Aggregation-induced Emission Luminogens Research Articles

AIE photosensitizers in the first NIR window for high-fidelity imaging of cell membranes and photodynamic anticancer therapy

Irreversible damage to the cell membrane is extremely detrimental to the cell. The synthesis of near-infrared (NIR) aggregation-induced emission luminogens (AIEgens) for high-fidelity imaging of cell membranes and the induction of cancer cell necrosis through photo-driving is a desirable option for tumor treatment, but it remains challenging. In this study, a fluorescent probe molecule (ACTP-1) with an amphiphilic structure and AIE properties was designed and prepared. ACTP-1 can effectively bind with 1,2-dioleo-sn-glycerol-3-phosphatecholine or sensitively detect changes in viscosity in a solution and then emit strong red fluorescence in the first NIR window. Due to its specific embedding of the phospholipid bilayer, the rotational motion of the ACTP-1 molecule was suppressed and the luminescence property was activated, resulting in high resolution and excellent photostability for imaging the cell membrane. Furthermore, ACTP-1, which exhibits a high absorption coefficient in the visible region, can rapidly produce reactive oxygen species (ROS) when exposed to white light. Experiments in cell biology have shown that ACTP-1 can effectively disrupt the cytoskeleton through photodynamic therapy (PDT), leading to cell necrosis instead of apoptosis. This highlights its dual functionality as both a reliable imaging agent and a phototherapy agent.

Thiophene π-bridge-based second near-infrared luminogens with aggregation-induced emission for biomedical applications.

In the past 5years, aggregation-induced emission luminogens (AIEgens) with emission in the second near-infrared (NIR-II) optical window have aroused great interest in bioimaging and disease phototheranostics, benefiting from the merits of deep penetration depth, reduced light scatting, high spatial resolution, and minimal photodamage. To construct NIR-II AIEgens, thiophene derivatives are frequently adopted as π-bridge by virtue of their electron-rich feature and good modifiability. Herein, we summarize the recent progress of NIR-II AIEgens by employing thiophene derivatives as π-bridge mainly compassing unsubstituted thiophene, alkyl thiophene, 3,4-ethylenedioxythiophene, and benzo[c]thiophene, with a discussion on their structure-property relationships and biomedical applications. Finally, a brief conclusion and perspective on this fascinating area are offered.

Synergistically Boosting the Circularly Polarized Luminescence of Functionalized Pillar[5]arenes by Polymerization and Aggregation.

Supramolecular polymers based on chiral macrocycles have attracted increasing attention in the field of circularly polarized luminescence (CPL) owing to their unique properties. However, the construction of macrocyclic supramolecular polymers with highly efficient CPL properties in aggregate states still remains challenging. Herein, w e constructed a class of macrocycle-based coordination polymers by combining the planar chiral properties of pillar[5]arene with the excellent fluorescence properties of aggregation-induced emission luminogens. The formation of polymers enhances both the fluorescence and chiral properties, resulting in chiral supramolecular polymers with remarkable CPL properties. Increasing the aggregation degree of the polymers can further improve their CPL properties, as evidenced by a 21-fold increase in the dissymmetry factor and an over 25-fold increase in the fluorescence quantum yield in the aggregate state compared to the solution state. Such a synergistic effect of polymerization- and aggregation-enhanced CPL can be explained by the restriction of intramolecular motions and aggregation-induced conformation confinement. This work provides a promising method for developing highly efficient CPL supramolecular polymers.

Highly specific characterization and discrimination of monosodium urate crystals in gouty arthritis based on aggregation-induced emission luminogens

Highly specific characterization and discrimination of monosodium urate crystals in gouty arthritis based on aggregation-induced emission luminogens

Improved aggregation-induced emission behavior in D-π-A architectures by modifying the donor units

With the development of aggregation-induced emission (AIE) in optoelectronic devices, stimulus-responsive sensors, optical storage and bioimaging, the design and synthesis of efficient AIE luminogens remains a challenge. Herein, a series of asymmetric pyrene derivatives were prepared by stepwise functionalization at the 1-, 3-positions using traditional reactions. The experimental results show that a promising white-light emitting material (Commission Internationale de L'Eclairage (CIE): x = 0.32, y = 0.31), namely TPxzPy, which has completely separated the highest occupied molecular orbital (HOMOs) and lowest unoccupied molecular orbital (LUMOs) distribution, was produced. Moreover, a new strategy was established to construct pyrene-based AIE luminogens along the short axis. All compounds exhibited higher emission efficiency in the solid or aggregated state versus in solution, especially for TTPaPy with a competitive photoluminescence quantum yield as high as 76.2 %. The present work provides a feasible strategy to construct pyrene-based AIE materials for optoelectronic devices.

