AIE Nanoparticles Research Articles

Enhancement of Growth and Lipid Production in Microalgae Using Aggregation-Induced Emission Based Luminescent Material for Sustainable Food and Fuel.

AIEbased nanomaterials are progressively gaining momentum owing to their evolvement into an interdisciplinary field ranging from biomass and biomolecule yield to image-guided photodynamic therapy. This study focuses on a novel strategy to enhance growth, lipid accumulation, and in vivo fluorescence visualisation in green microalgae Chlamydomonas reinhardtii using AIE nanoparticles to quantify radical changes. The absorption of AIE photosensitiser, TTMN was recorded from 420 to 570 nm with a peak at 500 nm, and the emission ranged from 550 to 800 nm with a peak at 650 nm. As a ROSmolecule, H2O2 generation of TTMN in C. reinhardtii cells was detected with AIE nanoprobes TPE-BO. H2O2 accumulation increased with the increase of TTMN concentrations. The maximum growth was observed at 10 µM TTMN-exposed C. reinhardtii cells. Significant lipid accumulation was found in both 10 and 15 µM TTMN-treated cells. For lipid visualisation, an AIE nanoprobe, 2-DPAN was used, and superior fluorescence was determined and compared with the traditional BODIPY dye. Cytotoxicity analysis of 10 µM TTMN on the HaCat cell line with 86.2% cell viability revealed its high biocompatibility on living cells. This AIE-based nanotechnology provides a novel approach for microalgae-derived sustainable biomass and eco-friendly biofuel production.

A New Theranostic Platform Against Gram-Positive Bacteria Based on Near-Infrared-Emissive Aggregation-Induced Emission Nanoparticles.

Infections induced by Gram-positive bacteria pose a great threat to public health. Antibiotic therapy, as the first chosen strategy against Gram-positive bacteria, is inevitably associated with antibiotic resistance selection. Novel therapeutic strategies for the discrimination and inactivation of Gram-positive bacteria are thus needed. Here, a specific type of aggregation-induced emission luminogen (AIEgen) with near-infrared fluorescence emission as a novel antibiotic-free therapeutic strategy against Gram-positive bacteria is proposed. With the combination of a positively charged group into a highly twisted architecture, self-assembled AIEgens (AIE nanoparticles (NPs)) at a relatively low concentration (5µm) exhibited specific binding and photothermal effect against living Gram-positive bacteria both in vitro and in vivo. Moreover, toxicity assays demonstrated excellent biocompatibility of AIE NPs at this concentration. All these properties make the AIE NPs as a novel generation of theranostic platform for combating Gram-positive bacteria and highlight their promising potential for in vivo tracing of such bacteria.

Advancing fluorescence imaging with dual-mode AIE nanoparticles

Advancing fluorescence imaging with dual-mode AIE nanoparticles

Engineered Microglia‐Exosomes Coated Highly Twisting AIE Photothermal Agents to Efficiently Cross Blood‐Brain‐Barrier for Mild Photothermal‐Immune Checkpoint Blockade Therapy in Glioblastoma

AbstractImmune checkpoint blockade (ICB) therapy has achieved remarkable therapeutic effects in cancer, but it is not effective in glioblastoma (GBM). The main reason is that it is difficult for drugs to penetrate blood‐brain‐barrier (BBB) to GBM and lacks enough pre‐existing cytotoxic CD8+ T cells in GBM microenvironment. Here, two AIE photothermal agents (Fs and Fo) are synthesized with NIR‐II fluorescence emission and increase molecular twisting of AIE photothermal agents by simply changing one O atom into S atom, improving Fs photothermal conversion efficiency to 48%. Subsequently, engineered microglia‐exosomes AIE nanoparticles (EE@Fs‐NPs) are prepared by encapsulating Fs with microglia‐exosomes which express immune checkpoint LAG3 inhibitory antibody (anti‐LAG3) via genetic engineering technology. Engineered microglia‐exosomes endow that EE@Fs‐NPs cross BBB and target GBM, which successfully deliver anti‐LAG3 to GBM. Anti‐LAG3 highly reverses T cells exhaustion and generates TNF‐α for inhibiting the expression of heat shock proteins to enhance tumor cells thermosensitivity. Moreover, AIE photothermal agents of EE@Fs‐NPs generate mild photothermal therapy to destroy tumor cells and improve the infiltration of cytotoxic CD8+ T cells in GBM, which increases the responsiveness of ICB therapy. EE@Fs‐NPs produce powerful mild photothermal‐immune synergistic therapeutic effect, which will provide a therapeutic platform for the efficient treatment of GBM.

