Rational design of a water-soluble NIR AIEgen, and its application in ultrafast wash-free cellular imaging and photodynamic cancer cell ablation.
ABSTRACT: The synthesis of water-soluble near-infrared (NIR)-emissive fluorescent molecules with aggregation-induced emission (AIE) characteristics and theranostic functions is highly desirable but remains challenging. In this work, we designed and readily prepared for the first time such a molecule with AIE features, good water-solubility and intense emission in the NIR region. This AIE luminogen (AIEgen) is able to specifically "light up" the cell membrane without the involvement of a washing procedure. Interestingly, the staining process can be performed by simply shaking the culture with cells at room temperature for only a few seconds after the addition of the AIEgen, indicating an ultrafast and easy-to-operate staining protocol. This is the first fluorescent "light-up" probe for cell-imaging that allows the combination of a short staining period (at the second-level) with a wash-free process. Additionally, the presented AIEgen has also been developed to serve as an excellent phototherapeutic agent for high efficiency generation of reactive oxygen species (ROS) upon visible light irradiation, which allows its effective application in the photodynamic ablation of cancer cells, demonstrating its dual role as an imaging and phototherapeutic agent.
Project description:Articulated structures of naphthalene-based donor (D)-acceptor (A) type dipolar dye and aggregation-induced emission luminogen (AIEgen) based on tetraphenylethylene (TPE) were synthesized, and their photophysical properties were analyzed for the first time. There are many fluorophore backbones, which have dipolar structure and AIEgen. However, there has been neither property analysis nor research that closely articulates DA and AIE through non-conjugation linker. We have therefore prepared two representative fluorophores; DA-AIE series (DA-AIE-M and DA-AIE-D), and characterized their UV/vis absorption and emission properties with quantum chemical calculations. In addition, we utilized the unique photophysical properties of DA-AIE-D for monitoring a trace of dimethyl sulfoxide (DMSO) in aqueous media, including real water samples.
Project description:Luminogens with aggregation-induced emission (AIE) characteristics are nowadays undergoing explosive development in the fields of imaging, process visualization, diagnosis and therapy. However, exploration of an AIE luminogen (AIEgen) system allowing for extremely wide color tunability remains challenging. In this contribution, the facile synthesis of triphenylamine (TPA)-thiophene building block-based AIEgens having tunable maximum emission wavelengths covering violet, blue, green, yellow, orange, red, deep red and NIR regions is reported. The obtained AIEgens can be utilized as extraordinary fluorescent probes for lipid droplet (LD)-specific cell imaging and cell fusion assessment, showing excellent image contrast to the cell background and high photostability, as well as satisfactory visualization outcomes. Interestingly, quantitative evaluation of the phototherapy effect demonstrates that one of these presented AIEgens, namely TTNIR, performs well as a photosensitizer for photodynamic ablation of cancer cells upon white light irradiation. This study thus provides useful insights into rational design of fluorescence systems for widely tuning emission colors with high brightness, and remarkably extends the applications of AIEgens.
Project description:High-fidelity tracking of specific enzyme activities is critical for the early diagnosis of diseases such as cancers. However, most of the available fluorescent probes are difficult to obtain <i>in situ</i> information because of tending to facile diffusion or inevitably suffering from aggregation-caused quenching (ACQ) effect. In this work, we developed an elaborated near-infrared (NIR) aggregation-induced emission (AIE)-active fluorescent probe, which is composed of a hydrophobic 2-(2-hydroxyphenyl) benzothiazole (HBT) moiety for extending into the NIR wavelength, and a hydrophilic ?-galactosidase (?-gal) triggered unit for improving miscibility and guaranteeing its non-emission in aqueous media. This probe is virtually activated by ?-gal, and then specific enzymatic turnover would liberate hydrophobic AIE luminogen (AIEgen) QM-HBT-OH. Simultaneously, brightness NIR fluorescent nanoaggregates are <i>in situ</i> generated as a result of the AIE-active process, making on-site the detection of endogenous ?-gal activity in living cells. By virtue of the NIR AIE-active performance of enzyme-catalyzed nanoaggregates, QM-HBT-?gal is capable of affording a localizable fluorescence signal and long-term tracking of endogenous ?-gal activity. All results demonstrate that the probe QM-HBT-?gal has potential to be a powerful molecular tool to evaluate the biological activity of ?-gal, attaining high-fidelity information in preclinical applications.
