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Solution casting is a common processing method in industrial production. The phase-structure transitions driven by solvent evaporation directly impact the quality of the final film. However, due to the presence of solvents and other additives in the solution, it is difficult to detect the condensed matter structure during the drying process. This work studies structural transitions and heterogeneity of a poly(vinyl alcohol) (PVA) film during water evaporation using glycerol as a plasticizer. Aggregation-induced emission (AIE) molecules are utilized to indicate the change in PVA chain dynamics during evaporation. The gelation, crystallization, and glass transition can be clearly detected via emission intensity change of the AIE molecules during water evaporation. It is found that the critical concentrations triggering structural transitions increase with the glycerol content, attributed to the release of PVA segmental mobility by the plasticizer. Furthermore, structural uniformity in the thickness direction is realized while the PVA film was loaded with 20% glycerol. It is revealed that glycerol diminishing the heterogeneity is due to the dual effect of hydrophilic glycerol reducing the evaporation rate and enhancing diffusion. Finally, the mechanism of the plasticizer in delaying structural transitions and ameliorating the heterogeneity in PVA films is discussed, which could provide theoretical guidance for preparation of polymer films via solution casting.

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. © 2023 American Chemical Society.

Light-mediated therapies such as photodynamic therapy (PDT) are considered emerging cancer treatment strategies. However, there are still lots of defect with common photosensitizers (PSs), such as short emission wavelength, weak photostability, poor cell permeability, and low PDT efficiency. Therefore, it is very important to develop high-performance PSs. Recently, luminogens with aggregation-induced emission (AIE) characteristics and red/near-infrared (NIR) emissive have been reported as promising PSs for image-guided cancer therapy, due to them being able to prevent autofluorescence in physiological environments, their enhanced fluorescence in the aggregated state, and generation of reactive oxygen species (ROS). Herein, we developed PSs named TBTCPM and MTBTCPM with donor–acceptor (D–A) structures, strong red/NIR, excellent targeting specificities to good cell permeability, and high photostability. Interestingly, both of them can efficiently generate ROS under white light irradiation and possess excellent killing effect on cancer cells. This study, thus, not only demonstrates applications in cell image-guided PDT cancer therapy performances but also provides strategy for construction of AIEgens with long emission wavelengths. © 2023 John Wiley & Sons, Ltd.

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. © 2023 The Authors. Published by American Chemical Society.

Despite advances in cancer therapy, the existence of self-renewing cancer stem cells (CSC) can lead to tumor recurrence and radiation resistance, resulting in treatment failure and high mortality in patients. To address this issue, a near-infrared (NIR) laser-induced synergistic therapeutic platform has been developed by incorporating aggregation-induced emission (AIE)-active phototheranostic agents and sulfur dioxide (SO2) prodrug into a biocompatible hydrogel, namely TBH, to suppress malignant CSC growth. Outstanding hydroxyl radical (& BULL;OH) generation and photothermal effect of the AIE phototheranostic agent actualizes Type I photodynamic therapy (PDT) and photothermal therapy through 660 nm NIR laser irradiation. Meanwhile, a large amount of SO2 is released from the SO2 prodrug in thermo-sensitive TBH gel, which depletes upregulated glutathione in CSC and consequentially promotes & BULL;OH generation for PDT enhancement. Thus, the resulting TBH hydrogel can diminish CSC under 660 nm laser irradiation and finally restrain tumor recurrence after radiotherapy (RT). In comparison, the tumor in the mice that were only treated with RT relapsed rapidly. These findings reveal a double-boosting & BULL;OH generation protocol, and the synergistic combination of AIE-mediated PDT and gas therapy provides a novel strategy for inhibiting CSC growth and cancer recurrence after RT, which presents great potential for clinical treatment.