A Multifunctional Aggregation-Induced Emission Luminogen with pH-Response Detachable Connector for Lipid Droplet-Specific Imaging and Tracing.

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.

Spinner-Shaped Aggregation-Induced Emission Luminogens for Efficient Blue OLEDs

Spinner-Shaped Aggregation-Induced Emission Luminogens for Efficient Blue OLEDs

More Is Better: Dual-Acceptor Engineering for Constructing Second Near-Infrared Aggregation-Induced Emission Luminogens to Boost Multimodal Phototheranostics.

The manipulation of electron donor/acceptor (D/A) shows an endless impetus for innovating optical materials. Currently, there is booming development in electron donor design, while research on electron acceptor engineering has received limited attention. Inspired by the philosophical idea of "more is different", two systems with D'-D-A-D-D' (1A system) and D'-D-A-A-D-D' (2A system) structures based on acceptor engineering were designed and studied. It was demonstrated that the 1A system presented a weak aggregation-induced emission (AIE) to aggregation-caused quenching (ACQ) phenomenon, along with the increased acceptor electrophilicity and planarity. In sharp contrast, the 2A system with one more acceptor exhibited an opposite ACQ-to-AIE transformation. Interestingly, the fluorophore with a more electron-deficient A-A moiety in the 2A system displayed superior AIE activity. More importantly, all compounds in the 2A system showed significantly higher molar absorptivity (ε) in comparison to their counterparts in the 1A system. Thanks to the highest ε, near-infrared-II (NIR-II, 1000-1700 nm) emission, desirable AIE property, favorable reactive oxygen species (ROS) generation, and high photothermal conversion efficiency, a representative member of the 2A system handily performed in fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal collaborative therapy for efficient tumor elimination. Meanwhile, the NIR-II fluorescence imaging of blood vessels and lymph nodes in living mice was also accomplished. This study provides the first evidence that the dual-connected acceptor tactic could be a new molecular design direction for the AIE effect, resulting in high ε, aggregation-intensified NIR-II fluorescence emission, and improved ROS and heat generation capacities of phototheranostic agents.

Hydrogen-Bonded Polymer Nanomedicine with AIE Characteristic for Intelligent Cancer Therapy.

One of the major goals of biomedical science is to pioneer advanced strategies toward precise and smart medicine. Hydrogen-bonding (H-bonding) assembly incorporated with an aggregation-induced emission (AIE) capability can serve as a powerful tool for developing supramolecular nanomedicine with clear tumor imaging and smart therapeutic performance. We here report a H-bonded polymeric nanoformulation with an AIE characteristic toward smart antitumor therapy. To do so, we first design a structurally novel tetraphenylethylene (TPE)-based H-bonding theranostic prodrug, TPE-(FUA)4, characterized by four chemotherapeutic fluorouracil-1-acetic acid (FUA) moieties arched to the TPE core. A six-arm star-shaped amphiphilic polymer vehicle, P(DAP-co-OEGEA)6, is prepared, bearing hydrophilic and biocompatible POEGEA (poly(oligo (ethylene glycol) ethyl acrylate) segments, along with a hydrophobic and H-bonding PDAP (poly(diaminopyridine acrylamide)) segment. Thanks to the establishment of the DAP/FUA H-bonding association, incorporating the TPE-(FUA)4 prodrug to the P(DAP-co-OEGEA)6 vehicle can yield H-bond cross-linked nanoparticles with interpenetrating networks. For the first time, AIE luminogens are interwoven into a six-arm star-shaped polymer via an intrinsic H-bonding array of the chemotherapeutic agent FUA, thus imposing an effective restriction of TPE molecular rotations. Concomitantly, encapsulated photothermal agent (IR780) via a hydrophobic interaction facilitates the formation of nanoassemblies, TPE-(FUA)4/IR780@P(DAP-co-OEGEA)6, featuring synergistic cancer chemo/photothermal therapy (CT/PTT). Our study can contribute a practical solution to fulfill biomedical requirements with a conductive advance in precision nanomedicine.

