Aggregation-induced Emission Fluorogen Research Articles

Fabrication of chitosan based luminescent nanoprobe with aggregation-induced emission feature through ultrasonic treatment

Chitosan is an abundant natural polysaccharide that contains a lot of amino and hydroxyl groups. It possesses great potential for biomedical applications owing to its low toxicity, biodegradability and low cost. Herein, a novel chitosan-based fluorescent copolymer (WS-CS-TPA) was designed and synthesized via nucleophilic substitution of hexachlorocyclotriphosphazene (HCCP), water-soluble chitosan (WS-CS) and an aggregation-induced emission (AIE) fluorogen (AIEgen) triphenylamine derivative (TPA-NH2). Under ultrasonic treatment, 1.16 g TPA-NH2 and 1.1 g WS-CS can be conjugated by 0.7 g HCCP at room temperature. The obtained copolymer shows amphiphilic property and could assemble into nanoparticles with size about 100 nm. After self-assembly, TPA-NH2 was aggregated in the core, thus exhibiting superb AIE feature with intense green fluorescence emission in aqueous media. On the other hand, hydrophilic WS-CS was coated on the surface of nanoparticles and endowed their high water dispersibility. Results from preliminary biological assays suggested that WS-CS-TPA can be internalized by cells and exhibits low cytotoxicity, suggesting their great potential for biological imaging and intracellular drug delivery.

Progress in glycosylated aggregation-induced emission materials

<p indent="0mm">Materials with aggregation-induced emission (AIE) effect have excellent optical properties and are widely utilized in chemical sensing, biological probes and other fields. Since most classic AIE fluorogens are hydrophobic, their application was restricted to some extent. In the past <sc>5 years</sc>, several glycosylated AIE-active fluorescent probes were synthesized by coupling the AIE cores with hydrophilic carbohydrates in our group and were used for detection of various biomolecules based on the special binding and reaction between these probes and analytes. These glycosylated AIE-active fluorescent probes with better water solubility and biocompatibility have low fluorescence background and low biological toxicity. This review summarized the recent progress on the glycosylated AIE-active fluorescent probes, hoping to expand the applications of AIE materials and provide effective tools for biochemistry research.

Developing Novel Fabrication and Optimisation Strategies on Aggregation-Induced Emission Nanoprobe/Polyvinyl Alcohol Hydrogels for Bio-Applications.

The current study describes a new technology, effective for readily preparing a fluorescent (FL) nanoprobe-based on hyperbranched polymer (HB) and aggregation-induced emission (AIE) fluorogen with high brightness to ultimately develop FL hydrogels. We prepared the AIE nanoprobe using a microfluidic platform to mix hyperbranched polymers (HB, generations 2, 3, and 4) with AIE (TPE-2BA) under shear stress and different rotation speeds (0–5 K RPM) and explored the FL properties of the AIE nanoprobe. Our results reveal that the use of HB generation 4 exhibits 30-times higher FL intensity compared to the AIE alone and is significantly brighter and more stable compared to those that are prepared using HB generations 3 and 2. In contrast to traditional methods, which are expensive and time-consuming and involve polymerization and post-functionalization to develop FL hyperbranched molecules, our proposed method offers a one-step method to prepare an AIE-HB nanoprobe with excellent FL characteristics. We employed the nanoprobe to fabricate fluorescent injectable bioadhesive gel and a hydrogel microchip based on polyvinyl alcohol (PVA). The addition of borax (50 mM) to the PVA + AIE nanoprobe results in the development of an injectable bioadhesive fluorescent gel with the ability to control AIEgen release for 300 min. When borax concentration increases two times (100 mM), the adhesion stress is more than two times bigger (7.1 mN/mm2) compared to that of gel alone (3.4 mN/mm2). Excellent dimensional stability and cell viability of the fluorescent microchip, along with its enhanced mechanical properties, proposes its potential applications in mechanobiology and understanding the impact of microstructure in cell studies.