The combination of cancer cell-activated fluorescence and the advantages of both type I and type II photodynamic therapy (PDT) capabilities to achieve a synergistic therapeutic effect in a complex tumor environment is highly desirable. Herein, we report an approach by means of tumor intracellular hypochlorite (ClO−) to turn on fluorescence integrated with type I and II ROS generation for imaging-guided PDT. The resultant PTZSPy functions as a type II photosensitizer with mitochondria-targeting capability. In the presence of ClO−, PTZSPy is transformed into its oxidized counterpart SPTZSPy, turns on an orange-red fluorescence and triggers the type I ROS generation ability. Biological studies revealed that PTZSPy can accurately distinguishes tumor cells from normal cells, dynamically monitors the cell ablation process and be utilized for theranostics in MCF-7 tumor-bearing nude mice in vivo. This work provides an innovative strategy exploiting the highly abundant ClO− in tumor cells for the type I and II ROS two-pronged and imaging-guided PDT. © 2023

Functional materials with multi-responsive properties and good controllability are highly desired for developing bioinspired and intelligent multifunctional systems. Although some chromic molecules have been developed, it is still challenging to realize in situ multicolor fluorescence changes based on a single luminogen. Herein, we reported an aggregation-induced emission (AIE) luminogen called CPVCM, which can undergo a specific amination with primary amines to trigger luminescence change and photoarrangement under UV irradiation at the same active site. Detailed mechanistic insights were carried out to illustrate the reactivity and reaction pathways. Accordingly, multiple-colored images, a quick response code with dynamic colors, and an all-round information encryption system were demonstrated to show the properties of multiple controls and responses. It is believed that this work not only provides a strategy to develop multiresponsive luminogens but also develops an information encryption system based on luminescent materials.

Kasha’s rule, which states that all exciton emissions occur from the lowest excited state and are independent of excitation energy, makes high-energy excitons difficult to use and severely hinders the widespread applications of organic photoluminescent materials in the real world. For decades, scientists have tried to break this rule to unleash the power of high-energy excitons, but only minimal progress has been achieved, with no rational guiding principles provided, and few applications developed. So far, breaking Kasha’s rule has remained a purely academic concept. In this paper, we introduce a design principle for a purely organic anti-Kasha system and synthesise a series of compounds based on the design rule. As predicted, these compounds all display evident S2emissions in dilute solutions. In addition, we introduce a highly accurate (over 90%) convolutional neural network as an assistant for the classification of cells using anti-Kasha luminogens, thereby providing a new application direction for anti-Kasha systems.

The development of new polymerization routes to afford N-heterocyclic polymers is of vital importance and highly desired for various practical applications. Herein, a facile and efficient polyannulation reaction of dual-activated alkyne and pyridines was developed to construct novel N-heterocyclic poly(quinolizine)s. This polymerization can proceed smoothly under catalyst-free conditions with 100% atom utilization to furnish poly(quinolizine)s with high molecular weights (up to 34,100) and well-defined structures in acceptable yields. The resulting polymers show good solubility, high thermal stability and strong red emission. Moreover, the prepared poly(quinolizine)s exhibit low cytotoxicity and can selectively label lysosomes in live cells. Considering the remarkable advantages of readily available raw materials, mild polymerization conditions, atom economy, and excellent product performance, this new and efficient polymerization tool will open up enormous opportunities for preparing functional N-heterocyclic polymers. [Figure not available: see fulltext.] © 2022, Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.

Microviscosity is a fundamental parameter in the biophysics of life science and governs numerous cellular processes. Thus, the development of real-time quantitative monitoring of microviscosity inside cells is important. The traditional probes for detecting microviscosity via time-resolved luminescence imaging (TRLI) are generally disturbed by autofluorescence or surrounding oxygen in cells. Herein, we developed loose packing nanoaggregates with aggregation-induced delayed fluorescence (FKP-POA and FKP-PTA) and free from the effect of oxygen and autofluorescence for viscosity mapping via TRLI. The feasibility of FKP-PTA nanoparticles (NPs) for microviscosity mapping through TRLI was demonstrated by monitoring the variation of microviscosity inside HepG2 cancer cells, which demonstrated a value change from 14.9 cP to 216.9 cP during the apoptosis. This indicates that FKP-PTA NP can be used as a probe for cellular microviscosity mapping to help people to understand the physiologically dynamic microenvironment. The present results are expected to promote the advancement of diagnostic and therapeutic methods to cope with related diseases. © 2022 American Chemical Society.

