Mechanochemical Fabrication of Full-Color Luminescent Materials from Aggregation-Induced Emission Prefluorophores for Information Storage and Encryption.

The development of luminescent materials via mechanochemistry embodies a compelling yet intricate frontier within materials science. Herein, we delineate a methodology for the synthesis of brightly luminescent polymers, achieved by the mechanochemical coupling of aggregation-induced emission (AIE) prefluorophores with generic polymers. An array of AIE moieties tethered to the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical are synthesized as prefluorophores, which initially exhibit weak fluorescence due to intramolecular quenching. Remarkably, the mechanical coupling of these prefluorophores with macromolecular radicals, engendered through ball milling of generic polymers, leads to substantial augmentation of fluorescence within the resultant polymers. We meticulously evaluate the tunable emission of the AIE-modified polymers, encompassing an extensive spectrum from the visible to the near-infrared region. This study elucidates the potential of such materials in stimuli-responsive systems with a focus on information storage and encryption displays. By circumventing the complexity inherent to the conventional synthesis of luminescent polymers, this approach contributes a paradigm to the field of AIE-based polymers with implications for advanced technological applications.

Platinum complexes with aggregation-induced emission.

Transition metal-containing materials with aggregation-induced emission (AIE) have brought new opportunities for the development of biological probes, optoelectronic materials, stimuli-responsive materials, sensors, and detectors. Coordination compounds containing the platinum metal have emerged as a promising option for constructing effective AIE platinum complexes. In this review, we classified AIE platinum complexes based on the number of ligands. We focused on the development and performance of AIE platinum complexes with different numbers of ligands and discussed the impact of platinum ion coordination and ligand structure variation on the optoelectronic properties. Furthermore, this review analyzes and summarizes the influence of molecular geometries, stacking models, and aggregation environments on the optoelectronic performance of these complexes. We provided a comprehensive overview of the AIE mechanisms exhibited by various AIE platinum complexes. Based on the unique properties of AIE platinum complexes with different numbers of ligands, we systematically summarized their applications in electronics, biological fields, etc. Finally, we illustrated the challenges and opportunities for future research on AIE platinum complexes, aiming at giving a comprehensive summary and outlook on the latest developments of functional AIE platinum complexes and also encouraging more researchers to contribute to this promising field.

Unrestricted molecular motions enable mild photothermy for recurrence-resistant FLASH antitumor radiotherapy.

Ultrahigh dose-rate (FLASH) radiotherapy is an emerging technology with excellent therapeutic effects and low biological toxicity. However, tumor recurrence largely impede the effectiveness of FLASH therapy. Overcoming tumor recurrence is crucial for practical FLASH applications. Here, we prepared an agarose-based thermosensitive hydrogel containing a mild photothermal agent (TPE-BBT) and a glutaminase inhibitor (CB-839). Within nanoparticles, TPE-BBT exhibits aggregation-induced emission peaked at 900 nm, while the unrestricted molecular motions endow TPE-BBT with a mild photothermy generation ability. The balanced photothermal effect and photoluminescence are ideal for phototheranostics. Upon 660-nm laser irradiation, the temperature-rising effect softens and hydrolyzes the hydrogel to release TPE-BBT and CB-839 into the tumor site for concurrent mild photothermal therapy and chemotherapy, jointly inhibiting homologous recombination repair of DNA. The enhanced FLASH radiotherapy efficiently kills the tumor tissue without recurrence and obvious systematic toxicity. This work deciphers the unrestricted molecular motions in bright organic fluorophores as a source of photothermy, and provides novel recurrence-resistant radiotherapy without adverse side effects.

Glutathione-responsive Aggregation-induced Emission Photosensitizers for Enhanced Photodynamic Therapy of Lung Cancer.