Towards bioresource-based aggregation-induced emission luminogens from lignin β-O-4 motifs as renewable resources

One-pot synthesis of heterocyclic aromatics with good optical properties from phenolic β-O-4 lignin segments is of high importance to meet high value added biorefinery demands. However, executing this process remains a huge challenge due to the incompatible reaction conditions of the depolymerization of lignin β-O-4 segments containing γ-OH functionalities and bioresource-based aggregation-induced emission luminogens (BioAIEgens) formation with the desired properties. In this work, benzannulation reactions starting from lignin β-O-4 moieties with 3-alkenylated indoles catalyzed by vanadium-based complexes have been successfully developed, affording a wide range of functionalized carbazoles with up to 92% yield. Experiments and density functional theory calculations suggest that the reaction pathway involves the selective cleavage of double C-O bonds/Diels-Alder cycloaddition/dehydrogenative aromatization. Photophysical investigations show that these carbazole products represent a class of BioAIEgens with twisted intramolecular charge transfer. Distinctions of emission behavior were revealed based on unique acceptor-donor-acceptor-type molecular conformations as well as molecular packings. This work features lignin β-O-4 motifs with γ-OH functionalities as renewable substrates, without the need to apply external oxidant/reductant systems. Here, we show a concise and sustainable route to functional carbazoles with AIE properties, building a bridge between lignin and BioAIE materials.

Color-tunable fluorescent silica-based hybrid film of stacked structure based on a single amphiphilic AIEgen

The large-area and color-tunable fluorescent (FL) films have great potential applications in light-emitting devices and color displays. Yet, the challenge of realizing truly color-tunable emissions using a single fluorophore remains. Herein, we present a large-area, transparent and ultra-stable free-standing FL silica-based film (FSFSF) with color-tunable emissions prepared by using an amphiphilic aggregation-induced emission (AIE) luminogen (AIEgen) as both a structure-directing agent and a light-emitting source. The color-tunable FSFSFs have been facilely prepared at the gas–liquid (GL-FSFSF) and solid–liquid interfaces (SL-FSFSF) by simply stacking the AIEgen/SiO2 composite layers with different self-assembled structures using an approach combining self-assembly with sol-gel process. These films exhibited variable excitation-dependent emission colors, emitting bright blue and green fluorescences as well as dark red fluorescence from one single visual field under excitation with UV, blue, and green lights, respectively. The research found that the resulting GL-FSFSF had a sandwich-like structure with an alternate arrangement of cylindrical and spherical AIEgen micelles in the silica matrix, and exhibited unusual excitation-dependent multi-wavelength and morphology-dependent dual-center emission characteristics. It has been reported that the luminescence of many AIE compounds is morphology-dependent. Therefore, we speculate that the two emission centers of the film are related to the two self-assembled morphologies of amphiphilic AIEgen. Its bright blue and green fluorescence is attributed to the same emission intensity of the two luminescent centers. This study has demonstrated that morphology- and excitation-dependent color-tunable emissions based on one AIE fluorophore can be achieved by incorporating AIEgen aggregates with different self-assembled morphologies in the matrix. Such a simple strategy can be extended to construct other multicolor-tunable FL hybrid materials.

Non-Doped Blue AIEgen-Based OLED with EQE Approaching 10.3 .

Aggregation-induced emission (AIE) luminogens (AIEgens) are attractive for the construction of non-doped blue organic light-emitting diodes (OLEDs) owning to their high emission efficiency in the film state. However, the large internal inversion rate (kIC (Tn) ) between high-lying triplet levels (Tn ) and Tn-1 causes a huge loss of triplet excitons, resulting in dissatisfied device performance of these AIEgens-based non-doped OLEDs. Herein, we designed and synthesized a blue luminogen of DPDPB-AC by fusing an AIEgen of TPB-AC and a DMPPP, which feature hot exciton and triplet-triplet annihilation (TTA) up-conversion process, respectively. DPDPB-AC successfully inherits the AIE feature and excellent horizontal dipole orientation of TPB-AC. Furthermore, it owes smaller kIC (Tn) than TPB-AC. When DPDPB-AC was applied in OLED as non-doped emitting layer, an outstanding external quantum efficiency of 10.3 % and an exceptional brightness of 69311 cd m-2 were achieved. The transient electroluminescent measurements and steady-state dynamic analysis confirm that both TTA and hot exciton processes contribute to such excellent device performance. This work provides a new insight into the design of efficient organic fluorophores by managing high-lying triplet excitons.

Emissive Click Cages.