Project description:BACKGROUND:Efficient and highly controllable antibacterial effect, as well as good biocompatibility are required for antibacterial materials to overcome multi-drug resistance in bacteria. Herein, nano graphene oxide (NGO)-based near-infrared (NIR) photothermal antibacterial materials was schemed to complex with biocompatible bovine serum albumin (BSA) and aggregation-induced emission fluorogen (AIEgen) with daylight-stimulated ROS-producing property for dual-mode phototherapy in the treatment of antibiotic resistance bacteria. RESULTS:Upon co-irradiation of daylight and NIR laser, NGO-BSA-AIE nanoparticles (NPs) showed superiorly antibacterial effect (more than 99%) both against amoxicillin (AMO)-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by comparison with sing-model phototherapy. Meanwhile, the NGO-BSA-AIE NPs displayed prominent stability and excellently controllable biocompatibility. More importantly, under daylight irradiation, the AIEgen not only produced plentiful ROS for killing bacteria, but also presented fluorescence image for tracking bacteria. CONCLUSIONS:Hence, the designed system provided tempting strategy of employing light as impetus for tracking bacterial distribution and photothermal/photodynamic synergistic treatment of antibiotic resistance antibacterial.
Project description:A facile and efficient approach for design and synthesis of organic fluorescent nanogels has been developed by using a pre-synthesized polymeric precursor. This strategy is achieved by two key steps: (i) precise synthesis of core?shell star-shaped block copolymers with crosslinkable AIEgen-precursor (AIEgen: aggregation induced emission luminogen) as pending groups on the inner blocks; (ii) gelation of the inner blocks by coupling the AIEgen-precursor moieties to generate AIE-active spacers, and thus, fluorescent nanogel. By using this strategy, a series of star-shaped block copolymers with benzophenone groups pending on the inner blocks were synthesized by grafting from a hexafunctional initiator through atom transfer radical copolymerization (ATRP) of 4-benzoylphenyl methacrylate (BPMA) or 2-(4-benzoylphenoxy)ethyl methacrylate (BPOEMA) with methyl methacrylate (MMA) and tert-butyldimethylsilyl-protected 2-hydroxyethyl methacrylate (ProHEMA) followed by a sequential ATRP to grow PMMA or PProHEMA. The pendent benzophenone groups were coupled by McMurry reaction to generate tetraphenylethylene (TPE) groups which served as AIE-active spacers, affording a fluorescent nanogel. The nanogel showed strong emission not only at aggregated state but also in dilute solution due to the strongly restricted inter- and intramolecular movement of TPE moiety in the crosslinked polymeric network. The nanogel has been used as a fluorescent macromolecular additive to fabricate fluorescent film.
Project description:The rational design of robust fluorescent organic materials for long-term cell tracing is still challenging, and aggregation-caused quenching of emission is a big limitation of this strategy. Organic dyes with aggregation-induced emission (AIE) can effectively address this problem. Herein, AIEgen-containing nanoparticles, with different morphologies and emission, were prepared by assembling amphiphilic copolymers with an AIEgen. We compared the physical and chemical properties of rod-like and spherical nanoparticles, particularly investigating the effects of the shape on internalization and the imaging effect. The formulated nanoparticles exhibit advantageous features, such as a large Stokes shift, robust stability in physiological conditions, strong fluorescent emission, and photobleaching resistance. Interestingly, the rod-like nanoparticles were internalized more efficiently than their spherical counterparts, and their strong green fluorescence can still be clearly observed even after 15 days in vitro and in vivo. This work demonstrates the great potential of regulating the morphology of nanoparticles to obtain an ideal biological function.