Electronic conjugation through covalent bonds is generally considered as the basis for the electronic transition of organic luminescent materials. Tetraphenylethylene (TPE), an efficient fluorophore with aggregation-induced emission character, fluoresces blue emission in the aggregate state, and such photoluminescence is always ascribed to the through-bond conjugation (TBC) among the four phenyl rings and the central C= C bond. However, in this work, systematic spectroscopic studies and DFT theoretical simulation reveal that the intramolecular through-space interaction (TSI) between two vicinal phenyl rings generates the bright blue emission in TPE but not the TBC effect. Furthermore, the evaluation of excited-state decay dynamics suggests the significance of photoinduced isomerization in the nonradiative decay of TPE in the solution state. More importantly, different from the traditional qualitative description for TSI, the quantitative elucidation of the TSI is realized through the atoms-in-molecules analysis; meanwhile, a theoretical solid-state model for TPE and other multirotor systems for studying the electronic configuration is preliminarily established. The mechanistic model of TSI delineated in this work provides a new strategy to design luminescent materials beyond the traditional theory of TBC and expands the quantum understanding of molecular behavior to the aggregate level.

Chirality is important to chemistry, biology and optoelectronic materials. The study on chirality has lasted for more than 170 years since its discovery. Recently, chiral materials with aggregation-induced emission (AIE) have attracted increasing interest because of their fascinating photophysical properties. In this review, we discussed the recent development of chiral materials with AIE properties, including their molecular structures, self-assembly and functions. Generally, the most effective strategy to design a chiral AIE luminogen (AIEgen) is to attach a chiral scaffold to an AIE-active fluorophore through covalent bonds. Moreover, some propeller-like or shell-like AIEgens without chiral units exhibit latent chirality upon mirror image symmetry breaking. The chirality of achiral AIEgens can also be induced by some optically active molecules through non-covalent interactions. The introduction of an AIE unit into chiral materials can enhance the efficiency of their circularly polarized luminescence (CPL) in the solid state and the dissymmetric factors of their helical architectures formed through self-assembly. Thus, highly efficient circularly polarized organic light-emitting diodes (CPOLEDs) with AIE characteristics are developed and show great potential in 3D displays. Chiral AIEgens are also widely utilized as “turn on” sensors for rapid enantioselective determination of chiral reagents. It is anticipated that the present review can entice readers to realize the importance of chirality and attract much more chemists to contribute their efforts to chirality and AIE study.

Owing to high sensitivity, selectivity, and non-invasiveness, fluorescence has been widely applied in the biomedical and sensing fields. Among the pool of fluorescent probes, luminogens with aggregation-induced emission (AIE) characteristic exhibit unique strengths in biological applications. However, most reported AIE luminogens (AIEgens) require complicated synthetic procedures, which raise the costs and biocompatibility concerns, especially in biomedical imaging and therapy. In contrast, bioproduct-inspired AIEgens (BioAIEgens) can compensate for the weakness of synthetic AIEgens in terms of their high biocompatibility, low costs, and easy preparation. This review highlights the latest development of BioAIEgens discovered from natural herbs, as well as their potential biomedical and sensing applications. As nature is full of potential resources, studying AIEgens from natural herbs can facilitate the strength of AIE properties in diverse applications and offer more inspiration to the future BioAIEgen structural design and development. © 2022 Elsevier Ltd