Development and application of Diels-Alder adducts displaying AIE properties

Exploring organic reactions to construct novel molecules with aggregation-induced emission (AIE) features is an essential branch of AIE research. The fast-paced application of AIE materials in various disciplines, including photoelectricity, molecular biology, medicine, and materials science, has led to an ever-growing need for new AIE molecules. Unlike the synthesis of most “earlier generations” of AIE fluorogens (AIEgens) that require tedious and harsh reactions, chemists now shift their synthetic focus to a selection of reliable and straightforward reactions. The Diels-Alder reaction has been overlooked in this field. Herein, we report a catalyst-free Diels-Alder reaction between 1,3-diphenylisobenzofuran and a series of electron-deficient alkynes to create AIEgens. Photophysical properties of our synthesized 1,3,4-triphenyl-1,4-dihydro-1,4-epoxynaphthalene (ENAP) derivatives are studied systematically, manifesting their AIE characteristics and structure-fluorescence property relationships. Finally, we highlight the diverse applications of some selected ENAP derivatives in latent fingerprint detection, cell imaging, and bacterial staining.

Peptide-Conjugated Aggregation-Induced Emission Fluorogen: Precise and Firm Cell Membrane Labeling by Multiple Weak Interactions

Cell membrane is a vital barrier to protect the cell from outside damage and involved in many biochemical processes. It is of great significance to label the cell membrane to explore its function. ...

Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review

Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review

Construction of a Highly Sensitive Thiol-Reactive AIEgen-Peptide Conjugate for Monitoring Protein Unfolding and Aggregation in Cells.

Impairment of the protein quality control network leads to the accumulation of unfolded and aggregated proteins. Direct detection of unfolded protein accumulation in the cells may provide the possibility for early diagnosis of neurodegenerative diseases. Here a new platform based on a peptide-conjugated thiol-reactive aggregation-induced emission fluorogen (AIEgen), named MI-BTD-P (or D1), for labeling and tracking unfolded proteins in cells is reported. In vitro experiments with model proteins show that the non-fluorescent D1 only becomes highly fluorescent when reacted with the thiol group of free cysteine (Cys) residues on unfolded proteins but not glutathione or folded proteins with buried or surface exposed Cys. When the labeled unfolded proteins form aggregates, D1 fluorescence intensity is further increased, and fluorescence lifetime is prolonged. D1 is then used to measure unfolded protein loads in cells by flow cytometry and track the aggregate formation of the D1 labeled unfolded proteins using confocal microscopy. In combination with fluorescence lifetime imaging technique, the proteome at different folding statuses can be better differentiated, demonstrating the versatility of this new platform. The rational design of D1 demonstrates the outlook of incorporation of diverse functional groups to achieve maximal sensitivity and selectivity in biological samples.

Liposome-encapsulated aggregation-induced emission fluorogen assisted with portable smartphone for dynamically on-site imaging of residual tetracycline

Reliable on-site monitoring of antibiotic residue is critical to establish the efficient pollution early-warning mechanism for ensuring food safety and environmental health. Herein, we reported the engineering of liposome-encapsulated aggregation-induced emission fluorogen into the portable smartphone for achieving the visual on-site detection of residual tetracycline (TC). Through nanoprecipitation, the aggregation-induced emission fluorogen (AIEgen) tetraphenylethene (TPE) was encapsulated into an amphiphilic phospholipid polymer, affording a scaffold to assemble Eu3+ for forming Eu3+-functionalized liposome-based AIEgen (Eu3+@AIEgen) with bright blue fluorescence at ~456 nm. Upon assistance of citrate, TC was capable of triggering the remarkable fluorescence color change from bright blue (~456 nm) to pink owing to the new red fluorescence emission appeared at ~611 nm, thereby emerging a significant dual-emission for ratiometric response. As expected, an ingenious citrate-assisted Eu3+@AIEgen liposome-based smartphone was proposed to precisely on-site report the residual levels of TC in real sample among the linear range of 0.0961–10.0 μM. Furthermore, this portable sensor exhibited a high sensitivity attributable to the low detection limit of 28.83 nM together with a fast response kinetics of 2.0 min for TC, agreeing well with the demands of on-site assay. This study showed the promising potential for utilizing AIEgen liposome to develop a new category of portable sensors for the point-of-care detection of antibiotic residue in complicated food and environment-related matrixes, which might open a novel way to establish efficient pollution early-warning mechanism for safeguarding public health.

