Synthesis of Carbon Dots from Peltophorum Pterocarpum Flowers for Selective Fluorescence Detection of Carbendazim.

In this study, carbon dots (CDs) were synthesized from Peltophorum pterocarpum flowers as the precursor material using the hydrothermal method. The fluorescence emission spectra of the resulting Peltophorum pterocarpum CDs (PP-CDs) exhibited excitation-independent behavior, showing the fluorescence emission peak at 410 nm when excited at 330 nm. This method is simple, rapid and well consistent with the green chemistry and sustainable analytical method development. The as-synthesized PP-CDs acted as a promising fluorescent probe for detecting carbendazim (CBZ) via aggregation-induced emission mechanism, showing a linear response to CBZ concentrations ranging from 1 to 30 µM, with a detection limit of 5.41 nM. This method was successfully applied to quantify CBZ in food samples, achieving excellent recoveries of 99% with a relative standard deviation (RSD) of less than 2%.

A Membrane-Anchoring Self-Assembling Peptide Allows Bioorthogonal Coupling of Type-I AIEgens for Pyroptosis-Induced Cancer Therapy.

Enrichment of photosensitizers (PSs) on cancer cell membranes via bioorthogonal reactions is considered to be a very promising therapeutic modality. However, azide-modified sugars-based metabolic labeling processes usually lack targeting and the labeling speed is relatively slow. Moreover, it has been rarely reported that membrane-anchoring pure type-I PSs can induce cancer cell pyroptosis. Here, we report an alkaline phosphatase (ALP) and cholecystokinin-2 receptor (CCK2R) dual-targeting peptide named DBCO-pYCCK6, which can selectively and rapidly self-assemble on cancer cell membrane, and then bioorthogonal enrich type-I aggregation-induced emission luminogens (AIEgen) PSs (SAIE-N3) on the cell membrane. Upon light irradiation, the membrane-anchoring SAIE-N3 could effectively generate type-I reactive oxygen species (ROS) to induce gasdermin E (GSDME)-mediated pyroptosis. In vivo experiments demonstrated that the bioorthogonal combination strategy of peptide and AIEgen PSs could significantly inhibit tumor growth, which is accompanied by CD8+ cytotoxic T cell infiltration. This work provides a novel self-assembly peptide-mediated bioorthogonal reaction strategy to bridge the supramolecular self-assembly and AIE field through strain-promoted azide-alkyne cycloaddition (SPAAC) and elucidates that pure type-I membrane-anchoring PSs can be used for cancer therapy via GSDME-mediated pyroptosis.

Functionalized α-Cyanostilbene Derivatives for Detection of Hypoxia or Proteostasis Imbalance in Live Cells.

α-Cyanostilbene represents one of the easily functionalized aggregation-induced emission (AIE) scaffolds. It has been widely adopted for the construction of fluorescent materials for broad applications. Here, we further expanded the utilization of α-cyanostilbene derivatives for the detection of hypoxia or proteostasis imbalance in live cells. Four different amine containing donors were introduced to construct α-cyanostilbene derivatives (R-ASC) with donor-acceptor scaffolds. Equipped with the cysteine (Cys) reactive group, maleimide (MI), R-ASC-MI shows fluorescence turn-on property upon binding with unfolded proteins in vitro and in live cells under proteostatic stress. By virtue of R-ASC-MI, the level of unfolded protein loads in cells can be quantified by flow cytometry, or visualized under microscope. Furthermore, we also characterized the performance of R-ASC-NO2, synthetic precursors of R-ASC-MI, in cellular hypoxia. R-ASC-NO2 revealed upregulated activities of nitroreductase, as well as increased hydrophobicity in live cells, under either chemical (NaN3) induced or atmospheric (1% O2) hypoxia. Together, the advantages of easy modification and high signal-to-noise ratio of new α-cyanostilbene derivatives reported in this work highlight the great potential of α-cyanostilbene in constructing functional biosensors and many other domains.

