Aggregation-induced Emission Characteristics Research Articles

Multi-Functional AIE Phototheranostic Agent Enhancing αPD-L1 Response for Oral Squamous Cell Carcinoma Immunotherapy.

Oral squamous cell carcinoma (OSCC) represents a prevalent head and neck malignancy with surgical intervention as the primary clinical option. Immunotherapy, particularly immune checkpoint blockade (ICB) targeting PD-1/PD-L1 shows great promise but is impeded by the immunosuppressive tumor microenvironment and low PD-L1 expression in OSCC. Herein, the "all-in-one" phototherapeutic nanoparticles (TSD NPs) are reported with balanced reactive oxygen species and photothermal conversion capacity for combined photoimmunotherapy and ICB immunotherapy against OSCC. A novel electron acceptor, 3-(dicyanomethylene)-2,3-dihydrobenzothiophene-1,1-dioxide (DTM), is introduced to develop the phototherapeutic agent with aggregation-induced emission (AIE) feature and NIR-II fluorescence centered at 1000nm. Benefiting from the AIE feature and the DTM acceptor, the resultant TSD NPs also exhibit strong type I reactive oxygen species (ROS) generation and high photothermal conversion efficiency (45.3%), which can profoundly induce immunogenic cell death (ICD), activate cytotoxic T lymphocytes, and convert the immunosuppressive tumor microenvironment into an immune-supportive one. Additionally, TSD NPs upregulate the PD-L1 expression on OSCC cells, thus enhancing the efficacy of combined treatment with αPD-L1 ICB immunotherapy. This results show that the synergistic treatment of TSD NPs and αPD-L1 effectively eradicates solid OSCC tumors without adverse effects on normal tissues, proving a novel and promising strategy for OSCC management.

Mitochondria-Targeting AIEgens as Pyroptosis Inducers for Boosting Type-I Photodynamic Therapy of Tongue Squamous Cell Carcinoma.

The development of a photosensitizer (PS) that induces pyroptosis could be a star for photodynamic therapy (PDT), particularly with type-I PSs that produce reactive oxygen species (ROS) in a hypoxic tumor microenvironment. Since pyroptosis is a recently characterized cell death pathway, it holds promise for advancing PDT in oncology, with PSs playing a critical role. Herein, we develop a PS named Th-M with aggregation-induced emission (AIE) characteristics for type-I PDT against tongue squamous cell carcinoma (TSCC). Th-M stands out for its exceptional mitochondrial-targeting ability, which triggers mitochondrial dysfunction and leads to Caspase-3 and Gasdermin E (GSDME) cleavage under white light irradiation, inducing pyroptosis in TSCC cells. Our studies verify the effectiveness of Th-M in destroying cancer cells in vitro and suppressing tumor growth in vivo while also demonstrating a favorable biosafety profile. This work pioneers the application of Th-M as a mitochondria-targeted, type-I PS that leverages the mechanism of pyroptosis, offering a potent approach for the treatment of TSSC with promising implications for future PDT of cancers.

A cell membrane-targeted photosensitizer for cancer photodynamic therapy and dynamic ablation process tracking

Photodynamic therapy (PDT) uses photosensitizer (PS) to generate reactive oxygen species (ROS) under light to trigger cell apoptosis in cancer treatment. Organelle-targeted PS can effectively enhance the efficacy of phototherapy by specifically destroying subcellular organelles. The cell membrane, as an important organelle, is the “protective wall” of cells maintaining the integrity and normal life activities of cells. The damage to cell membranes is fatal to cells. However, utilizing functional PS to achieve cell membrane-targeted PDT, and realize real-time and accurate in situ reporting of cell membrane damage and monitoring of the treatment process, are challenging tasks. In this work, we prepared a photosensitizer (2TPAO) with aggregation-induced emission (AIE) characteristics, good water solubility, strong near-infrared fluorescence, and the capability for specific imaging of cell membranes. Moreover, 2TPAO could effectively produce ROS under visible light irradiation and achieve photodynamic ablation of tumor cells and tumors. Meanwhile, during PDT, the fluorescence changes of 2TPAO indicated the destruction of cell membranes, allowing intuitive determination of the phototherapy results. Therefore, 2TPAO is an effective cell membrane-targeted PS for cancer PDT.