A cell membrane-anchored nanoassembly with self-reporting property for enhanced second near-infrared photothermal therapy

Tumor residues caused by limited light penetration depth and inadequate concentration of photothermal agents (PTAs) in photothermal therapy (PTT) easily result in the tumor recurrence and metastasis. In turn, treatment overdose would increase unavoidable damage to the nearby normal tissues. To solve this dilemma, we design a cell-membrane-anchored nanoassembly (designated as DTPRR9) for aggregation-induced emission fluorogens (AIEgens) imaging guided second near-infrared (NIR-II) PTT, which can not only achieve a higher therapeutic effect through locating and retaining on the tumor cell membrane, but also monitor the therapeutic feedback to avoid excessive phototoxicity. DTPRR9 nanoassemblies are obtained by co-encapsulating AIEgens and NIR-II absorbing semiconducting polymers via amphiphilic polymers, and then further modified with RR9 peptide (RGDRRRRRRRRRC). Under a 1064 nm laser irradiation, DTPRR9 with high photothermal conversion efficacy (η = 70.4%) could directly disrupt cell membrane by in situ generated hyperthermia. Moreover, the translocation of AIE fluorescence from the damaged cell membrane could be used to self-report the therapeutic effect. This cell-membrane-anchored nanoassembly brings an advanced strategy to surmount difficulties of low therapeutic efficiency and severe potential side effects in PTT.

Practicable Applications of Aggregation-Induced Emission with Biomedical Perspective.

Considerable efforts have been made into developing aggregation-induced emission fluorogens (AIEgens)-containing nano-therapeutic systems due to the excellent properties of AIEgens. Compared to other fluorescent molecules, AIEgens have advantages including low background, high signal-to-noise ratio, good sensitivity, and resistance to photobleaching, in addition to being exempt from concentration quenching or aggregation-caused quenching effects. The present review outlines the major developments in the biomedical applications of AIEgens-containing systems. From a literature survey, the recent AIE works are reviewed and the reasons why AIEgens are chosen in various biomedical applications are highlighted. The research activities on AIEgens-containing systems are increasing rapidly, therefore, the present review is timely.

AIE-active polymeric micelles based on modified chitosan for bioimaging-guided targeted delivery and controlled release of paclitaxel

In this study, a novel polymer based on aggregation-induced emission (AIE) fluorogen, biotin and disulfide bonds modified chitosan (TPE-bi(SS-CS-Bio)) was designed and synthesized. The polymer could self-assemble into micelles in aqueous media and encapsulate paclitaxel (PTX) into the core with high drug loading. Fluorescence study indicated that the micelles exhibited excellent AIE feature with intense blue fluorescence emitted. In vitro drug release study indicated that the micelles could disassemble rapidly in the presence of high level of glutathione. The modification by biotin could enhance the cellular uptake of the micelles. The drug-loaded micelles possessed remarkable cytotoxicity against MCF-7 cells, and their distribution in the cells could be traced due to the excellent AIE feature. In vivo antitumor efficacy study demonstrated the superior antitumor activity of the PTX-loaded TPE-bi(SS-CS-Bio) micelles. These results indicated that TPE-bi(SS-CS-Bio) has the ability of biological imaging and can be used as a potential carrier for PTX.