Redox interference-free bimodal paraoxon sensing enabled by an aggregation-induced emission nanozyme catalytically hydrolyzing phosphoesters specifically.

In view of the current serious situation of organophosphorus pesticides (OPs) residue contamination, developing rapid and accurate OPs sensors is a matter of urgency. Redox-nanozyme based colorimetric sensors have been widely researched and utilized in OPs residue determination, but overcoming the interference of external redox substances and the effect of single-signal modes on detection performance is still a challenge. Here we fabricated a Zr-based metal-organic framework (MOF) featuring specific phosphatase-like activity and strong aggregation-induced emission (AIE) fluorescence for redox interference-free bimodal pesticide sensing. In the MOF, the activity-tunable Zr4+ node offered high hydrolytic activity and affinity toward P-O containing substrates, and the rigid framework structure effectively enhanced the fluorescence emission of the ligand 1,1,2,2-tetra(4-carboxylphenyl)ethylene. The developed AIEzyme could efficiently catalyze the hydrolysis of paraoxon to yellow p-nitrophenol, which further reduced the intrinsic AIE fluorescence of AIEzyme through internal filtration effect. Thereby, a natural enzyme-free dual-mode colorimetric/fluorescence approach was established for paraoxon detection with no interference from redox substances, and a smartphone-assisted portable platform was further developed to enable the facile, rapid, and high-performance sensing of the pesticide in complex practical matrices.

Biomimetic androgen receptor-based AIE biosensor for detecting bisphenol analogues: An integrating in silico topological analysis, molecular docking, and experimental validation study.

Bisphenol analogues are the typical class of endocrine disrupting chemicals (EDCs) that interfere with binding of endogenous hormones to androgen receptor (AR). With the expansion of industrial activities and the intensification of environmental pollution, an increasing array of bisphenol analogues is being released into the environment and food chain. This highlights the urgency to develop sensitive methods for the detection of bisphenol analogues. Here, we propose a biomimetic AR-based biosensor platform for detecting bisphenol analogues (BPF, TBBPA, and TBBPS) by binding with Aggregation-Induced Emission (AIE) probes. Following a comparison of the PROSS and ABACUS methods, biomimetic AR was designed using the ABACUS approach and subsequently expressed in vitro via the E. coli expression system. Through molecular docking and the observation of fluorescence changes upon binding with biomimetic AR, BS-46006 was selected as the AIE probe for the biosensor. The biomimetic AR-based biosensor showed sensitive detections of BPF, TBBPA, and TBBPS within a range of 0-50 mM. To further elucidate the multi-residue recognition mechanism, molecular orbitals, Electron Localization Function (ELF), and Localized Orbital Locator (LOL) were systematically calculated in this study. Lowest unoccupied molecular orbital and highest occupied molecular orbital indicated the energy gap of BPF, TBBPA, and TBBPS, which correspond to 0.12812, 0.19689, and 0.18711 eV, respectively. ELF and LOL offered clearer perspective through heat maps to visually represent the electron delocalization in BPF, TBBPA, and TBBPS. The matrix effect analysis suggested that the responses of bisphenol analogues in soil matrices could be effectively mitigated through sample pretreatment. The analysis of spiked soil samples showed the acceptable recoveries ranged from 91 % to 105 %. Additionally, the biomimetic AR-based AIE biosensor, which combines multi-residue detection with Tolerable Daily Intakes, shows great promise for the risk assessment of bisphenol analogues. This research may present a viable approach for the analysis of environmental pollutants.

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.

Development of Controllable Hetero-Pauson-Khand Polymerization to Functional Stimuli-Responsive Poly(γ-lactam)s.

