment of both tumor and bacterial infection. This review aims to provide guidance for PDT agents with long-wavelength emissions to improve the imaging precision and treatment efficacy. We hope it will provide a comprehensive understanding about the chemical structure–photophysical property–biomedical application relationship of NIR-II luminogens.

Two distinctly fluorescent BioAIEgens originated from the combination of natural rosin and chromophoric triphenylamine

Aggregation-induced emission (AIE) luminogens have been widely used in various fields. Among them, BioAIEgens (AIEgens from natural resources) have been highly concerned by researchers because of their unique advantages. However, the number of BioAIEgens directly derived from nature is limited. Therefore, chemical modification on natural resources may be an effective way to obtain more BioAIEgens. In this paper, because the rigid alicyclic ring of dehydroabietic acid (DA) has the effect of restricting molecular motion, we successfully obtained two rosin-based BioAIEgens (DAA-TPA and DAMBA-TPA) by combining DA with triphenylamine. Interestingly, DAA-TPA obtained by connecting TPA with the aliphatic ring of DA has TICT-AIE and strong solid-state emission properties, while DAMBA-TPA obtained by connecting TPA with the aromatic ring of DA shows an atypical AIE and weak solid emission effect. Two control molecules were designed to investigate the influence of the introduction of aliphatic ring and aromatic ring on the photophysical properties of TPA. The results showed that DA containing both aliphatic ring and aromatic ring may be used as a precursor to construct BioAIEgens with different AIE properties. In addition, based on the fluorescence performance of DAA-TPA, we applied it to the detection of trace water in acetonitrile (ACN).

Aggregation-induced emission luminogens-encoded microspheres preparation and flow-through immunoaffinity chromatographic assay development for microcystin-LR analysis

Despite decades of efforts, we are faced with the daunting task of on-site ultratrace environmental toxins detecting, especially the microcystins caused by water bloom. In this work, a novel fluorescent microsphere-based flow-through immunoaffinity chromatographic assay has been designed for detecting ultratrace microcystin-LR in water and aquatic products. The aggregation-induced emission luminogens were encapsulated into fluorescent microspheres to ensure microcystin-LR quantitation with a whole analytical time of less than 30 min. Furthermore, the colorimetric images were captured and quantitatively analyzed, which offered a limit of detection at 0.217 pg/mL and a limit of quantitation at 0.362 pg/mL in water and aquatic muscle samples. The developed immunoassays provide average recovery ranging from 79.1 % to 95.7 %, with relative standard deviations less than 13.4 %. Thus, the validated flow-through immunoaffinity chromatographic assay is an easy-to-use alternative for on-site screening of microcystin-LR in water and aquatic samples at picogram levels.

An improved ratiometric fluorescent tag based on aggregation-induced emission luminogen for in-situ monitoring of seafood freshness

Volatile basic nitrogens (VBNs) are an important indicator of food freshness. In this work, a novel ratiometric fluorescent sensor was developed. The sensor used blue-green fluorescent N-acetyl-L-cysteine capped silver nanoclusters (NAC-AgNCs) as an indicator and red-orange fluorescent glutathione capped gold nanoclusters (GSH-AuNCs) as an internal reference. With biogenic amines as model targets, results showed that the sensor was sensitive to VBNs with a limit of detection of 3.85 μM and 6.75 μM for spermidine and spermine, respectively. Based on these findings, a ratiometric fluorescent tag was further prepared and applied as a gas sensor for ammonia vapour monitoring, which was employed and validated to monitor the freshness of raw shrimp at different storage temperatures (4 and 25 °C). For all we know, this is the first ratiometric fluorescent tag based on metal nanoclusters with aggregation-induced emission properties for monitoring seafood freshness.

Significantly different fluorescent responses of two aggregation-induced emission probes to heparin

Heparin (Hep) is a widely used clinical anticoagulant which requires regular detection to avoid hemorrhage complication. Herein, we found that Hep could be quantitatively determined by both the four-armed (TPE-4Py) and three-armed (TPA-3Py) cationic water-soluble, aggregation-induced emission (AIE) luminogens. TPE-4Py and TPA-3Py could quantify 5.95 ng/mL to 1.996 mg/L, and 49.53 ng/mL to 6.14 mg/L Hep, with the quantum yield of 25.94% and 7.81%, respectively. In addition, the two probes showed many different fluorescent responses to Hep such as opposite fluorescence spectral shift with increased Hep, and opposite circular dichroism spectra, etc. Finally, the fluorescence emitted by the TPE-4Py binding to sulfate-removed Hep is stronger than that emitted by the TPE-4Py binding to Hep. According to the simulation results, it was probably because that in Hep the third sulfonic group competes with the other two sulfonic groups, thus weakening its binding ability with the two methylated vinylpyridine groups in TPE-4Py. Those demonstrate that small structural changes of the dyes can impact on the binding preference of Hep. On the other hand, the sulfonic group in Hep can take the unexpected way to affect on its binding ability with TEP-4Py. This study helps us to understand the binding preference of Hep with AIE probes and adds important knowledge on Hep interaction with different cationic molecules which could be practically useful for drug development in which Hep is involved.