Time-resolved fluorescence imaging with color-changing, “turn-on/turn-on” AIE nanoparticles

Time-resolved fluorescence imaging with color-changing, “turn-on/turn-on” AIE nanoparticles

Biomimetic Approach toward Kinetically Stable AIE-Gens under Physiological Conditions.

Many AIE-gens suffer from excessive hydrophobicity, and their kinetic stability in aqueous condition is not warranted. Here, we introduce phosphorylcholine, a zwitterionic group ubiquitously found in biological membranes, onto the tetraphenylethene core structure to yield AIE nanoparticles stable in both PBS buffer and cell culture. We also find that the AIE efficiency is critically reliant on the delicate balance between the hydrophilic phosphorylcholine and hydrophobic moieties.

Donor–Acceptor–Donor Near-Infrared-II Aggregation-Induced Emission Luminogens (AIEgens) Encapsulated within Nanometer-Sized Exosomes for Tumor Imaging

Developing organic aggregation-induced emission luminogens (AIEgens) with a donor–acceptor–donor (D–A–D) structure improves fluorescence imaging for biological applications due to their deep tissue penetration, high fluorescence quantum yield, and good biocompatibility. However, compared to the systematically well-explored near-infrared-I (NIR-I, 650–900 nm) AIEgens, the research on organic D–A–D-type near-infrared-II (NIR-II, 1000–1700 nm) AIEgens received a snub, by contrast, owing to their lack of diversity, low AIE character, and poor tumor accumulation, which has become a bottleneck in the bioimaging field. Herein, we report a D–A–D-type organic NIR-II fluorophore with typical AIE character (αAIE > 4) through careful manipulation of the electron donor and acceptor. The tumor-associated macrophage (TAM)-derived exosomes with nanometer size were used as templates to encapsulate the NIR-II AIEgens (oBBT-DPNA) in a well-defined structure (named as AIE@Exo). The AIE@Exo displayed a superb aggregation-intensified NIR-II fluorescence with a maximum emission peak at 1052 nm as well as a calculated fluorescence quantum yield (QY) of 3.1%. Moreover, the in vivo application of AIE@Exo in efficient NIR-II fluorescence imaging of whole-body vessels and tumor was successfully demonstrated in living mice. Overall, the nanometer-sized biomimetic nanoparticles represent successful NIR-II AIE nanoparticles for biomedical imaging.

Preparation of Ultrasmall AIE Nanoparticles with Tunable Molecular Packing via Freeze Assembly

Advances in the development of aggregation-induced emission luminogens (AIEgens) depend on understanding how the molecular packing affects their luminescent properties and on making nanoparticles (NPs) with desired sizes. Although reported strategies have advanced the field, rational control of molecular packing and efficient fabrication of AIEgen NPs sub-5.5 nm in diameter remain pressing issues. Here we report a "freeze assembly" strategy, in which the diameter of AIEgen NPs can be precisely tuned from ∼3 nm to hundreds of nanometers, and a molecular packing in kinetically trapped states that are not easily captured by conventional assembly methods can be obtained, leading to tunable fluorescence emissions. Therefore, this study provides a significant tool to fabricate organic luminescent nanomaterials with diameters smaller than 5 nm, which is of critical importance for biomedical applications; meanwhile, tuning molecular packing in nanoparticles displaying different fluorescence may help to shed new light on the mechanism of AIEgens.

High-performance green-emitting AIE nanoparticles for lateral flow immunoassay applications.