Expanding Our Horizons: AIE Materials in Bacterial Research.

Bacteria share a longstanding and complex relationship with humans, playing a role in protecting gut health and sustaining the ecosystem to cause infectious diseases and antibiotic resistance. Luminogenic materials that share aggregation-induced emission (AIE) characteristics have emerged as a versatile toolbox for bacterial studies through fluorescence visualization. Numerous research efforts highlight the superiority of AIE materials in this field. Recent advances in AIE materials in bacterial studies are categorized into four areas: understanding bacterial interactions, antibacterial strategies, diverse applications, and synergistic applications with bacteria. Initial research focuses on visualizing the unseen bacteria and progresses into developing strategies involving electrostatic interactions, amphiphilic AIE luminogens (AIEgens), and various AIE materials to enhance bacterial affinity. Recent progress in antibacterial strategies includes using photodynamic and photothermal therapies, bacterial toxicity studies, and combined therapies. Diverse applications from environmental disinfection to disease treatment, utilizing AIE materials in antibacterial coatings, bacterial sensors, wound healing materials, etc., are also provided. Finally, synergistic applications combining AIE materials with bacteria to achieve enhanced outcomes are explored. This review summarizes the developmental trend of AIE materials in bacterial studies and is expected to provide future research directions in advancing bacterial methodologies.

Study on mechanofluorochromism, ink-free writing, and latent fingerprint imaging of the functionalized difluoroboron compounds with methyl and methoxy

Two difluoroboron compounds including amide linkage moiety, compound F-1 with methoxy group and compound F-2 with methyl group, were designed and successfully synthesized. The results indicated that the solid powders of two compounds both displayed mechanofluorochromism phenomena, which originated from phase transformation between the well-ordered microcrystalline and amorphous states, and the intramolecular charge transfer, as well as the mechanofluorochromism of compound F-1 was better than that of compound F-2 due to larger dipole moment change value between the ground and excited states. Additionally, compound F-1 had more twisted molecular spatial conformation, which exhibited aggregation-induced emission in mixtures of THF/water, yet compound F-2 was observed aggregation-caused quenching phenomenon. It was gratified that two compounds had the potential application in the field of ink-free writing owing to their reversibly mechanofluorochromism behaviors, not only that, compound F-1 could be used to latent fingerprint imaging because of its aggregation-induced emission feature.

Assembly of protein-directed fluorescent gold nanoclusters for high-sensitivity detection of uranyl ions

Uranium is a key element in the nuclear industry, whose accidental release causes health and environmental problems. In this paper, a protein-directed fluorescent sensor with aggregation-induced emission characteristics (gold nanoclusters@ovalbumin, AuNCs@OVA) was synthesized for the detection of UO22+ with high sensitivity and selectivity. The sensor exhibited good fluorescence stability, and its fluorescence intensity could be selectively enhanced by UO22+. Based on FT-IR and XPS analyses, the increase in fluorescence intensity of AuNCs@OVA after the addition of UO22+ was attributed to aggregation induced by the complexation between UO22+ and the amino, carboxyl, hydroxyl, and phosphate groups of ovalbumin. The detection limit was determined to be 34.4 nM, and the sensor showed excellent ion selectivity for UO22+. In combination with a smartphone program, the sensor could realize the real-time detection of UO22+ in a quantitative and portable way.

Aggregation-Induced Emission Photosensitizer Boosting Algal Growth and Lipid Accumulation.

Mass production of microalgae is a research focus owing to their promising aspects for sustainable food, biofunctional compounds, nutraceuticals, and biofuel feedstock. This study uses a novel approach to enhance microalgae-derived biomass and metabolites by using an aggregation-induced emission (AIE) photosensitizer (PS), CN-TPAQ-PF6 ([C32H23N4]+). The unique AIE features of CN-TPAQ-PF6 facilitate nano-aggregation in aquatic media for an effective light spectral shift for photosynthetic augmentation in a green microalga, Chlamydomonas reinhardtii. The high reactive oxygen species (ROS) production capacity and redox-based cellular modulations reveal its potential to upsurge algal growth and lipid biosynthesis and fabricate fatty acid profiles in the metabolic pathways. Algal cells are labeled with other AIE-based nanoprobes, which are suitable as an in vivo visualization toolkit with superior fluorescence. Furthermore, cytotoxicity analysis of CN-TPAQ-PF6 on the HaCat cell line confirms that this AIE PS is biocompatible without adverse impact on living cells. The results demonstrate the property of AIE PS for the first time in enhancing algal growth and lipid accumulation simultaneously.