Project description:Photosensitizers are generally treated as key components for photodynamic therapy. In contrast, we herein report an aggregation-induced emission luminogen (AIEgen)-based photosensitizer (TPE-Py-FFGYSA) that can serve as a non-toxic adjuvant to amplify the antitumor efficacy of paclitaxel, a well-known anticancer drug, with a synergistic effect of "0 + 1 > 1". Besides the adjuvant function, TPE-Py-FFGYSA can selectively light up EphA2 protein clusters overexpressed in cancer cells in a fluorescence turn-on mode, by taking advantage of the specific YSA peptide (YSAYPDSVPMMS)-EphA2 protein interaction. The simple incorporation of FFG as a self-assembly-aided unit between AIEgen (TPE-Py) and YSA significantly enhances the fluorescent signal output of TPE-Py when imaging EphA2 clusters in live cancer cells. Cytotoxicity and western blot studies reveal that the reactive oxygen species (ROS) generated by TPE-Py-FFGYSA upon exposure to light do not kill cancer cells, but instead provide an intracellular oxidative environment to help paclitaxel have much better efficacy. This study thus not only extends the application scope of photosensitizers, but also offers a unique theranostic system with the combination of diagnostic imaging and adjuvant antitumor therapy.
Project description:In the present work, we describe a facile and general method of fabricating fluorescent inorganic nanoparticles with diverse shapes for cell imaging application. The hematite (α-Fe₂O₃) nanoparticles (HNPs) with three different shapes (i.e., spindle shape, ellipsoidal shape and quasi-spherical shape) were first prepared as model systems in consideration of good biocompatibility and the controllable morphology of α-Fe₂O₃. Three fluorescent HNPs with different shapes were readily achieved via one-pot sol-gel reaction of AIE luminogen-functionalized siloxane (AIEgen-Si(OCH₃)₃) and TEOS in the presence of PVP-stabilized HNPs. Due to the fluorescence originating from the thin AIEgens-contained SiO₂ shell around the HNPs, their photoluminescent intensities can be tuned by changing the concentrations of TEOS and AIEgen-Si(OCH₃)₃ in feed prior to the sol-gel reaction. When the as-prepared fluorescent products were dispersed in water, they gave intense green light emission upon excitation at 360 nm with relatively high fluorescence quantum yield. Further, fluorescent HNPs exhibited low cytotoxicity and excellent photostability and, thus, were used as optical probes to preliminarily explore the effect of nanoparticle shapes on their cellular uptake behaviors. This work should open a facile way to prepare various fluorescent inorganic nanoparticles with specific morphology for various biological applications.
Project description:A ?-extended tetraphenylethylene derivative 1 was developed as a fluorescent "turn-on" and "naked-eye" color change probe for hydrazine detection. Probe 1 was composed of the representative AIE luminogen (AIEgen), tetraphenylethylene, and a dicyanovinyl group was adopted for hydrazine recognition. Upon exposure of hydrazine, probe 1 immediately gave a significant aggregation-induced emission around 575 nm and excellent photostability. A naked-eye color change was also observed from red to yellow. Moreover, probe 1 was simply coated with a glass-backed silica gel-coated thin-layer chromatography plate, showing rapid and on-site detection of hydrazine vapor.
Project description:Development of fluorescent probes for on-site sensing and long-term tracking of specific biomarkers is particularly desirable for the early detection of diseases. However, available small-molecule probes tend to facilely diffuse across the cell membrane or remain at the activation site but always suffer from the aggregation-caused quenching (ACQ) effect. Here we report an enzyme-activatable aggregation-induced emission (AIE) probe QM-?gal, which is composed of a hydrophilic ?-galactosidase (?-gal)-triggered galactose moiety and a hydrophobic AIE-active fluorophore QM-OH. The probe is virtually non-emissive in aqueous media, but when activated by ?-gal, specific enzymatic turnover would liberate hydrophobic AIE luminogen (AIEgen) QM-OH, and then highly fluorescent nanoaggregates are in situ generated as a result of the AIE process, allowing for on-site sensing of endogenous ?-gal activity in living cells. Notably, taking advantage of the improved intracellular retention of nanoaggregates, we further exemplify QM-?gal for long-term (?12 h) visualization of ?-gal-overexpressing ovarian cancer cells with high fidelity, which is essential for biomedicine and diagnostics. Thus, this enzyme-activatable AIE probe not only is a potent tool for elucidating the roles of ?-gal in biological systems, but also offers an enzyme-regulated liberation strategy to exploit multifunctional probes for preclinical applications.