Lung cancer, a highly prevalent and lethal form of cancer, is often associated with oxidative stress. Photodynamic therapy (PDT) has emerged as a promising alternative therapeutic tool in cancer treatments, but its efficacy is closely correlated to the photosensitizers generating reactive oxygen species (ROS) and the antioxidant capacity of tumor cells. In particular, glutathione (GSH) can reduce the ROS and thus compromise PDT efficacy. In this study, a GSH-responsive near-infrared photosensitizer (TBPPN) based on aggregation-induced emission for real-time monitoring of GSH levels and enhanced PDT for lung cancer treatment is developed. The strategic design of TBPPN, consisting of a donor-acceptor structure and incorporation of dinitrobenzene, enables dual functionality by not only the fluorescence being activated by GSH but also depleting GSH to enhance the cytotoxic effect of PDT. TBPPN demonstrates synergistic PDT efficacy in vitro against A549 lung cancer cells by specifically targeting different cellular compartments and depleting intracellular GSH. In vivo studies further confirm that TBPPN can effectively inhibit tumor growth in a mouse model with lung cancer, highlighting its potential as an integrated agent for the diagnosis and treatment of lung cancer. This approach enhances the effectiveness of PDT for lung cancer and deserves further exploration of its potential for clinical application.

Exciting Bacteria to a Hypersensitive State for Enhanced Aminoglycoside Therapy by a Rationally Constructed AIE Luminogen.

The diminishing effectiveness of existing aminoglycoside antibiotics (AGs) compels scientists to seek new approaches to enhance the sensitivity of current AGs. Despite ongoing efforts, currently available approaches remain restricted. Herein, a novel strategy involving the rational construction of an aggregation-induced-emission luminogen (AIEgen) is introduced to significantly enhance Gram-positive bacteria's susceptibility to AGs. The application of this approach involves the simple addition of AIEgens to bacteria followed by a 5 min light irradiation. Under light exposure, AIEgens efficiently generate reactive oxygen species (ROS), elevating intrabacterial ROS levels to a nonlethal threshold. Post treatment, the bacteria swiftly enter a hypersensitive state, resulting in a 21.9-fold, 15.5-fold, or 7.2-fold increase in susceptibility to three AGs: kanamycin, gentamycin, and neomycin, respectively. Remarkably, this approach is specific to AGs, and the induced hypersensitivity displays unparalleled longevity and heritability. Further in vivo studies confirm a 7.0-fold enhanced bactericidal ability of AGs against Gram-positive bacteria through this novel approach. This research not only broadens the potential applications of AIEgens but also introduces a novel avenue to bolster the effectiveness of AGs in combating bacterial infections.

Recyclable and Environmentally Friendly Magnetic Nanoparticles with Aggregation-Induced Emission Photosensitizer for Sustainable Bacterial Inactivation in Water.

Bacterial photodynamic inactivation based on the combined actions of photosensitizers, light, and oxygen presents a promising alternative for eliminating bacteria compared to conventional water disinfection methods. However, a significant challenge in this approach is the inability to retrieve photosensitizers after phototreatment, posing potential adverse environmental impacts. Additionally, conventional photosensitizers often exhibit limited photostability and photodynamic efficiency. This study addresses these challenges by employing an aggregation-induced emission (AIE) photosensitizer, iron oxide magnetic nanoparticles (Fe3O4 MNPs), and Pluronic F127 to fabricate AIE magnetic nanoparticles (AIE MNPs). AIE MNPs not only exhibit fluorescence imaging capabilities and superior photosensitizing ability but also demonstrate broad-spectrum bactericidal activities against both Gram-positive and Gram-negative bacteria. The controlled release of TPA-Py-PhMe and magnetic characteristics of the AIE MNPs facilitate reuse and recycling for multiple cycles of bacterial inactivation in water. Our findings contribute valuable insights into developing environmentally friendly disinfectants, emphasizing the full potential of AIE photosensitizers in photodynamic inactivation beyond biomedical applications.

Co-aggregation as A Simple Strategy for Preparing Fluorogenic Tetrazine Probes with On-Demand Fluorogen Selection.