Ultrabright green-emissive AIE nanoparticles (AIENPs) were used as signal-amplification probes to enhance the detectability of lateral flow immunoassay (LFIA). The detection performances of the green-emissive AIENP probes in both sandwich and competitive LFIA formats were systematically evaluated. Benefiting from its remarkable fluorescent brightness, the developed AIENP-LFIA showed versatile applicability for the detection of small molecules and macromolecules by using ochratoxin A (OTA) and procalcitonin (PCT) as model analytes, respectively. Under the optimum conditions, the detection limits (LODs) of the fabricated AIENP-LFIA for OTA and PCT were 0.043 ng mL-1 and 0.019 ng mL-1, respectively. These LOD values are significantly lower than those of conventional LFIA methods using gold nanoparticles as signal reporters. In addition, we demonstrated the practical application potential of AIENP-LFIA for the detection of OTA in real maize samples and PCT in real serum samples. These results indicated that the ultrabright green-emissive AIENPs were promising as signal output materials for building high-performance LFIA platform and broadening the application scenarios of LFIA.

Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility

AbstractAggregation‐induced emission (AIE) materials offer promising perspectives in disease diagnosis and therapeutics given their unique optical and photochemical properties. A key step toward translational applications for AIE materials is to systematically and vigorously evaluate their biosafety and biocompatibility. While previous studies focus on cellular viability and toxicity, the impact of AIE materials on detailed stress responses manifesting cellular fitness has been less explored. Herein, this work provides the first piece of evidence to support amphiphilic functionalization of AIE nanoparticles minimizes the deterioration on proteome stability and cellular protein homeostasis (proteostasis). To this end, four scaffolds of AIE molecules were prepared, further functionalized into eight nanoparticles with two amphiphilic shells respectively, and characterized for their physicochemical properties. Thermal shift assay quantitatively demonstrates that AIE materials after amphiphilic functionalization into nanoparticles enhance proteome thermodynamic stability and ameliorate proteome aggregation propensity in cellular lysate, echoed by cell viability and fractionation experiments. Intriguingly, poor polydispersity index (PDI) of functionalized nanoparticles exaggerates their retention and aggregation in the cell. Comparative proteomic analysis uncovers that amphiphilic functionalization of AIE materials can minimize the deterioration of cellular protein homeostasis network. Finally, vigorous interrogation of functionalized AIE nanoparticles in mice model reveals the complexity of factors affecting the biocompatibility profiles in vivo, including materials’ size, PDI, and treatment frequencies. Overall, amphiphilic functionalization of AIE materials into nanoparticles is necessary to maintain proteome stability and balance cellular protein homeostasis.

Antibacterial and Fluorescence Staining Properties of an Innovative GTR Membrane Containing 45S5BGs and AIE Molecules In Vitro.

This study aimed to add two functional components—antibacterial 45S5BGs particles and AIE nanoparticles (TPE-NIM+) with bioprobe characteristics—to the guided tissue regeneration (GTR) membrane, to optimize the performance. The PLGA/BG/TPE-NIM+ membrane was synthesized. The static water contact angle, morphologies, and surface element analysis of the membrane were then characterized. In vitro biocompatibility was tested with MC3T3-E1 cells using CCK-8 assay, and antibacterial property was evaluated with Streptococcus mutans and Porphyromonas gingivalis by the LIVE/DEAD bacterial staining and dilution plating procedure. The fluorescence staining of bacteria was observed by Laser Scanning Confocal Microscope. The results showed that the average water contact angle was 46°. In the cytotoxicity test, except for the positive control group, there was no significant difference among the groups (p > 0.05). The antibacterial effect in the PLGA/BG/TPE-NIM+ group was significantly (p < 0.01), while the sterilization rate was 99.99%, better than that in the PLGA/BG group (98.62%) (p < 0.01). Confocal images showed that the membrane efficiently distinguished G+ bacteria from G− bacteria. This study demonstrated that the PLGA/BG/TPE-NIM+ membrane showed good biocompatibility, efficient sterilization performance, and surface mineralization ability and could be used to detect pathogens in a simple, fast, and wash-free protocol.

AIE-nanoparticle assisted ultra-deep three-photon microscopy in thein vivomouse brain under 1300 nm excitation

Here we present organic AIE nanoparticles that feature high absorption cross-section under NIR-IIa three-photon excitation, which enables ultra-deep three-photon fluorescence imaging in thein vivomouse brain.