Polymers containing lactam structures play a crucial role in both natural biological systems and human life, and their synthesis, functions and applications are of utmost importance for biomimetics and the creation of new materials. In this study, we developed an efficient heterogeneous Pauson-Khand polymerization (h-PKP) method for the controlled synthesis of main-chain poly(γ-lactam)s containing α, ß-unsaturated γ-lactam functionalities using readily available internal alkynes and imines. The molecular weights of the resulting poly(N-Ts/γ-lactam)s can be precisely controlled by adjusting the ratio of phenyl formate and nickel. These polymers exhibit high solid-state luminescence and demonstrate rapid and sensitive dual responsiveness to light and acid stimuli. They further demonstrate strong reactive oxygen species (ROS) generation capability. The unique dual-emission peaks observed in poly(N-H/γ-lactam)s obtained through post-treatment under acidic conditions demonstrate a mechanism of aggregation-induced intermolecular excited-state proton transfer specific to lactam structures. The efficient one-pot synthetic method for poly(γ-lactam) provides a novel strategy for constructing polymers with γ-lactam structures in the main chain and the simple and efficient post-modification method offer a versatile toolbox for functionalizing poly(γ-lactam)s to expand their potential applications.

A relay-type innate immunity activation strategy involving water-soluble NIR-II AIEgen for boosted tumor photo-immunotherapy.

Background: Effective innate immunity activation could dramatically improve the anti-tumor efficacy and increase the beneficiary population of immunotherapy. However, the anti-tumor effect of unimodal immunotherapy is still not satisfactory. Methods: Herein, a novel relay-type innate immunity activation strategy based on photo-immunotherapy mediated by a water-soluble aggregation-induced emission luminogen, PEG420-TQ, with the assistant of toll-like receptor 7 (TLR-7) agonist, imiquimod (R837), was developed and constructed. Results: The strategy could promote tumor cells to undergo immunogenic cell death (ICD) induced by the well-designed PEG420-TQ@R837 (PTQ@R) nanoplatform under light irradiation, which in turn enhanced the infiltration of immune cells and the activation of innate immune cells to achieve the first innate immunity activation. The second innate immunity activation was subsequently achieved by drug delivery of R837 via apoptotic bodies (ApoBDs), further enhancing the anti-tumor activity of infiltrated immune cells. Conclusion: The strategy ultimately demonstrated robust innate immunity activation and achieved excellent performance against tumor growth and metastasis. The construction of the relay-type innate immunity activation strategy could provide a new idea for the application of immunotherapy in clinical trials.

Aggregation-induced emission-based competitive immunoassays for "signal-on" detection of proteins with multifunctional metal-organic frameworks as signal tags.

An aggregation-induced emission (AIE)-based strategy was proposed for fluorescence immunoassays of protein biomarkers using Cu-based metal-organic frameworks (Cu-MOFs) to load recombinant targets and enzymes for dual signal amplification. The immunosensing platform was built based on the sequestration and consumption of the substrates of pyrophosphate (PPi) ions by Cu-MOFs and enzymatic catalysis. The negatively charged PPi could trigger the aggregation of positively charged tetraphenylethene (TPE)-substituted pyridinium salt nanoparticles (TPE-Py NPs) by electrostatic interactions, lighting up the fluorescence due to the AIE phenomenon. The consumption of PPi by the captured Cu-MOFs through the Cu2+-PPi chelation interaction and ALP-enzymatic hydrolysis depressed the aggregation of TPE-Py NPs. Capture of the tested targets in samples by the antibodies on the plate surface could prevent the attachment of target/ALP-loaded Cu-MOFs due to the competitive immunoreactions. The "signal-on" competitive immunoassay was applied for the detection of procalcitonin (PCT) as the model analyte with a linear range of 0.01-10 pg/mL and a detection limit down to 8 pg/mL. The conceptual integration of AIE with enzymatic and MOFs-based dual signal amplification endowed fluorescence immunoassays with high sensitivity and selectivity. The surface modification of Cu-MOFs with hexahistine (His6)-tagged recombinant proteins through metal coordination interactions should be evaluable for the design of novel biosensors.