Life science has progressed with applications of fluorescent probes-fluorophores linked to functional units responding to biological events. To meet the varied demands across experiments, simple organic reactions to connect fluorophores and functional units have been developed, enabling the on-demand selection of fluorophore-functional unit combinations. However, organic synthesis requires professional equipment and skills, standing as a daunting task for life scientists. In this study, we present a simple, fast, and convenient strategy for probe preparation: co-aggregation of hydrophobic molecules. We focused on tetrazine-a difficult-to-prepare yet useful functional unit that provides effective bioorthogonal reactivity and strong fluorogenicity. Simply mixing the tetrazine molecules and aggregation-induced emission (AIE) luminogens in water, co-aggregation is induced, and the emission of AIE luminogens is quenched. Subsequent click reaction bioorthogonally turns on the emission, identifying these coaggregates as fluorogenic probes. Thanks to this bioorthogonal fluorogenicity, we established a new time-gated fluorescence bioimaging technique to distinguish overlapping emission signals, enabling multi-organelle imaging with two same-color fluorophores. Our study showcases the potential of this co-aggregation method for the on-demand preparation of fluorescent probes as well as protocols and molecular design principles in this approach, offering an effective solution to evolving needs in life science research.

Integrating Anion-π+ Interaction and Crowded Conformation to Develop Multifunctional NIR AIEgen for Effective Tumor Theranostics via Hippo-YAP Pathway.

The technology of aggregation-induced emission (AIE) presents a promising avenue for fluorescence imaging-guided photodynamic cancer therapy. However, existing near-infrared AIE photosensitizers (PSs) frequently encounter limitations, including tedious synthesis, poor tumor retention, and a limited understanding of the underlying molecular biology mechanism. Herein, an effective molecular design paradigm of anion-π+ interaction combined with the inherently crowded conformation that could enhance fluorescence efficacy and reactive oxygen species generation was proposed through a concise synthetic method. Mechanistically, upon photosensitization, the Hippo signaling pathway contributes to the death of melanoma cells and promotes the nuclear location of its downstream factor, yes-associated protein, which regulates the transcription and expression of apoptosis-related genes. The finding in this study would trigger the development of high-performance and versatile AIE PSs for precision cancer therapy based on a definite regulatory mechanism.

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.

Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy.

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response and boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable of triggering both pyroptosis and ferroptosis remains limited. Here we show the construction of a covalent organic framework (COF-919) from planar and twisted AIEgen-based motifs as a dual-inducer of pyroptosis and ferroptosis for efficient antitumor immunity. Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, and longer lifetime to favor the generation of reactive oxygen species (ROS) and photothermal conversion, triggering pyroptosis. Because of its good ROS production capability, it upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. Additionally, the induction of pyroptosis and ferroptosis by COF-919 effectively inhibits tumor metastasis and recurrence, resulting in over 90% tumor growth inhibition and cure rates exceeding 80%.

Powerful Synergy of Traditional Chinese Medicine and Aggregation-Induced Emission-Active Photosensitizer in Photodynamic Therapy.

Breast cancer (BC) remains a significant global health challenge for women despite advancements in early detection and treatment. Isoliquiritigenin (ISL), a compound derived from traditional Chinese medicine, has shown potential as an anti-BC therapy, but its low bioavailability and poor water solubility restrict its effectiveness. In this study, we created theranostic nanoparticles consisting of ISL and a near-infrared (NIR) photosensitizer, TBPI, which displays aggregation-induced emission (AIE), with the goal of providing combined chemo- and photodynamic therapies (PDT) for BC. Initially, we designed an asymmetric organic molecule, TBPI, featuring a rotorlike triphenylamine as the donor and 1-methylpyridinium iodide as the acceptor, which led to the production of reactive oxygen species in mitochondria. We then combined TBPI with ISL and encapsulated them in DSPE-PEG-RGD nanoparticles to produce IT-PEG-RGD nanoparticles, which showed high affinity for BC, better intersystem crossing (ISC) efficiency, and Förster resonance energy transfer (FRET) between TBPI and ISL. In both 4T1 BC cell line and a 4T1 tumor-bearing BC mouse model, the IT-PEG-RGD nanoparticles demonstrated excellent drug delivery, synergistic antitumor effects, enhanced tumor-killing efficacy, and reduced drug dosage and side effects. Furthermore, we exploited the optical properties of TBPI with ISL to reveal the release process and distribution of nanoparticles in cells. This study provides a valuable basis for further exploration of IT-PEG-RGD nanoparticles and their anticancer mechanisms, highlighting the potential of theranostic nanoparticles in BC treatment.

AIEgen-Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy.