Hybridization of triphenylamine to BODIPY dyes at the 3,5,8-positions: A facile strategy to construct near infra-red aggregation-induced emission luminogens with intramolecular charge transfer for cellular imaging

A series of five BODIPY derivatives with triarylamine (TPA) moieties on their 3-, 5-, or 8-positions were reported, which showed wide-range fluorescence emissions across red and near infrared regions in their aggregation states. The influences of numbers and substituted positions of TPA groups on the optical and aggregation-induced emission (AIE) properties of these BODIPYs as well as organelle-specific imaging in live cells were investigated. The TPA groups installed at 3-/5-positions of BODIPY could effectively enlarge the conjugated system and red-shift the absorption and emission bands (λemmax up to 815 nm). In contrast, the TPA group linked to 8-position of BODIPY core has little contribution to decrease the HOMO-LUMO energy gap. Importantly, regardless the substitution positions of TPA groups, all these TPA-substituted BODIPYs (BTs) showed remarkable AIE performance and possessed high molar extinction absorption (up to ∼ 63000 M−1 cm−1), two-photon absorption (up to 171 GM at 870 nm), and large Stokes shifts. The BODIPY with one TPA group (BT1 and FBT1) showed lipid droplets-specific localization while BODIPY with two and three TPA groups (BT2, BT3 and FBT2) preferred to enrich in lysosomes. These BODIPYs all have been successfully used in tracking the dynamic behaviors of lipid droplets or lysosomes in living cells. Furthermore, BT1 and FBT1 can quantitatively detect the overexpression of lipid droplets, and BT3 has been successfully used to observe lysosomes behaviors of lipophagy process in living cells. This work systematically studied the influence of the number and position of TPA units on the optical properties and AIE-activities of BODIPYs, which not only enriched the BODIPY-based AIE NIR probes for organelle-specific imaging in live cells, but also provided a practical strategy for the effective construction of organic dyes with NIR AIE activity.

Biological Synthesis and Process Monitoring of an Aggregation-Induced Emission Luminogen-Based Fluorescent Polymer.

As the most abundant and renewable biopolymer on earth, cellulose can be functionalized for various advanced applications by chemical modification. In addition, fluorescent polymers with aggregation-induced emission (AIE) are generally prepared using chemical approaches, and the biosynthesis of AIE-active polymers are rarely investigated. Herein, fluorescent cellulose was successfully synthesized by bacterial fermentation, where glucosamine-modified AIE luminogen was incorporated into cellulose to achieve AIE-active biopolymers. Excitingly, real-time visualization of the synthetic process was realized, which is crucial for investigating the process of bacterial fermentation. The biosynthesized cellulose exhibited better performance with uniform fluorescence distribution and high stability, compared with that prepared by physical absorption. Additionally, fluorescent mats were fabricated by electrospinning of AIE-active cellulose, demonstrating its great potential applications in flexible display and tissue engineering.

Diagnostics and theranostics of central nervous system diseases based on aggregation-induced emission luminogens

Central nervous system (CNS) diseases include Alzheimer's disease (AD), Parkinson's disease (PD), brain tumors, strokes, and other important diseases that are harmful and fatal to human beings. CNS diseases have the characteristics of high fatality rates, difficult diagnosis, and costly treatment. The diagnosis and treatment of CNS diseases by molecular imaging are usually limited by the depth of tissue penetration and the blood-brain barrier (BBB). Therefore, it is still a huge challenge to distinguish between the lesion and the surrounding parenchymal boundary with high sensitivity and specificity. Compared with traditional fluorophores with aggregation-caused quenching effect, luminogens with aggregation-induced emission (AIE) characteristics have strong near-infrared deep penetration, large Stokes shift, excellent biocompatibility, light stability, and desirable BBB permeability. In view of this, developing novel AIE-based materials for diagnostics and theranostics of CNS diseases is promising and of great significance. Herein, we highlight the recent research progress in this field with a special focus on near-infrared imaging and AIE nanorobots for CNS diseases. The design principle of AIE probes is discussed in detail, and the outlook is presented as well.

AIEgens Based on Anion-π+ Interactions: Design, Synthesis, Photophysical Properties, and Their Applications in Material Science and Biology.