Aggregation-induced emission: Application in diagnosis and therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious health issue due to its low early diagnosis rate, resistance to chemotherapy, and poor five-year survival rate. Therefore, it is crucial to explore novel diagnostic and therapeutic approaches tailored to the characteristics of HCC. Aggregation-induced emission (AIE) is a phenomenon where the luminescence of certain molecules, typically non-luminescent or weakly luminescent in solution, is significantly enhanced upon aggregation. AIE has been extensively applied in bioimaging, biosensors, and therapy. Fluorophore materials based on AIE (AIEgens) have a wide range of application scenarios and potential for clinical translation. This review focuses on recent advances in AIE-based strategies for diagnosing and treating HCC. First, the specific functional mechanism of AIE is described. Next, we summarize recent progress in the application of AIE for multimodal imaging, biosensor detection, and phototherapy. Finally, prospects and challenges for the AIE-based application in the diagnosis and therapy of HCC are discussed.

An Innovative Aggregation-Induced Emission-Based NIR Fluorescent Probe for Visualizing Carboxylesterases in Living Cells, Zebrafish, and Tumor-Bearing Mice.

In the human body, carboxylesterases (CEs) play crucial roles in xenobiotic metabolism and lipid homeostasis. But abnormal expression of CEs is highly associated with some diseases, such as hyperlipidemia, diabetes, and liver cancer. Therefore, it is of great importance to develop an efficient tool for the accurate detection of CEs in living organisms. Herein, an innovative near-infrared (NIR) fluorescent probe, TTAP-AB, was designed for CE detection based on the aggregation-induced emission (AIE) mechanism. This probe exhibits rapid response (2 min), excellent sensitivity (limit of detection = 8.14 × 10-6 U/mL), and high selectivity to CEs. Additionally, owing to its good biocompatibility, the TTAP-AB probe enables the monitoring of dynamic changes in CE levels under drug-induced modulation in living cells and zebrafish. More importantly, the TTAP-AB probe was successfully employed to image liver tumors and assist in tumor resection through the real-time monitoring of CEs, indicating that TTAP-AB is promising to guide liver cancer surgery. Therefore, the TTAP-AB probe can not only enrich the strategies for CE detection in biological systems but also has great potential for some clinical imaging applications, including medical diagnosis, preclinical research, and imaging-guided surgery.

Donor-acceptor-donor type AIEgens based on thieno[3.4-c]pyrrole-4,6-dione: Synthesis, electropolymerization, and electrochromism.

Photoelectric functional materials with electrochemical reversible activity and fluorescence intensities have attracted significant interest due to their wide range of applications in optoelectronic devices. In this work, a series of photoresponsive and electroactive monomers based on thieno[3.4-c]pyrrole-4,6-dione (TPD) are synthesized and characterized. They possess planar geometry with smaller dihedral angles owing to the existence of a noncovalent conformation lock coming from the S atoms and the O atoms. Crystallographic, spectroscopic, and computational results reveal that the introduction of the TPD unit can endow the monomers with aggregation-induced emission (AIE), reduced energy levels, and increased electrochemical activity. The monomers were successfully polymerized through the electrochemical method, and the corresponding polymers displayed reversible electrochemical activity and stability. Moreover, polymer films based on 3,3-dimethyl-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine (ProE)-TPD have electrochromic properties in the near-infrared field with a high value of optical contrast ratio (∆T) of 27.1% at 1000 nm.

A Novel AIE-Active Salicylaldehyde-Schiff Base Probe with Carbazole Group for Al3+ Detection in Aqueous Solution.