Exploring Cyclopentannulation as an Effective Synthetic Tool to Design Polycyclic Aromatic Hydrocarbon AIEgens for Bioimaging.

Synthesis of various polycyclic aromatic hydrocarbons (PAHs) from a palladium-catalyzed [3 + 2] cyclocondensation reaction is reported herein. The design strategy consisted of reacting the sterically hindered 1,2-bis(3,5-ditert-butylphenyl)acetylene 2 with myriad brominated anthracene and pyrene surrogates, resulting in the formation of target molecules MCP1-2 and DCP1-3, which exhibited excellent solubility in commonly used organic solvents and unveiled prominent aggregation-induced emission (AIE) characteristics in tetrahydrofuran and water solvent mixtures. Calculations using density functional theory (DFT) were utilized to validate both the contorted structures of the target molecules and their electronic conjugation featuring HOMO-LUMO band gaps (ΔE) in the range of ∼2.88 to 2.97 eV for the monocylopentannulated PAHs MCP1-2, and between ∼2.23 to 2.41 eV for the dicyclopentannulated PAHs DCP1-3. Furthermore, the biomedical features of DCP2 were investigated in cell-imaging experiments employing the RAW 264.7 macrophage cell line as a model system showing a high biocompatibility for DCP2, thus paving the way for its potential application in bioimaging. These findings underscore the significance of the target compounds as prominent AIEgens with exceptional photophysical properties and biocompatibility, therefore promoting them as valuable tools for bioimaging applications.

A long-wavelength fluorescent probe based on carbazole with AIE characteristics for the detection of ONOO− and its application

Peroxynitrite (ONOO−) is an important reactive oxygen species, and excess ONOO− in the body can lead to a range of diseases. Addressing the need for sensitive detection ONOO−, in this work, a highly sensitivity and selectivity long-wavelength fluorescent probe (named CIS) was designed for tracking ONOO− in biological cells. Probe CIS featured carbazole as the fluorophore and the CC double bond with two electron withdrawing –CN groups as the recognition site. The probe CIS exhibited the typical aggregation-induced emission (AIE) and intramolecular charge transfer (ICT) characteristics with the bright red fluorescent emission in high water fraction (fw ≥ 50 %) and negligible emission in low water fraction. The fluorescence emission wavelength of probe CIS is 631 nm, with a large Stokes shift (151 nm), which can sensitively detect ONOO− in DMSO: H2O (7:3, v/v) environment. Notably, the probe CIS exhibited a wide pH detection range (pH = 3–10), a low detection limit of 36.66 nM, high selectivity and minimal interference. Furthermore, probe CIS demonstrated excellent biocompatibility and low cytotoxicity, and can be used for the detection of exogenous ONOO− in 4T1 cells (Mouse breast cancer cells). These research results indicate that probe CIS has potential application prospects in the biological aspects.

Tumor targeting pH-triggered fluorescence-switchable hyaluronic acid-based micelles with aggregation-induced emission activity for tracing drug release and intelligent drug delivery

In this study, an amphiphilic polymer (Bio-HA(TPE-CN)-mPEG) was designed and synthesized, which was fabricated by introducing hydrophobic aggregation-induced emission (AIE) fluorophore, acid-labile imine bond, methoxy poly (ethylene glycol) (mPEG) and tumor targeting ligand biotin to the backbone of hyaluronic acid. The polymer could self-assemble into micelles and solubilize hydrophobic anticancer drugs. In vitro drug release study indicated that the micelles could disassemble rapidly under acidic environment. The involvement of biotin and HA could enhance the cellular uptake of micelles by tumor cells. Modification of micelles by mPEG could minimize non-specific protein adsorption. Fluorescence studies indicated that the micelles exhibited excellent AIE features and emitted intense long-wavelength fluorescence. More excitingly, the micelles were red emissive in the normal physiological environment, but switched to blue fluorescence in the acidic tumor environment, which could be further applied for real-time monitoring and quantification of the drug release. The in vivo antitumor efficacy study demonstrated the superior antitumor activity of the PTX-loaded micelles. The Bio-HA(TPE-CN)-mPEG micelles were promising drug carriers for chemotherapy and bioimaging.