The discriminative detection of glutathione (GSH) from cysteine (Cys) remains a challenge because of their similarity in structure and chemical properties. This study reported a strategy for selective and sensitive detection of GSH based on the GSH-promoted blue fluorescence of UiO-66-NH2 and aggregation-enhanced emission (AEE) feature of orange emissive Cu nanoclusters (NCs). A relatively weak blue fluorescence of UiO-66-NH2 was converted to strong after reacting with GSH due to the rotation-restricted emission enhancement mechanism. In addition, the GSH-activated UiO-66-NH2 was further used as a template and reducing reagent for synthesizing orange-red AEE active Cu NCs composites (UiO-66-NH2@Cu NCs). A ratiometric fluorescence response was observed after forming UiO-66-NH2@Cu NCs, helping discriminate GSH over Cys. In addition, UiO-66-NH2@Cu NCs were further utilized for the detection of GSH in clinical samples. The present findings provide an efficient strategy to discriminate GSH over Cys and open a new door for utilizing and functionalizing metal-organic frameworks (MOFs) for various applications. © 2022 Elsevier B.V.

Materials showing metallophilic interactions continue to attract considerable theoretical and experimental attention largely because of their unusual and unanticipated photophysical behavior as well as their unique stimuli-responsive behavior in an aggregate or solid state. Metallophilic interactions are mostly found between metals with either identical (d10–d10) or different (s2–d8, d8–d10) configurations. Among various metallophilic interactions, aurophilic interactions (Au⋯Au) are well-known and widely reported. In this study, a new phosphorescent gold(I) complex, [(CF3Ph)3PAuC≡CPh] (TPPGPA) was reported. The crystal structure of TPPGPA demonstrated the formation of trimers caused by intermolecular aurophilic interactions. These trimeric crystals showed an efficient and nearly pure white-light emission with Commission Internationale de L’Eclairage 1931 chromaticity coordinates of (0.33, 0.34) at ambient conditions. Moreover, TPPGPA displayed fascinating mechanochromic and thermochromic luminescence properties in the crystalline state. The application of TPPGPA in temperature-responsive white-light illumination was also successfully demonstrated. The molecular packing and temperature-dependent modulation of the aurophilic interactions were subtly taken as a functional relationship of the experimental correlation with emission wavelength and intensity. It is anticipated that the present results will provide new insights into aurophilic interactions and provide a molecular design strategy for the construction of intelligent and stimuli-responsive gold(I) complex-based luminescent materials.

Bacterial keratitis (BK) is one of the most commonly leading causes of visual impairment and blindness worldwide, and suffers the risk of drug-resistant infections due to the abuse of antibiotics. Herein, we report a cationic diphenyl luminogen with aggregation-induced emission called IQ-Cm containing isoquinolinium and coumarin units for theranostic study of BK. IQ-Cm has no obvious cytotoxicity to mammalian cells below a certain concentration, and could preferentially bind to bacteria over mammalian cells. IQ-Cm can be used as a sensitive self-reporting probe to rapidly discriminate live and dead bacteria by the visual emission colors. The intrinsic dark toxicity to bacteria and generation of reactive oxygen species under light irradiation endow IQ-Cm with excellent antibacterial activity in vitro and in BK rabbit models infected with S. aureus. The present study provides a sensitive and efficient theranostic strategy for rapid discrimination of various bacterial states and the combined treatment of BK based on the intrinsic dark antibacterial activity and photodynamic therapy effect. © 2021

Stemming from unique ring structures, heterocyclic polymers exhibit distinguished electrical, mechanical, and photophysical properties and have been widely used in a variety of important applications. Along with the technological significance are the challenges in their synthesis. Traditional synthetic strategies toward heterocyclic polymers often require the direct attachment of heterocycles to polymer backbones, which are generally limited by the lack of suitable and low-cost heterocyclic monomers, tedious reaction process, difficulties in incorporation of multiple substitutents, etc. Alternatively, in situ construction of heterocyclic polymers via triple-bond based polymerization offers promising prospects. This review summarized the recent progress on polymerizations of triple-bond based monomers including alkynes, nitriles, and isonitriles that can in situ generate heterocyclic polymers. The properties and advanced applications of the derived heterocyclic polymers will also be discussed. Finally, the future perspectives and challenges in this field will be addressed. © 2021 Wiley-VCH GmbH