This study reports the synthesis of cofacial organic cage molecules containing aggregation-induced emissive (AIE) luminogens (AIEgens) through four-fold Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reactions. The shorter AIEgen, tetraphenylethylene (TPE), afforded two orientational isomers (TPE-CC-1A and TPE-CC-1B). The longer AIEgen, tetrabiphenylethylene (TBPE), afforded a single isomer (TBPE-CC-2). The click reaction employed is irreversible, yet it yielded remarkable four-fold click products above 40 %. The phenyl rings around the ethylene core generate propeller-shaped chirality owing to their orientation, which influences the chirality of the resulting cages. The shorter cages are a mixture of PP/MM isomers, while the longer ones are a mixture of PM/MP isomers, as evidenced by their x-ray structures. The newly synthesized cage molecules are emissive even in dilute solutions (THF) and exhibit enhanced AIE upon the addition of water. The aggregated cage molecules in aqueous solution exhibit turn-off emission sensing of nitroaromatic explosives, with selectivity to picric acid in the 25-38 nanomolar detection range.

Chromene-based BioAIEgens: 'in-water' synthesis, regiostructure-dependent fluorescence and ER-specific imaging.

Exploration of artificial aggregation-induced emission luminogens (AIEgens) has garnered extensive interest in the past two decades. In particular, AIEgens possessing natural characteristics (BioAIEgens) have received more attention recently due to the advantages of biocompatibility, sustainability and renewability. However, the extremely limited number of BioAIEgens extracted from natural sources have retarded their development. Herein, a new class of BioAIEgens based on the natural scaffold of chromene have been facilely synthesized via green reactions in a water system. These compounds show regiostructure-, polymorphism- and substituent-dependent fluorescence, which clearly illustrates the close relationship between the macroscopic properties and hierarchical structure of aggregates. Due to the superior biocompatibility of the natural scaffold, chromene-based BioAIEgens can specifically target the endoplasmic reticulum (ER) via the introduction of tosyl amide. This work has provided a new chromene scaffold for functional BioAIEgens on the basis of green and sustainable 'in-water' synthesis, applicable regiostructure-dependent fluorescence, and effective ER-specific imaging.

Facile and green fabrication of tumor- and mitochondria-targeted AIEgen-protein nanoparticles for imaging-guided photodynamic cancer therapy.

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 mitochondria‑targeted 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.

Exploration of Water-Soluble Natural AIEgens Boosting Label-Free Turn-on Fluorescent Sensing in a DNA Hydrogel.

Various aggregation-induced emission luminogens (AIEgens) have been developed and applied in different areas in recent years. However, AIEgens generally can aggregate and emit strong fluorescence in aqueous solution even containing DNA and other biomacromolecules because of poor water solubility, restricting their application in biosensing and bioimaging in aqueous solution. Moreover, the great majority of AIEgens commonly suffer from complex organic synthesis, environmental damage, and biological toxicity. In this work, jatrorrhizine (Jat), an isoquinoline alkaloid from Chinese herbs, was found to be a natural water-soluble AIEgen that has not been previously reported. Jat's photometric characteristics and single-crystal structure demonstrated that the restriction of intramolecular motion and twisted intramolecular charge transfer were responsible for its AIE phenomenon. Due to the good water solubility and AIE character of Jat, it did not emit fluorescence in the aqueous solution containing DNA and polymers until the formation of the DNA hydrogel. Therefore, a DNA hydrogel fluorescence biosensor was designed by using the target (miRNA) as a catalyst to trigger the entropy-driven circuit of DNA, realizing the ultrasensitive and label-free detection of miRNA with an ultralow limit of detection (0.049 fM, S/N = 3). This biosensing strategy also has excellent stability and acceptable reliability for real sample assay. The results not only indicated the excellent sensing performance of Jat as AIE probes in aqueous solution but also demonstrated the promising application potential of water-soluble natural AIEgens.

A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy

Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) and a hypoxia-responsive prodrug for multifunctional image-guided combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence and photoacoustic (PA) brightness for the strong light absorption ability, as well as amplified type I and type II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating the high-performance AIEgen with a hypoxia-responsive paclitaxel (PTX) prodrug into nanoparticles, and further camouflaging with macrophage cell membrane, a tumor-targeting theranostic agent is built. The integration of fluorescence and PA imaging helps to delineate tumor site sensitively, providing accurate guidance for tumor treatment. The light-induced PDT effect could consume the local oxygen and lead to severer hypoxia, accelerating the release of PTX drug. As a result, the combination of PDT and PTX chemotherapy induces immunogenic cancer cell death, which could not only elicit strong antitumor immunity to suppress the primary tumor, but also inhibit the growth of distant tumor in 4T1 tumor-bearing female mice. Here, we report a strategy to develop theranostic agents via rational molecular design for boosting antitumor immunotherapy.