Synergistic integration of a rhodamine-labelled tripeptide into AIE-active fluorogenic probe: Enabling nanomolar detection of Al3+ ions through test strips, thin films, and Arduino-assisted optosensing platform

Peptide-fluorophore conjugates (PFCs) have been expeditiously utilized for metal ion recognition owing to their distinctive characteristics. Selective detection and quantification of aluminum is essential to minimize health and environmental risks. Herein, we report the synthesis and characterization of a new chemoprobe with aggregation-induced emission characteristics by chemically conjugating rhodamine-B fluorophore with a tripeptide. The probe revealed β-sheet secondary conformation in both solid and solution states, as confirmed by FT-IR, PXRD, and CD experiments. AIE characteristics of the probe in water-MeCN mixtures revealed the formation of spherically shaped nanoaggregates with an average size of 353 ± 7 nm, as confirmed by SEM, TEM, and DLS studies. The probe exhibited a large stokes shift (175 nm) and displayed selective colorimetric and fluorometric responses towards Al3+ ions with an extremely low detection limit (51 nm) and a fast response time (≤15 s). Comparative NMR studies confirmed the cleavage of spirolactam ring upon aluminum binding. The probe’s practicality was enhanced through integration into test strips and thin films, allowing solid-phase detection of Al3+ ions. Furthermore, an RGB-Arduino enabled optosensing device has been developed to enable instant quantifiable analysis of aluminum concentrations in real-time conditions.

Preparation and Application of a Sulfur-Doped Fluorescent Carbon Dots with Aggregation-Induced Emission Character.

As a new type of zero-dimensional nanomaterial, carbon dots are widely applied in various fields. However, most of the carbon dots have aggregation fluorescence quenching properties, which limited their practical applications. In this study, a novel sulfur-doped carbon dots (S-CDs) was prepared by solvothermal method. The properties of the S-CDs in ethanol solution and in solid state were investigated respectively. The results showed that the S-CDs have an excited wavelength dependent emission of blue fluorescence in ethanol solution, and have orange fluorescence emission in solid state and composite films, indicating the prepared S-CDs has aggregation-induced emission (AIE) performance. The main reason was that the presence of S-S bonds and the intramolecular rotation of aromatic rings were limited in solid state, resulting in its emission of orange fluorescence. Furthermore, the S-CDs could be applied to identify fingerprints, anti-counterfeiting.

Aggregation-Induced Emission Phosphorescence Featured Au-Ag Coordination Polymer with a Diphosphine N-Heterocyclic Carbene Ligand for Highly Sensitive Detection of Cr(VI).

Luminescent materials with aggregation-induced emission (AIE) characteristics have been recognized as highly selective and sensitive probes for the detection of toxic metal ions in recent years. In this paper, a Au-Ag cluster-based coordination polymer [Au3Ag3(L)2(CN)6(H2O)2]n [1, L = 1,3-bis((diphenylphosphanyl)methyl)-4,5-dihydro-imidazolylidene] was prepared by in situ generation of the diphosphine N-heterocyclic carbene (PCNHCP)-type ligand L in the presence of the corresponding metal salts. Compound 1 exhibited 530 nm phosphorescence under 380 nm excitation with a QY of 6.30% and a lifetime (τ) of 7.14 μs in the solid state. 1 showed good AIE behavior in the mixture of MeOH/H2O while the best aggregation state (fwater = 90%, QY = 6.79%, τ = 6.70 μs) exhibited selective and sensitive emission quenching toward Cr(VI) ions. Ultralow detection limits of 9.7 ppb (w/w) for Cr2O72- and 17.9 ppb (w/w) for CrO42- were achieved.

Aggregative Luminescence from CsPbBr3 Perovskite Precursors.