The engineering of aggregation-induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA-COF, BTDTA-COF, and BTDBETA-COF are reported, as hyperthermia agents for inhibiting the occurrence of malignant ventricular arrhythmias (VAs). These AIE COFs exhibit dual functionality, as they not only directly modulate the function and neural activity of stellate ganglion (SG) through local hyperthermia therapy (LHT) but also induce the browning of white fat and improve the neuroinflammation peri-SG microenvironment, which is favorable for inhibiting ischemia-induced VAs. In vivo studies have confirmed that BTDBETA-COF-mediated LHT enhances thermogenesis and browning-related gene expression, thereby serving a synergistic role in combating VAs. Transcriptome analysis of peri-SG adipose tissue reveals a substantial downregulation of inflammatory cytokines, highlighting the potency of BTDBETA-COF-mediated LHT in ameliorating the neuroinflammation peri-SG microenvironment and offering myocardial and arrhythmia protection. The work on AIE COF-based hyperthermia agent for VAs inhibition provides a new avenue for mitigating cardiac sympathetic nerve hyperactivity.

The Role of Structural Hydrophobicity on Cationic Amphiphilic Aggregation-Induced Emission Photosensitizer-Bacterial Interaction and Photodynamic Efficiency.

The aggregation-induced emission photosensitizer (AIE PS) has stood out as an alternative and competent candidate in bacterial theranostics, particularly with the use of cationic AIE PS in bacterial discrimination and elimination. Most reported work emphasizes the role of electrostatic interaction between cationic AIE PS and negatively charged bacterial surfaces, enabling broad applications from bacterial discrimination to bacterial killing. However, the underlying targeting mechanism and the design rationale of the cationic AIE PS for effective bacterial labeling remain poorly investigated. In this Article, we designed and synthesized a series of cationic amphiphilic AIE PSs with different calculated log P values. Then, we systemically studied the relationship between the hydrophobicity variation of AIE PS and bacterial targeting outcomes, the dose of AIE PS needed to label various species of bacteria, and their photodynamic antibacterial efficiency. The findings in this work provide a better understanding of the unclear AIE PS-bacterial interaction mechanism and some insights into the structural design strategies of cationic amphiphilic AIE PS for better development in bacterial theranostics.

In Vivo Aggregation of Clearable Bimetallic Nanoparticles with Interlocked Surface Motifs for Cancer Therapeutics Amplification.

Although renal-clearable luminescent metal nanoparticles (NPs) have been widely developed, their application to efficient cancer therapy is still limited due to low reactive oxygen species (ROS) production. Here, a novel system of clearable mercaptosuccinic acid (MSA) coated Au-Ag bimetallic NPs is designed to enhance ROS production. The results show that the strong COO-Ag coordination bonds between the carboxylic acid groups of MSA and Ag atoms on the Au-Ag bimetallic NPs could construct high-rigidity interlocked surface motifs to restrict the intrananoparticle motions for enhanced ROS generation. Moreover, bimetallic NPs exhibit pH-responsive self-assembly capability under the acidic environment inside lysosomes of cancer cells at both in vitro and in vivo, restricting the internanoparticle motions to further boost ROS production. The well-designed bimetallic NPs show high tumor targeting efficiency, fast elimination from the body through rapid liver biotransformation, and extensive destruction to cancer cells, resulting in good security and prominent therapeutic performance.

Activation of Pyroptosis Using AIEgen-Based sp2 Carbon-Linked Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect and apoptosis resistance often limit their therapeutic efficacy. Herein, we demonstrated for the first time that linking luminogens with aggregation-induced emission effect (AIEgens) into COF networks via vinyl linkages was an effective strategy to construct nonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanistic investigations revealed that the formation of the vinyl linkage in the AIE COF endowed it with not only high brightness but also strong light absorption ability, long lifetime, and high quantum yield to favor the generation of reactive oxygen species for eliciting pyroptosis. In addition, the synergized system of the AIE COF and αPD-1 not only effectively eradicated primary and distant tumors but also inhibited tumor recurrence and metastasis in a bilateral 4T1 tumor model.

Aggregation-Induced Emission (AIE), Life and Health.