Nucleic acids induced peptide-based AIE nanoparticles for fast cell imaging

Herein, we utilized nucleic acids induced peptide co-assembly strategy to develop novel nucleic acids induced peptide-based AIE (NIP-AIE) nanoparticles. Strong fluorescent of AIE could be observed when a little amount of nucleic acids was added into the peptide solution, and the intensity could be regulated by the concentration of nucleic acids. This AIE nanoparticle with good biocompatibility could achieve fast cell imaging. It is also proved that the fluorescence intensity of AIE decreased with time, which indicates that the reducible cross-linkers of Wpc peptide by GSH and nanoparticles gradually disintegrate in cell. Based on the different of AIE fluorescence signals which regulated by the formation and disintegration of nanoparticles, this AIE system is expected to be used for real-time monitoring of drug release from peptide-based nano carriers in vivo or in vitro, and may provide a new platform for the construction of other organic AIE nanoparticles.

Self-assembled AIEgen nanoparticles for multiscale NIR-II vascular imaging

In the recent decades, fluorogens with aggregation-induced emission (AIEgens) have been intensively explored in biomedical applications. One main strategy to bring these hydrophobic AIEgens into the aqueous biological environment is to encapsulate them in nanoparticles with functionalized polymeric matrices. However, exploration of reliable strategies that can afford AIE nanoparticles with uniform size and stable loading efficiency with minimized variation still remains a challenge. Here, we rationally designed amphiphilic AIEgens, constructed by a hydrophobic donor-acceptor-donor (D-A-D) core and hydrophilic polyethylene glycol (PEG) chain. The afforded amphiphilic AIEgens can self-assemble into uniform nanoparticles with average sizes of ~35 nm, showing an emission maximum beyond 1000 nm and quantum yields (QYs) above 10%. We then used the bright AIE nanoparticles for multiscale intravital vascular fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) in mouse and rabbit models with a high-resolution of ~38 μm and a penetration depth of ~1 cm. As such, our results demonstrate an efficient self-assembly strategy to construct advanced AIE nanoparticles for angiography.

Real-time and noninvasive tracking of injectable hydrogel degradation using functionalized AIE nanoparticles

Abstract Visually monitoring of the residual morphology and quantitatively determining the degradation degree of hydrogels applied in tissue repair therapy in a real-time and noninvasive manner were a crucial technological mean. Despite conventional organic fluorescent molecules commonly used as probe to capture the real-time clues of the labeled hydrogels, they still encounter obstacles, including intrinsic photobleaching, cytotoxicity, and unknown interference factor of degradation caused by the change from polymer structure of hydrogels, thus making it difficult to accurately obtain the information of the hydrogels in vivo. To address the hard nut, we designed the multifunctional hydrogel system with a real-time quantitative aggregation-induced emission fluorescent detection and photoacoustic imaging tracking based on tetraphenylethene (TPE) that possesses the trait of aggregation-induced emission and low photobleaching, bound on the surface of mesoporous dopamine microspheres (MPDAs), and subsequently loaded into the photo-crosslinked injectable hydrogels. In vitro results showed that MPDA-TPE had good compatibility, emitted strong fluorescence when embedded in hydrogels, and maintained stable fluorescence property unless the hydrogels were degraded. Meanwhile, a mathematical formula for the kinetic degradation of hydrogels was established between gravitational and visual degradation in vitro, which can be used to predict in vivo degradation. Furthermore, MPDA possessed the clear photoacoustic imaging effect to provide more accurate clues. The designed hydrogel system holds a potential role in prediction of the in vivo degradation of implanted materials in an accurate, convenient, and real-time noninvasive manner and is a meaningful treatment aid in tissue engineering.