Understanding the properties of the precursor can provide deeper insight into the crystallization and nucleation mechanisms of perovskites, which is vital for the solution-process device performance. Herein, we conducted a detailed investigation into the photophysics properties of CsPbBr3 precursors in a broad concentration and various solvents. The precursor transformed from the solution state into the colloidal state and exhibited aggregation-induced emission character as the concentration increased. The aggregative luminescence from the precursors originates from the polybromide plumbous that is formed through the coordination of solvent molecules to the lead metal center. Two adducts with monodentate (PbBr2 ⋅ solvent) and bidentate (PbBr2 ⋅ 2solvent) ligands can be obtained, accompanied by emission with photoluminescence at 610 and 565 nm, respectively. Furthermore, the aggregative luminescence intensity and color could be regulated by changing the solvent and precursor ratio. Besides, we discussed the difference between the molecular aggregate in the organic system and the ionic aggregate in the inorganic system: the ionic aggregate is composed of solvated ions rather than individual molecules as in organic systems, which could possess properties that ions do not have. The fluorescence that is sensitive to Pb2+ coordination reported here could be applied to screen perovskite additives and judge the precursor aging.

Synthesis and Aggregation-Induced Emission Properties of New Carbazole-Based Pyranones and their Ring Transformed Derivatives

A new series of N-phenyl-carbazole (N-phCbz) appended pyranones were designed and synthesized using α-oxo-ketene-S, S-acetal under mild reaction conditions in good yields. The reactivity of donor-acceptor (D-A)-based 2H-pyranones was utilised to develop their ring-transformed benzene-cored N-phenyl-carbazole derivatives. All the synthesised carbazole-based pyranones showed aggregation-induced emission (AIE) characteristics in 80-99% water fraction (fw) in DMSO. Among all the synthesized compounds, 6-(4-(9H-carbazol-9-yl)phenyl)-4-(methylthio)-2-oxo-2H-pyran-3-carbonitrile exhibited excellent AIE behaviour with ~70 fold increase in fluorescence in 80% fw at 550nm. Furthermore, this compound showed exceptionally high fluorescence in nonpolar solvent (THF) as compared to polar solvents like DMSO (~200-fold increase in fluorescence). The DFT, DSC and TGA analysis of the synthesised D--A compounds suggested the strong electron donor ability of N-phCbz, with good thermal stability in the range of 231-393 °C. These N-phenyl-carbazole-appended pyranones with interesting AIE properties have great potential as probes for bioimaging applications as well as for optoelectronic materials.

Endoplasmic reticulum-targeted fluorescent probe with aggregation-induced emission features for imaging peroxynitrite in drug-induced liver injury model

Drug-induced liver injury (DILI) poses a severe threat to public health. Endoplasmic reticulum (ER) stress contributes significantly to DILI pathogenesis, with peroxynitrite (ONOO−) identified as a pivotal indicator. However, the temporal and spatial fluctuations of ONOO− associated with ER stress in the pathogenesis of DILI remain unclear. Herein, a novel ER-specific near-infrared (NIR) probe (QM-ONOO) with aggregation-induced emission (AIE) features for monitoring ONOO− fluctuations in DILI was elaborately constructed. QM-ONOO exhibited excellent ER-targeting specificity, a large Stoke's shift, and a low detection limit (26.9 nM) toward ONOO−. QM-ONOO performed well in imaging both exogenous and endogenous ONOO− in HepG2 cells. Furthermore, molecular docking calculations validated the ER-targeting mechanism of QM-ONOO. Most importantly, using this probe allowed us to intuitively observe the dynamic fluctuations of ONOO− during the formation and remediation processes of DILI in the acetaminophen (APAP)-induced mouse model. Consequently, this work provides a promising tool for in-depth research of ONOO− associated pathological processes in DILI.