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

Molecular Engineering of AIE Photosensitizers for Inactivation of Rabies Virus.

Rabies is a zoonotic neurological disease caused by the rabies virus (RABV) that is fatal to humans and animals. While several post-infection treatment have been suggested, developing more efficient and innovative antiviral methods are necessary due to the limitations of current therapeutic approaches. To address this challenge, a strategy combining photodynamic therapy and immunotherapy, using a photosensitizer (TPA-Py-PhMe) with high type I and type II reactive oxygen species (ROS) generation ability is proposed. This approach can inactivate the RABV by killing the virus directly and activating the immune response. At the cellular level, TPA-Py-PhMe can reduce the virus titer under preinfection prophylaxis and postinfection treatment, with its antiviral effect mainly dependent on ROS and pro-inflammatory factors. Intriguingly, when mice are injected with TPA-Py-PhMe and exposed to white light irradiation at three days post-infection, the onset of disease is delayed, and survival rates improved to some extent. Overall, this study shows that photodynamic therapy and immunotherapy open new avenues for future antiviral research.

Restriction of molecular motion to a higher level: Towards bright AIE dots for biomedical applications.

In the late 19th century, scientists began to study the photophysical differences between chromophores in the solution and aggregate states, which breed the recognition of the prototypical processes of aggregation-caused quenching and aggregation-induced emission (AIE). In particular, the conceptual discovery of the AIE phenomenon has spawned the innovation of luminogenic materials with high emission in the aggregate state based on their unique working principle termed the restriction of intramolecular motion. As AIE luminogens have been practically fabricated into AIE dots for bioimaging, further improvement of their brightness is needed although this is technically challenging. In this review, we surveyed the recent advances in strategic molecular engineering of highly emissive AIE dots, including nanoscale crystallization and matrix-assisted rigidification. We hope that this timely summary can deepen the understanding about the root cause of the high emission of AIE dots and provide inspiration to the rational design of functional aggregates.

Adipocyte-Targeting Type I AIE Photosensitizer for Obesity Treatment via Photodynamic Lipid Peroxidation.

Obesity is a surging public health risk and is often associated with fatal diseases, including diabetes, stroke, and myocardial infarction. Common methods for obesity treatment include diet control, weight-loss medicine, and bariatric surgery, but these methods are often ineffective or unsafe. Herein, we introduce a minimally invasive and effective approach to reduce excessive fat accumulation by utilizing red/near-infrared emissive and lipid droplet targeting aggregation-induced emissive luminogens (AIEgens), namely, TTMN and MeTTMN, for specific targeting and photoinduced peroxidation of large lipid droplets in adipocytes. The reported AIEgens can trace and monitor the formation process of adipocytes from pre-adipocytes with a high signal-to-noise ratio. In addition, the presented AIEgens act as Type I photosensitizer that generates highly reactive hydroxyl radicals and superoxides under white light to eliminate mature adipocytes through the chain reactions of lipid peroxidation, even under low oxygen supply. We also demonstrate the use of AIEgens for in vivo photodynamic therapy (PDT) for subcutaneous fat reduction treatment. This work demonstrates the use of AIEgen as a dual imaging and Type I photosensitizer for photodynamic therapeutics to induce adipocyte apoptosis, involving a simple fabrication and treatment process. The suggested in vivo photodynamic obesity treatment processes have negligible toxicity toward nontargeted normal tissues, providing an alternative approach for effective and relatively safer obesity treatment in the future.

Aggregation-Induced Emission Macromolecular Materials for Antibacterial Applications.

Recent advancements in aggregation-induced emission (AIE) macromolecular materials have brought their attention as potential antibacterial solutions, these materials offer new approaches to cure multidrug-resistant infections and biofilms in bacterial infections as well as real-time monitoring and specific targeting of bacteria. This review provides an overview of the three main categories of AIE macromolecular materials with antibacterial properties; namely AIE-active polymers, AIEgen@polymer complexes, and clusterization-triggered emission (CTE) based polymers. The mechanisms and applications of these materials in antibacterial treatment, wound care, and protective equipment are also discussed. The potential for future developments and application directions of AIE-based antimicrobial materials are finally highlighted.