Highly Efficient Near-Infrared Photosensitizers with Aggregation-Induced Emission Characteristics: Rational Molecular Design and Photodynamic Cancer Cell Ablation.

Photosensitizers (PSs) that play a decisive role in effective photodynamic therapy (PDT) have attracted great research interest. PSs with aggregation-induced emission (AIE) characteristics could overcome the deficiencies of traditional PSs that usually suffer from the aggregation-caused fluorescence quenching (ACQ) effect in applications and show enhanced emission and high singlet oxygen (1O2) generation efficiency in aggregates; therefore, they are outstanding candidates for imaging-guided PDT, and the development of AIE PSs with both excellent photophysical properties and 1O2 generation ability is highly desirable. Herein, three AIE fluorogens (AIEgens), BtM, ThM, and NaM, with a donor-π-acceptor (D-π-A) structure were designed and synthesized, and the photosensitizing ability was adjusted by π-linker engineering. All of the three AIEgens showed excellent photostability and high molar absorption coefficients, and their emission edges were extended to the near-infrared (NIR) region, with peaks at 681, 678, and 638 nm, respectively. NaM demonstrated the smallest ΔES1-T1, which was ascribed to its better separation degree of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). The AIEgens were fabricated into nanoparticles (NPs) by amphipathic mPEG3000-DSPE encapsulating, and thus the obtained NaM NPs exhibited the best 1O2 generation efficiency under white light irradiation, which was almost 3 times that of the renowned PS rose bengal (RB). Furthermore, under white light irradiation, the cell killing efficiency of NaM NPs was also much better than those of the other two AIE PSs and RB. Therefore, NaM NPs revealed great potential to treat superficial diseases as a PS for PDT.

Hypoxia-Triggered In Situ Self-Assembly of a Charge Switchable Azo Polymer with AIEgens for Tumor Imaging.

In recent years, stimuli-responsive in situ self-assembly fluorescent probes for tumor imaging, which leverage the advantage of efficient penetrability and satisfactory accumulation, have attracted much attention. In this work, we rationally integrate charge switchable azobenzene moiety and long wavelength aggregation-induced emission fluorogens (AIEgens) into one water-soluble polymer to construct the hypoxia-triggered in situ self-assembly fluorescent probe for tumor imaging. Due to the good water solubility and the quenching effect of azobenzene moiety, the AIEgens containing polymer showed no significant fluorescence. Under a tumor hypoxic environment, the enzymatic reduction of azobenzene triggered cationic quaternary ammonium converting into anionic carboxylate. Then self-assembly nanoparticles were obtained, driven by the electrostatic interaction between negatively charged carboxylate ion and positively charged AIEgens, which emitted a strong orange-red fluorescence.

Fluorescent Sizing Agents Based on Aggregation-Induced Emission Effect for Accurate Evaluation of Permeability and Coating Property

Warp sizing is the most important process of weaving preparation in the textile industry. Permeating and coating of sizing paste into/on warp yarns directly determine the quality of sized yarns. However, there are many significant drawbacks, such as low accuracy and narrow variety adaptability for sizing agents and warp yarns, in the traditional determination method of permeation and coating property of sizing paste. Focusing on the problem, this investigation introduced aggregation-induced emission (AIE) fluorogen to prepare a fluorescent sizing agent. The interface of sizing agent in textile could be accurately visualized by AIE fluorogen. The three indexes to indicate the permeability and coating property of sizing paste, i.e. permeation percentage, coating percentage and integrity percentage of sizing film, have been determined accurately and conveniently. This investigation efficiently solves the difficult problem of evaluating permeation and coating property of sizing paste and has a significant guiding function on accurate determination of the quality of sized yarns.

Fulgide Derivative-Based Solid-State Reversible Fluorescent Switches for Advanced Optical Memory

Fulgide Derivative-Based Solid-State Reversible Fluorescent Switches for Advanced Optical Memory

Novel Imaging of Silver Nanoparticle Uptake by a Unicellular Alga and Trophic Transfer to Daphnia magna.