High-contrast tricolor-tunable solid luminescent AIE-active Au(I) isocyanide complexes based on thermo- and mechanochromism

Breaking through the limitations of traditional luminescent materials, integrating the charming aggregation-induced emission (AIE) characteristics, high-contrast mechanochromism and thermochromism into one molecule is of great significance to make stimuli-responsive materials more intelligent. Herein, two Au(I) isocyanide complexes with short alkoxyl chains (C2 and C3) in the solid state are designed and synthesized, the length of the alkoxyl chain exerts significant impacts on molecular arrangement. Both C2 and C3 exhibit obvious AIE properties, the green luminescent aggregate of C2 and C3 is result from J-aggregation while the orange luminescent aggregate of C3 is result from the formation of aurophilic bonds, which supported by the single crystal X-ray analysis. Moreover, C2 and C3 not only display red-shifted mechanochromism (20 nm and 26 nm), but also exhibit gradual blue-shifted thermochromism. A tricolored luminescent switch application was demonstrated using C3 as a multi-stimuli responsive material. This molecular design strategy provides a new avenue for efficient luminescent materials with AIE and multi-stimuli responsive properties.

Discovery of Fluorescent Naturally-occurring Inhibitor of SARS-CoV-2 Main Protease By AIE Fluorescent Probe.

Target-based high-throughput screening (HTS) is an efficient way to identify potent drugs. However, the accuracy of HTS could be affected by Pan-Assay Interference Compounds (PAINS). One reason for the generation of PAINS is that the inherent photophysical property of screened compounds could interfere with typically used assay signals including absorption and fluorescence. Our previous studies indicate that the fluorescent probe based on the fluorophore with characteristics of aggregation-induced emission (AIE) could provide high accuracy of HTS, especially for the fluorescent natural products. Herein, we report an AIE-based fluorescent probe for the main protease (Mpro) of SARS-CoV-2. We designed and synthesized an AIE fluorescent probe ZLHG5, which has a site that can be specifically cleaved by Mpro to produce a light-up fluorescence. Thanks to the large Stokes shift of AIE fluorophore (~300 nm), the probe could be effectively used for HTS of Mpro inhibitors. After screening a library of fluorescent natural products with ZLHG5, we obtained two coumarin-originated natural compounds with potent inhibitory activity towards Mpro protease. This study provides both useful fluorescent HTS probe and potent inhibitors for Mpro protease.

Thermally versatile maleimide-based polymeric thin film for detection and separation of picric acid from polluted areas

2,4,6-Trinitrophenol, commonly known as picric acid, is a powerful explosive that has been used historically in military ammunition. Picric acid is extremely toxic and sensitive to friction and heat; thus, it is prone to accidental detonation at high temperatures. It is critical to detect and separate picric acid from the impacted areas. In the present study, we designed and developed a fluorescent copolymer (P1) for temperature-dependent picric acid detection. The solvatochromic and aggregation-induced emission (AIE) properties of P1 were utilized to detect picric acid at a high temperature of 40 °C (high alert level) by turn-off emission. Additionally, a polymeric thin film (F1) was fabricated by immobilizing P1 onto the surface of quartz slide. Notably, F1 retained its emissive properties across a range of temperatures (both relatively low and high alert levels), facilitated by its AIE characteristics. The portable film, F1, displayed a nanomolar sensitivity toward picric acid, making it suitable for on-site detection in aqueous media (neutral pH). Furthermore, F1 demonstrated efficient separation of picric acid from nitroaromatic explosive mixtures with a separation efficiency of 70 % over four cycles. Importantly, F1 exhibited practical utility in detecting and separating picric acid in real samples, highlighting its potential for environmental monitoring applications.

Enhanced chemiluminescence resonance energy transfer using surfactant-modified AIE carbon dots.

Chemiluminescence resonance energy transfer (CRET) efficiency can be enhanced by confining CRET donors and acceptors within nanoscale spaces. However, this enhanced efficiency is often affected by uncertainties stemming from the random distribution of CRET donors and acceptors in such confined environments. In this study, a novel confined nanospace was created through the surfactant modification of carbon dots (CDs) exhibiting aggregation-induced emission (AIE) characteristics. Hydrophobic CRET donors could be effectively confined within this nanospace. The distance between the CRET donors and acceptors could be controlled by anchoring the AIE-CDs as the CRET acceptors, resulting in significantly improved CRET efficiency. Furthermore, this AIE-CDs-based CRET system was successfully applied to the detection of hydrogen peroxide (H2O2) in rainwater, showcasing its potential for practical applications.