The design of novel aggregation-induced emission luminogens (AIEgens), has generally been facilitated by disrupting the possibility of π-π stacking. The recent literature describes a novel strategy to design AIEgens by introducing anion-π+ interactions to prevent the detrimental π-π stacking. This new strategy provides access to intrinsically charged AIEgens whose photophysical properties can be tuned either by incorporating different substituents on the π-molecular scaffold to modulate the acidity for tuning the interaction energy between a π-acceptor and counter-anions. This concept article provides a brief overview of the field, focusing on the synthesis of AIEgens, their photophysical properties, crystallography studies and their applications in live cell fluorescence imaging.

Fluorescent Imaging and Sorting of High-Lipid-Content Strains of Green Algae by Using an Aggregation-Induced Emission Luminogen.

Microalgae-based biofuels are receiving attention at the environmental, economic, and social levels because they are clean, renewable, and quickly produced. The green algae Chlorella vulgaris has been extensively studied in research laboratories and the biofuel industry as a model organism to increase lipid production to be cost-effective in commercial production. In this work, we utilized a lipid-droplet-specific luminogen with aggregation-induced emission (AIE) characteristics to increase the lipid production of C. vulgaris by fluorescent imaging and sorting of those algal cells with large and rich lipid droplets for subculturing. The AIE-active TPA-A enabled real-time monitoring of the size and number of lipid droplets in C. vulgaris during their growth period so that we can identify the best time for harvesting. Furthermore, the algae cells with high lipid content were identified and collected for subculturing by the technique of fluorescence-activated cell sorting (FACS). The lipid production in the generation of two successive selections was almost doubled compared to the generation with natural selection. This work demonstrated that the technologies of AIE and FACS could be applied together to improve the production of a third-generation biofuel.

Sensing Leakage of Electrolytes from Magnesium Batteries Enabled by Natural AIEgens

The potential for leakage of liquid electrolytes from magnesium (Mg) batteries represents a large hurdle to future application. Despite this, there are no efficient sensing technologies to detect the leakage of liquid electrolytes. Here, we developed a sensor using laccaic acid (L-AIEgen), a naturally occurring aggregation-induced emission luminogen (AIEgens) isolated from the beetle Laccifer lacca. L-AIEgen showed good selectivity and sensitivity for Mg2+, a universal component of electrolytes in Mg batteries. Using L-AIEgen, we then produced a smart film (L-AIE-F) that was able to sense leakage of electrolytes from Mg batteries. L-AIE-F showed a strong “turn-on” AIE-active fluorescence at the leakage point of electrolyte from model Mg batteries. To the best of our knowledge, this is the first time that AIE technology has been used to sense the leakage of electrolytes.

Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-II fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes

Owing to the complementary high spatial resolution and signal-to-noise ratio, the dual-modality imaging technique of photoacoustic imaging (PAI)/the second near-infrared window fluorescence imaging (NIR-II FI) holds great promise for the detection of tumor tissues and sentinel lymph nodes (SLNs). Herein, by developing two aggregation-induced emission luminogens (AIEgens) (C-NTBD and O-NTBD) with benzodithiadiazole as the electron acceptor, PAI/NIR-II FI was applied to the diagnosis and treatment of neuroendocrine neoplasms (NENs) and their SLNs for the first time. Both AIEgens exhibited good PAI properties as well as intense NIR-II fluorescence emission. Among them, C-NTBD nanoparticles (NPs) have better PAI and NIR-II FI performance with maximum absorption at 732 nm and emission peak at 1042 nm. In NENs-bearing nude mice model, after successful preoperative localization of NENs by PAI, NIR-II FI was then used to detect SLNs. Under the NIR-II FI guidance of C-NTBD NPs, an SLN with a diameter of 1 mm located in the chest wall and far away from the primary tumor site was even detected and precisely removed. This dual-modality imaging technology could improve the detection of NENs and the accuracy of intraoperative SLNs dissection, improve patient prognosis, and provide a new strategy for the precise treatment of NENs.

Dipole‐Dipole and Anion‐π+ Interaction Manipulation Synergistically Enhance Intrinsic Antibacterial Activities of AIEgens

Pathogenic bacteria infections, especially multidrug resistant bacteria infections have aroused worldwide attention due to their severe threats to human beings. Thus, the development of highly effective antibacterial reagents is very important. However, the design of antimicrobials is still quite challenging for the lack of a universal design strategy. Here, a synergistic manipulation strategy of dipole-dipole and anion-π+ interaction is proposed for constructing highly efficient antimicrobials with aggregation-induced emission (AIE) feature. Firstly, four anion-π+ -type AIE luminogens were designed and synthesized. Due to the electron-donating and hydrophilic characteristic of methoxy groups, 3MOTPO containing three methoxy groups showed the largest dipole moment (5.06 Debye) and dual anion-π+ interactions in the solid state. Driven by both dipole-dipole and anion-π+ interactions, 3MOTPO showed the strongest bacterial binding ability and the best antibacterial activities (MIC90 =3.76 μM). The work offers a deep insight into the rational design of highly efficient antimicrobials for luminescence-guided antibacterial study.