Cancer is one of the most severe diseases and is challenging human health and longevity. Cancer diagnosis is extremely important to improve the survival rate of patients. Cancer tissues/cells have been characterized with four distinctive biological features that significantly differ from normal tissues/cells, including higher vascular permeability, specific microenvironments of acidic pH, high reducibility and hypoxia, higher mitochondrial membrane potential, and overexpressed proteins. Therefore, accurate cancer discrimination can be achieved by targeting these characteristics. Currently, various imaging modalities have been developed to discriminate cancerous tissues/cells. Amongst, fluorescent technology has dominated the central position because it can directly, in-situ and real-time visualize and distinguish cancer tissues/cells at nano-micrometer resolution. Since its first discovery in 2001, aggregation-induced emission (AIE) has developed as a promissing and powerful fluorescent technique. Fluorogens with AIE characteristics (AIEgens) are non-emissive in molecular state, but show enhanced emission in aggregated state due to its restriction of intramolecular motion. Besides, AIEgens can work at high concentrations without considering the aggregation-caused quenching effect encountered by conventional organic fluorescent dyes. Given their unique superiorities, AIE-based fluorescent imaging technologies have emerged as appealing alternatives to traditional ones and obtained wide-ranging uses in cancer discrimination. Thus, herein we provide a comprehensive review of the recent progress of AIEgen-based fluorescent probes for cancer discrimination. These fluorescent probes can be classified into four categories, corresponding to four characteristics of cancer. The design strategies and working mechanisms for these probes and their applications for cancer bioimaging were highlighted and the pros and cons of these probes were criticized. Ultimately, this review wil

Microscopic control of macroscopic phenomena is one of the core subjects in materials science. Particularly, the spatio-temporal control of material behaviors through a non-contact way is of fundamental importance but is difficult to accomplish. Herein, a strategy to realize remote spatio-temporal control of luminescence behaviors is reported. A multi-arm salicylaldehyde benzoylhydrazone-based aggregation-induced emission luminogen (AIEgen)/metal-ion system, of which the fluorescence can be gated by the UV irradiation with time dependency, is developed. By changing the metal-ion species, the fluorescence emission and the intensity can also be tuned. The mechanism of the UV-mediated fluorescence change is investigated, and it is revealed that a phototriggered aggregation-induced emission (PTAIE) process contributes to the behaviors. The AIEgen is further covalently integrated into a polymeric network and the formed gel/metal-ion system can achieve laser-mediated mask-free writing enabled by the PTAIE process. Moreover, by further taking advantage of the time-dependent self-healing property of hydrazone-based dynamic covalent bond, transformable 4D soft patterns are generated. The findings and the strategy increase the ways to manipulate molecules on the supramolecule or aggregate level. They also show opportunities for the development of controllable smart materials and expand the scope of the materials in advanced optoelectronic applications. © 2021 Wiley-VCH GmbH

Chirality is important to chemistry, biology and optoelectronic materials. The study on chirality has lasted for more than 170 years since its discovery. Recently, chiral materials with aggregation-induced emission (AIE) have attracted increasing interest because of their fascinating photophysical properties. In this review, we discussed the recent development of chiral materials with AIE properties, including their molecular structures, self-assembly and functions. Generally, the most effective strategy to design a chiral AIE luminogen (AIEgen) is to attach a chiral scaffold to an AIE-active fluorophore through covalent bonds. Moreover, some propeller-like or shell-like AIEgens without chiral units exhibit latent chirality upon mirror image symmetry breaking. The chirality of achiral AIEgens can also be induced by some optically active molecules through non-covalent interactions. The introduction of an AIE unit into chiral materials can enhance the efficiency of their circularly polarized luminescence (CPL) in the solid state and the dissymmetric factors of their helical architectures formed through self-assembly. Thus, highly efficient circularly polarized organic light-emitting diodes (CPOLEDs) with AIE characteristics are developed and show great potential in 3D displays. Chiral AIEgens are also widely utilized as “turn on” sensors for rapid enantioselective determination of chiral reagents. It is anticipated that the present review can entice readers to realize the importance of chirality and attract much more chemists to contribute their efforts to chirality and AIE study.