Ratiometric red aggregation-induced emission luminogens for hydrazine hydrate detection

Based on a deprotection reaction and intramolecular charge transfer (ICT) mechanism induced by hydrazine hydrate, a fluorescent probe for the rapid recognition of hydrazine hydrate (N2H4·H2O) was designed. A simple one-step condensation reaction was employed to synthesize a series of novel aggregation-induced emission fluorescent probes with good sensitivity and selectivity for N2H4·H2O. The detection limits for N2H4·H2O using 1 to 3 were 1.51, 0.544 and 2.61 μM, respectively, at a probe concentration of 20.0 μM. Furthermore, probes 1–3 were able to detect N2H4·H2O in living cells and it was found that probes 1–3 could interact with N2H4·H2O to provide an effective tool for on-line monitoring. Moreover, probe 1 is capable of the imaging and tracing of N2H4·H2O in zebrafish.

Observing Extracellular Vesicles Originating from Endothelial Cells in Vivo Demonstrates Improved Astrocyte Function Following Ischemic Stroke via Aggregation-Induced Emission Luminogens.

Extracellular vesicles (EVs) obtained from endothelial cells (ECs) have significant therapeutic potential in the clinical management of individuals with ischemic stroke (IS) because they effectively treat ischemic stroke in animal models. However, because molecular probes with both high labeling efficiency and tracer stability are lacking, monitoring the actions of EC-EVs in the brain remains difficult. The specific intracellular targets in the brain that EC-EVs act on to produce their protective effects are still unknown, greatly impeding their use in clinical settings. For this research, we created a probe that possessed aggregation-induced emission (AIE) traits (namely, TTCP), enabling the effective labeling of EC-EVs while preserving their physiological properties. In vitro, TTCP simultaneously had a higher EC-EV labeling efficiency and better tracer stability than the commercial EV tags PKH-67 and DiI. In vivo, TTCP precisely tracked the actions of EC-EVs in a mouse IS model without influencing their protective effects. Furthermore, through the utilization of TTCP, it was determined that astrocytes were the specific cells affected by EC-EVs and that EC-EVs exhibited a safeguarding impact on astrocytes following cerebral ischemia-reperfusion (I/R) injury. These protective effects encompassed the reduction of the inflammatory reaction and apoptosis as well as the enhancement of cell proliferation. Further analysis showed that miRNA-155-5p carried by EC-EVs is responsible for these protective effects via regulation of the c-Fos/AP-1 pathway; this information provided a strategy for IS therapy. In conclusion, TTCP has a high EC-EV labeling efficiency and favorable in vivo tracer stability during IS therapy. Moreover, EC-EVs are absorbed by astrocytes during cerebral I/R injury and promote the restoration of neurological function through the regulation of the c-Fos/AP-1 signaling pathway.

AIEgen-based nanotherapeutic strategy for enhanced FLASH irradiation to prevent tumour recurrence and avoid severe side effects

Compared with conventional radiotherapy, ultrahigh dose-rate (FLASH) radiotherapy spares normal tissues through oxygen exhaustion. However, residual cancer stem cells (CSCs) may generate tumour cells, causing tumour recurrence, which represents a critical problem after radiotherapy. Here we developed platelet cell membrane-camouflaged hollow TaOx nanospheres encapsulated with aggregation-induced emission luminogens (AIEgen) (named TPT). With characteristics derived from platelets, TPT nanoparticles (NPs) specifically target tumour regions and enhance FLASH radiotherapy via promoting the photoelectric effect by high Z-element tantalum and elevating reactive oxygen species levels through AIEgen-mediated photodynamic therapy (PDT). Under FLASH radiotherapy, TPT NPs exhibited a remarkable CSC killing effect, significantly inhibiting tumour recurrence. More important, compared with conventional radiotherapy, TPT NPs-promoted FLASH radiotherapy to efficiently eliminate tumours while reducing reoccurrence and severity of complications affecting normal tissues. This strategy provides a novel design to suppress tumour recurrence as well as to avoid adverse side effects.