AIEgens functionalized hollow mesoporous silica nanospheres for selective detection of the antimicrobial furazolidone

Scheme Synthesis route of AIEgen functionalized hollow silica nanospheres. • AIE luminogens tetraphenyl ethylene functionalized hollow silica nanospheres (FHMSN) were successfully synthesized through a simple post-graft method. • FHMSN showed sensitive detection for the antibacterial furazolidone based on photo-induced energy transfer quenching process with a high quenching constant of 2.43 × 10 4 M −1 . • FHMSN can selectively detect the furazolidone not disturbed by other pesticides such as glyphosate, benoxacor, glufosinate ammonium, dipterex, clethodim, mesotrione, phosethyl-Al, demonstrating the potential value of AIEgens-functionalized mesoporous materials in environmental protection. Aggregation-induced emission luminogens (AIEgens) functionalized hollow silica nanospheres were synthesized by post-grafing tetraphenylethylene derivatives on the mesoporous material. The fluorecent nanoprobe, marked as FHMSN showed strong blue emission under 340 nm excitation and was used to selectively detect the antibacterial furazolidone in water system, which was based on the dynamic quenching mechanism. It exhibited quick and sensitive response towards furazolidone with a large quenching constant of 2.43 × 10 4 M −1 , while scarcely showed any detection effect towards other water pollutions such as glyphosate, glufosinate ammonium, dipterex, clethodim, benoxacor, mesotrione or phosethyl-Al. These experiment results demonstrate the potential value of AIEgens-functionalized mesoporous materials in environmental protection.

A Ratiometric Organic Fluorescent Nanogel Thermometer for Highly Sensitive Temperature Sensing.

Sensing temperature in biological systems is of great importance, as it is constructive to understanding various physiological and pathological processes. However, the realization of highly sensitive temperature sensing with organic fluorescent nanothermometers remains challenging. In this study, we report a ratiometric fluorescent nanogel thermometer and study its application in the determination of bactericidal temperature. The nanogel is composed of a polarity-sensitive aggregation-induced emission luminogen with dual emissions, a thermoresponsive polymer with a phase transition function, and an ionic surface with net positive charges. During temperature-induced phase transition, the nanogel exhibits a reversible and sensitive spectral change between a red-emissive state and a blue-emissive state by responding to the hydrophilic-to-hydrophobic change in the local environment. The correlation between the emission intensity ratio of the two states and the external temperature is delicately established, and the maximum relative thermal sensitivities of the optimal nanogel are determined to be 128.42 and 68.39% °C−1 in water and a simulated physiological environment, respectively. The nanogel is further applied to indicate the bactericidal temperature in both visual and ratiometric ways, holding great promise in the rapid prediction of photothermal antibacterial effects and other temperature-related biological events.

Structure-property relationship on aggregation-induced emission properties of simple azine-based AIEgens and its application in metal ions detection

In recent twenty years, aggregation-induced emission (AIE), due to its excellent application prospect, has aroused widespread interests. The development of novel and easy to make AIE luminogens (AIEgens) is an attractive subject. For this purpose, it is very important to study the structure-property relationship of AIEgens. Because azine derivatives are easy to synthesis and some of them have nice AIE properties, herein, a series of azine derivatives (ADs) were employed as models to study the influence of different functional groups, electronic effects and structures on the AIE properties of azine derivatives. The AIE mechanism were studied by single crystal analysis, density functional theory (DFT) calculations and so on. The results indicated that the o-hydroxyl aryl substituted azine compounds could show good AIE properties. Meanwhile, the AIE properties of o-hydroxyl aryl substituted azine compounds were also influenced by the electronic effects of the aryl groups in the azine compounds. The o-hydroxyl groups could form intramolecular hydrogen bond with imine group, which play key role to restrict the intramolecular rotation of the aryl groups and act as base stone for the AIE process of this kind compounds. The HOMO-LUMO energy gaps of o-hydroxyl substituted azine are smaller than other homologous compounds, which is agree with the proposed AIE mechanism. Finally, thanks to the AIE properties, the o-hydroxy-substituted azines could be used as efficient Al3+ and Cu2+ fluorescent chemosensors in different conditions. In addition, test strips based on AD10 has been prepared, which can conveniently detect Cu2+ in industrial wastewater. This research supplied a way for the design of novel easy to make AIEgens through simple azine derivatives.