A donor-acceptor Schiff-base fluorescent probe BKS with chelation enhanced fluorescence (CHEF) mechanism was designed and synthesized via benzophenone(Acceptor), salicylaldehyde and carbazole(Donor) for Al3+ detection, which exhibited typical aggregation-induced emission (AIE) characteristic. BKS probe could provide outstanding selectivity to Al3+ with a prominent fluorescence "turn-on" at 545 nm in a wide pH range from 2 to 11. By the Job's plot, the binding stoichiometry ratio of probe BKS to Al3+ was determined 1:1. The proposed strategy offered a very low limit of detection at 1.486 µM in THF/H2O(V/V = 1:4, HEPBS = 10 mM, pH = 7.40), which was significantly lower than the standard of WHO (Huang et al., Microchem J 151:104195, 2019)-(Yongjie Ding et al., Spectrochim Acta Mol Biomol Spectrosc 167:59-65, 2021) guidelines for drinking water. BKS probe could provide a wider linear detection range of 50 to 500 µM. Furthermore, the probe could hardly be interfered by other examined metal ions. The analysis of Al3+ in real water samples with appropriate recovery (100.72 to 102.85) with a relative standard deviation less than 2.82% indicated the accuracy and precision of BKS probe and the great potential in the environmental monitoring of Al3+.

Osmapentalenofurans Constructed by Reacting Os≡C1 of Osmapentalyne with Phenols.

Over the past decade, significant research efforts have focused on osmapentalyne, characterized by the more reactive Os≡C7 (Carbon atoms numbered in a clockwise direction on the osmapentalyne skeleton), across areas encompassing electrophilic, nucleophilic, and addition reactions. Nevertheless, the reactivity of osmapentalyne featuring Os≡C1 remains ripe for further exploration. In this investigation, we effectively synthesized a lineage of osmapentalenofurans through the nucleophilic reaction of osmapentalyne incorporating Os≡C1 with phenols. These resulting complexes demonstrate near-infrared luminescence traits in both solid and liquid states. Particularly noteworthy is the osmapentalenofuran derived from tetraphenylethane (TPE) unit, which showcases remarkable aggregation-induced emission ( AIE) property in the aggregated state. These osmapentalenofurans are also able to further extend their range of reactions, including reactions with base and isonitrile. This study not only broadens the scope of applications for metal aromatics but also furnishes valuable insights into the realm of specialized functional materials.

A fluorescent Aptasensor based on magnetic-separation strategy with gold nanoclusters for Deoxynivalenol (DON) detection.

A highly sensitive method based on MBs-cDNA@Apt-AuNCs519 was developed for deoxynivalenol (DON) detection in wheat. The MBs-cDNA@Apt-AuNCs519 was established using green emission gold nanoclusters (AuNCs519) with aggregation-induced emission properties as signal probes and combining amino-modified DON-aptamer (Apt), biotin-modified DNA strand (the partially complementary to Apt (cDNA)), and streptavidin-modified magnetic beads (MBs). The Apt-AuNCs519 were well connected with MBs-cDNA without DON but dissociated from MBs-cDNA@Apt-AuNCs519 with the addition of DON, leading to a noticeable reduction in the fluorescent intensity of the aptasensor. Moreover, this fluorescence aptasensor showed two linear relationships in the concentration range of 0.1-50 ng/mL and 50-5000 ng/mL with a limit of detection of 3.73 pg/mL with good stability, reproducibility and specificity. The results were consistent with high-performance liquid chromatography and enzyme-linked immunosorbent assay methods, further indicating the potential of this method for accurate trace detection of DON in wheat.

Micronano Lasers Based on Aggregation-Induced Emission Molecules: Diverse Resonant Cavities Investigation.