Widely applied silver nanoparticles (AgNPs) can have potentially detrimental impacts on aquatic organisms. Unicellular algae as primary producers can interact with AgNPs and initiate their transfer along food chains. Herein, we demonstrate that AgNPs were internalized in a freshwater phytoplankton species Chlamydomonas reinhardtii, but the entrance pathways varied with their surface coatings. Citrate-coated AgNPs (Cit-AgNPs) were internalized mainly through the apical zone of the cell near the flagella, whereas the aggregation-induced emission fluorogen (AIEgen)-coated AgNPs (AIE-AgNPs) were internalized through endocytosis. The internalized AgNPs were dissolved intracellularly and the released Ag+ was distributed heterogeneously in the cytoplasm, in contrast to the directly accumulated Ag+ which displayed a diffuse cytoplasmic distribution pattern. We then further visualized and quantified the trophic transfer of AgNPs from the alga C. reinhardtii to the zooplanktonic species Daphnia magna. Both trophically transferred Ag+ and AgNPs were concentrated in the gut regions of D. magna as a result of the direct ingestion of food particles. After ingestion, about 95% of the trophically transferred Ag+ was eliminated. Retention of AIE-AgNPs by daphnids was relatively higher than that of Cit-AgNPs due to their lower dissolution of Ag+. The present study provides direct evidence for the internalization of AgNPs in unicellular algae and demonstrates that the biological transport of trophically transferred of AgNPs is related to the different surface coatings of NPs.

Recent Advances in Two-Photon AIEgens and Their Application in Biological Systems.

Two-photon fluorescence imaging technology has the advantages of high light stability, little light damage, and high spatiotemporal resolution, which make it a powerful biological analysis method. However, due to the high concentration or aggregation state of traditional organic light-emitting molecules, the fluorescence intensity is easily reduced or disappears completely, and is not conducive to optimal application. The concept of aggregation-induced emission (AIE) provides a solution to the problem of aggregation-induced luminescence quenching (ACQ), and realizes the high fluorescence quantum yield of luminescent molecules in the aggregation state. In addition, two-photon absorption properties can readily be improved just by increasing the loading content of AIE fluorogen (AIEgen). Therefore, the design and preparation of two-photon fluorescence probes based on AIEgen to achieve high-efficiency fluorescence imaging in vitro/in vivo has become a major research hotspot. This review aims to summarize representative two-photon AIEgens based on triphenylamine, tetraphenylethene, quinoline, naphthalene and other new structures from the past five years, and discuss their great potential in bioimaging applications.

Twisted Intramolecular Charge Transfer—Aggregation-Induced Emission Fluorogen with Polymer Encapsulation-Enhanced Near-Infrared Emission for Bioimaging

Fluorescence probes with strong near-infrared (NIR) emission and water solubility are considered useful visualization tools for localization marking as well as investigating cell migration and tran...

Capturing protein droplets: label-free visualization and detection of protein liquid-liquid phase separation with an aggregation-induced emission fluorogen.

We developed a new method for protein droplet visualization by means of a droplet probe (DroProbe) based on an aggregation-induced emission (AIE) fluorogen. A simple method for viscosity comparison of the protein condensed phase based on the lifetime of the DroProbe was also developed.

Fluorescent Reporters for Antimicrobial Peptides

Antimicrobial peptides (AMPs), a part of the natural defence against pathogens, have been considered as alternative antibiotics to combat the increase of antimicrobial resistance (AMR). Given the advanced development of fluorescent probes, extensive research has been focussed on understanding the physiological processes of the interaction between AMPs and bacteria. To better guide the choice of suitable fluorescent reporters for the mechanism study of AMPs, in this review, we summarise a toolbox of commonly used fluorescent reporters for AMP studies, including intrinsic fluorescent reporters, conventional fluorophores, and recently developed aggregation-induced emission (AIE) fluorogens.