Dragonfly-shaped near-infrared AIEgen with optimal fluorescence brightness for precise image-guided cancer surgery

Organic near-infrared (NIR) emitters with simultaneously high absorption coefficient and photoluminescence quantum yield (PLQY) are highly desirable for biomedical imaging yet seldom reported because these two aspects are usually contradictory. The conjugated planar structures exhibit strong absorption but the emission is seriously quenched in aggregate state, whereas the twisted unplanar molecules display opposite phenomena. Herein, we report a kind of dragonfly-shaped NIR aggregation-induced emission luminogen (AIEgen) with both high absorption coefficient (6.24 × 104 M−1 cm−1) and superior PLQY (51.2%) for precise image-guided cancer surgery. The compound possessing a conjugated structure with vibrational substitutes has been synthesized, in which the good conjugation enables strong absorption, and the molecular vibration affords AIE signature. Moreover, the nonfluorescent processes are significantly suppressed, making every effort to boost fluorescence. The highly bright and stable AIE nanoparticles warrant efficient in vitro cellular imaging and in vivo tumor imaging. Moreover, the fluorescence imaging-guided cancer surgery helps to precisely delineate tiny tumor nodules, significantly improving the cancer surgery outcome. This work will inspire more insights into the development of organic NIR emitters with high brightness for biomedical applications.

Bright red aggregation-induced emission nanoparticles for multifunctional applications in cancer therapy.

Developing multifunctional photosensitizers (PSs) is needed to effectively simplify cancer treatment, but it remains a big challenge. Here, two red-emitting AIE-active, donor–acceptor (D–A) PSs with small ΔEST and their AIE nanoparticles, are rationally designed and synthesized. The PS1 NPs exhibit bright red-emission with high quantum yield, appropriate 1O2 generation ability and good biocompatibility. More importantly, PS1 NPs can strongly light up the cytoplasm by gently shaking the cells for only 5 s at room temperature, indicating ultrafast staining and mild incubation conditions. In vitro and in vivo cell tracing demonstrate that PS1 NPs can track cells over 14 days, and effectively inhibit tumor growth upon irradiation. To the best of our knowledge, this work is the first example of a PS that integrates image-guided PDT, ultrafast staining and long-term tracing functions, demonstrating the “all-in-one” concept which offers great advantages for potential clinical applications.

Tuning aggregation-induced emission nanoparticle properties under thin film formation

The preparation of AIE nanoparticles under thin film formation controls their size and the associated fluorescent intensity, with the smaller nanoparticles significantly increasing brightness.

Target-responsive AIE-Au nanoconjugate for acetylcholinesterase activity and inhibitor assay with ultralow background noise

Fluorescence nanosensor with ultralow fluorescence background is in highly demand for enhancing the sensing performance. Herein, we report a kind of nonfluorescent nanoconjugates between aggregation induced emission nanoparticles and gold nanoparticles (denoted as AIE-Au nanoconjugates) through electrostatic interaction, and further implement them in sensitive analysis of acetylcholinesterase (AChE) activity and inhibitors. Acetylthiocholine (ATCh) was effectively catalyzed by AChE and subsequently hydrolysized into thiocholine, which interacted with AuNPs via the relatively strong Au-S bonds leading to the separation of AIE nanoparticles and AuNPs to recover AIE nanoparticles’ fluorescence. Further, the proposed biosensor provided an ultrahigh sensitivity of 0.015 mU/mL for AChE. In view of the fact that AChE activity can be prohibited by inhibitors, AIE-Au nanoconjugates can also be applied for carbaryl analysis. On account of the exceptional properties, the prepared AIE-Au nanoconjugates broaden the perspectives of AIE nanoparticles and AuNPs for biosensor development, and demonstrated significant application prospect in food safety.

Precise design and synthesis of an AIE fluorophore with near-infrared emission for cellular bioimaging

Organic fluorophores emerge as important stains for bioimaging and biosensing, especially for fluorophores with aggregation-induced emission characters. However, the development of organic fluorophores with efficient AIE properties expand to far-red and/or near-infrared is still a great challenge. Herein, we precisely design and synthesize a novel D-π-A type of near-infrared AIE fluorophore (TPE-PTZ-R) by introducing phenothiazine (PTZ) to modify the typical AIE unit (tetraphenylethylene, TPE). TPE-PTZ-R displays good optical properties including a large Stokes shift and typical AIE properties. We next fabricate the uniform and stable AIE nanoparticles by loading Pluronic F127 and apply it in cellular bioimaging with high uptake efficiency, low cytotoxicity and good photostability.