Aggregation-induced emission (AIE) molecules have great potential to enhance the performance of micronano lasers due to their excellent aggregated luminescence properties, so it is valuable to expand their applications in micronano lasers. In this work, a typical AIE active fluorescent dye motif 9,10-bis(2,2-diphenylvinyl) anthracene (BDPVA) was selected as the gain medium. First, drop-casting was used to fabricate BDPVA single-crystal nanowires, which can be used as Fabry-Perot (FP)-type resonators with a lasing threshold of 49.4 µJ/cm2. Furthermore, we innovatively doped BDPVA molecules as gain mediums into external polymer Whispering-Gallery-Mode (WGM)-type resonators via the emulsion self-assembly method. Fabricated BDPVA-doped polystyrene (PS) microspheres exhibit a much lower lasing threshold of 9.04 µJ/cm2. These results prove that the BDPVA molecules, in addition to realizing the reported AIE single-crystal lasers, can also be used as a guest-doped gain medium in the resonant cavity for obtaining better fluorescence gain. In addition, multimode tunability of two types of lasers has been successfully achieved by tuning the structure of the resonant cavity. This work further expands the application potential of AIE materials and will provide a useful reference for the rational design and fabrication of photonic micronano laser components using AIE materials.

Three-in-One: Molecular Engineering of D-A-π-A Featured Type I and Type II Near-Infrared AIE Photosensitizers for Efficient Photodynamic Cancer Therapy and Bacteria Killing.

Bacterial infections are closely correlated with the genesis and progression of cancer, and the elimination of cancer-related bacteria may improve the efficacy of cancer treatment. However, the combinatorial therapy that utilizes two or more chemodrugs will increase potential adverse effects. Image-guided photodynamic therapy is a highly precise and potential therapy to treat tumor and microbial infections. Herein, four donor-acceptor-π-bridge-acceptor (D-A-π-A) featured near-infrared (NIR) aggregation-induced emission luminogens (AIEgens) (TQTPy, TPQTPy, TQTC, and TPQTC) with type I and type II reaction oxygen species (ROS) generation capabilities are synthesized. Notably, TQTPy shows mitochondria targeted capacity, the best ROS production efficiency, long-term tumor retention capacity, and more importantly, the three-in-one fluorescence imaging guided therapy against both tumor and microbial infections. Both in vitro and in vivo results validate that TQTPy performs well in practical biomedical application in terms of NIR-fluorescence imaging-guided photodynamic cancer diagnosis and treatment. Moreover, the amphiphilic and positively charged TQTPy is able to specific and ultrafast discrimination and elimination of Gram-positive (G+) Staphylococcus aureus from Gram-negative (G-) Escherichia coli and normal cells. This investigation provides an instructive way for the construction of three-in-one treatment for image-guided photodynamic cancer therapy and bacteria elimination.

Room-Temperature Liquid Crystalline Tetraphenylethylene-Surfactant Complex with Chiral Supramolecular Structure and Tunable Circularly Polarized Luminescence.

A novel room-temperature liquid crystal of tetraphenylethylene derivative (TPE-DHAB) was synthesized using an ionic self-assembly strategy. The TPE-DHAB complex exhibits typical aggregation-induced emission properties and a unique helical supramolecular structure. Moreover, the generation and handedness inversion of circularly polarized luminescence (CPL) can be achieved through further chiral solvation, providing a facile approach to fabricate room-temperature liquid crystalline materials with controllable supramolecular structures and tunable CPL properties through a synergistic strategy of ionic self-assembly and chiral solvation process.

Novel thiomaleimide-based fluorescent probe with aggregation-induced emission for detecting H2S.

It has been well established that Hydrogen sulfide (H2S) is involved in various pathophysiological processes. Therefore, accurate monitoring H2S levels in vitro or vivo is of great significance in biological systems. Herein, we firstly developed a thiomaleimide-based compound MAL-1 bearing aggregation-induced emission characteristic for selective response toward H2S due to its nucleophilicity. The proposed sensor presented prominent sensitivity and selectivity with low detection limit of 75 nM and pseudo-first-order reaction rate constant of 9.65 × 10-2 s-1, as well as low cytotoxicity which works well in recognizing H2S in real samples and visualizing H2S in living cells. Thus, it could be concluded that the novel thiomaleimide-based probe would be a promising tool for assessing intracellular H2S levels.

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.