Nitric oxide (NO) is an important signaling molecule overexpressed in many diseases, thus the development of NO-activatable probes is of vital significance for monitoring related diseases. However, sensitive photoacoustic (PA) probes for detecting NO-associated complicated diseases (e.g., encephalitis), have yet to be developed. Herein, we report a NO-activated PA probe for in vivo detection of encephalitis by tuning the molecular geometry and energy transformation processes. A strong donor-acceptor structure with increased conjugation can be obtained after NO treatment, along with the active intramolecular motion, significantly boosting “turn-on” near-infrared PA property. The molecular probe exhibits high specificity and sensitivity towards NO over interfering reactive species. The probe is capable of detecting and differentiating encephalitis in different severities with high spatiotemporal resolution. This work will inspire more insights into the development of high-performing activatable PA probes for advanced diagnosis by making full use of intramolecular motion and energy transformation processes.

Silkworm silk is a promising natural biopolymer for textile and biomedical applications for its remarkable flexibility, excellent biocompatibility and controllable biodegradability. The functionalization of silks makes them more versatile for flexible displays and visible bioscaffolds. However, fluorescent silks are normally fabricated through unstable physical absorption or complicated chemical reactions under harsh conditions. Herein, we developed a simple strategy for preparing fluorescent silks. Five aggregation‐induced emission luminogens (AIEgens) with activated alkynes were synthesized by rational molecular design, and then reacted with silk fibers through facile metal‐free click bioconjugation. The resulting conjugates show bright full‐color emissions and high stability. A white light‐emitting silk was fabricated by simultaneous bioconjugation with red‐, green‐ and blue‐emissive AIEgens. The red‐emissive AIEgen‐functionalized silks were successfully applied for long‐term cell tracking and two‐photon bioimaging, demonstrating great potential for tissue engineering and bioscaffold monitoring.

The emergence of the concept of aggregation-induced emission (AIE) has opened new opportunities in many research areas, such as biopsy analysis, biological processes monitoring, and elucidation of key physiological and pathological behaviors. As a new class of luminescent materials, AIE luminogens (AIEgens) possess many prominent advantages such as tunable molecular structures, high molar absorptivity, high brightness, large Stokes shift, excellent photostability, and good biocompatibility. The past two decades have witnessed a dramatic growth of research interest in AIE, and many AIE-based bioprobes with excellent performance have been widely explored in biomedical fields. This review summarizes some of the latest advancements of AIE molecular probes and AIE nanoparticles (NPs) with regards to biomedical and healthcare applications. According to the research areas, the review is divided into five sections, which are imaging and identification of cells and bacteria, photodynamic therapy, multimodal theranostics, deep tissue imaging, and fluorescence-guided surgery. The challenges and future opportunities of AIE materials in the advanced biomedical fields are briefly discussed. In perspective, the AIE-based bioprobes play vital roles in the exploration of advanced bioapplications for the ultimate goal of addressing more healthcare issues by integrating various cutting-edge modalities and techniques. © 2021 Wiley-VCH GmbH

Herein we report a linear ionic molecule that assembles into a supramolecular nano-tunnel structure through synergy of trident-type ionic interactions and π–π stacking interactions. The nano-tunnel crystal exhibits anisotropic guest adsorption behavior. The material shows good thermal stability and undergoes multi-stage single-crystal-to-single-crystal phase transformations to a nonporous structure on heating. The material exhibits a remarkable chemical stability under both acidic and basic conditions, which is rarely observed in supramolecular organic frameworks and is often related to structures with designed hydrogen-bonding interactions. Because of the high polarity of the tunnels, this molecular crystal also shows a large CO2-adsorption capacity while excluding other gases at ambient temperature, leading to high CO2/CH4 selectivity. Aggregation-induced emission of the molecules gives the bulk crystals vapochromic properties. © 2020 Wiley-VCH GmbH

Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation‐induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far‐red/near‐infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three‐pronged PDT.