AIE-active theranostic system: selective staining and killing of cancer cells.
ABSTRACT: Cancer is the leading cause of death worldwide. With the advantages of low cost, high sensitivity and ease of accessibility, fluorescence imaging has been widely used for cancer detection in the scientific field. Aggregation-induced emission luminogens (AIEgens) are a class of synthesized fluorescent probes with high brightness and photostability in the aggregate state. Herein, a new positively-charged AIEgen, abbreviated as TPE-IQ-2O, is designed and characterized. TPE-IQ-2O not only can distinguish cancer cells from normal cells with high contrast with the aid of the difference in mitochondrial membrane potential as well as the quantity of mitochondria, but it also works as a promising photosensitizer to kill cancer cells through generation of reactive oxygen species upon white light irradiation, thus making it a promising AIE theranostic system.
Project description:Aggregation-induced emission (AIE) as a unique photophysical process has been intensively explored for their features in fields from optical sensing, bioimaging to optoelectronic devices. However, all AIE luminogens (AIEgens) hardly recover into the initial dispersed state after illuminating at the ultimate aggregated state, which limits AIEgens to achieve reversible sensing and reproducible devices. To real-time manipulate the emission of AIEgen, here we take the advantage of confined space in the quartz nanopore to achieve a nanopore-size-dependent restriction of AIEgens for reversible conversions of "on-to-off" and "off-to-on" emission. By electrochemically manipulating 26?fL AIEgen solution inside nanopore confinement, AIE illuminates while moves along nanopore from the constricted tip to inside cavity at a velocity of 1.4-2.2??m?s-1, and vice versa. We further apply this dynamic manipulation for a target delivery of AIEgen into single cells, which opens up new possibility to design powerful and practical AIE applications.
Project description:Research on aggregation-induced emission (AIE) has been a hot topic. Due to enthusiastic efforts by many researchers, hundreds of AIE luminogens (AIEgens) have been generated which were mainly based on archetypal silole, tetraphenylethene, distyrylanthracene, triphenylethene, and tetraphenyl-1,4-butadiene, etc. To enlarge the family of AIEgens and to enrich their functions, new AIEgens are in high demand. In this work, we report a new kind of AIEgen based on tetraphenylpyrazine (TPP), which could be readily prepared under mild reaction conditions. Furthermore, we show that the TPP derivatives possess a good thermal stability and their emission could be fine-tuned by varying the substituents on their phenyl rings. It is anticipated that TPP derivatives could serve as a new type of widely utilized AIEgen, based on their facile preparation, good thermo-, photo- and chemostabilities, and efficient emission.
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:Aggregation-induced emission (AIE) has become a hot research area and tremendous amounts of AIE-active luminogens (AIEgens) have been generated. To further promote the development of AIE, new AIEgens are highly desirable. Herein, new AIEgens based on tetraphenylpyrimidine (TPPM) are rationally designed according to the AIE mechanism of restriction of intramolecular motion, and facilely prepared under mild reaction conditions. The photophysical property of the generated TPPM, TPPM-4M and TPPM-4P are systematically investigated and the results show that they feature the aggregation-enhanced emission (AEE) characteristics. Theoretical study shows the high-frequency bending vibrations in the central pyrimidine ring of TPPM derivatives dominate the nonradiative decay channels. Thanks to the AEE feature, their aggregates can be used to detect explosives with super-amplification quenching effects, and the sensing ability is higher than typical AIE-active tetraphenylethene. It is anticipated that TPPM derivatives could serve as a new type of widely used AIEgen based on their facile preparation and good thermo-, photo- and chemostabilities.
Project description:Utilizing aggregation-induced emission luminogens (AIEgens) as ligands has proven to be an effective strategy for constructing metal-organic frameworks (MOFs) with intense luminescent properties. However, highly luminescent AIEgen-based MOFs with adjustable emission properties are rarely achieved because of the rigid conformation of AIEgens in the crystalline state. Here, a dual-node 3D silver chalcogenolate cluster MOF (1) is designed and synthesized, where the AIE ligand shows relatively flexible and rotatable conformations. The conformations of AIE ligands in 1 are switchable by the absorption/desorption of guest molecules. As a result, 1 exhibited not only intense but also guest molecule switched luminescent properties. More importantly, the switching rate is tunable by using different guest molecules. 1 provides a unique visualized prototype to understand the mechanism of guest-triggered aggregation-induced emission in MOFs.
Project description:Multiphoton microscopy is an exciting tool for biomedical research because it can be used to image single cells <i>in vivo</i> due to its greater penetration depth, lower phototoxicity and higher resolution when compared to confocal laser scanning microscopy. This helps researchers understand how certain cells change over time and evaluate the efficacy of different therapies. Herein, we report a new AIE luminogen (AIEgen), abbreviated as TPE-TETRAD, with a favorable absorption and efficient deep-red emission in the solid state. TPE-TETRAD possesses a high two-photon absorption cross-section (313 MG at 830 nm) and a rich array of non-linear optical properties including aggregation-induced three-photon luminescence. Biotinylated TPE-TETRAD nanoparticles are also fabricated and applied to stain mitochondria in live cancer cells with high specificity. The purpose of this study is to characterize a novel deep-red AIEgen and fabricate biotinylated nanoparticles for applications as (1) biocompatible and photostable AIE probes for specific mitochondria imaging and (2) multiphoton imaging probes suitable for two/three-photon fluorescence microscopy.
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:Luminogens with aggregation-induced emission (AIEgens) characteristics have been well developed and applied in various areas such as bio-imaging, theranostics, organic photoelectronics and chemo/bio sensors. However, most of the reported AIEgens suffer from the disadvantages of complex organic synthesis and high cost, as well as being environmentally unfriendly and hard to degrade, which have largely limited their real applications. In this work, we discovered berberine chloride, a natural isoquinoline alkaloid isolated from Chinese herbal plants, as an unconventional rotor-free AIEgen with bright solid-state emission and water-soluble characteristics. Single crystal structure analysis and optical property, viscosity, and host-guest interaction studies suggested that intramolecular vibration and twisted intramolecular charge transfer were responsible for the AIE phenomenon of berberine chloride. Moreover, berberine chloride was biocompatible and could specifically target lipid droplets in a fluorescence turn-on and wash-free manner, demonstrating the great potential of natural products as promising AIE probes.
Project description:Aggregation-induced emission (AIE) has become a hot topic for a variety of potential applications, but the understanding of its working mechanism is still under scrutiny. Herein, we proposed the use of the isotope effect (IE) to identify the AIE mechanism: under the restriction of an internal motion mechanism, the IE is pronouncedly different in excited-state decay rates when contrasting AIE luminogens (AIEgens) and non-AIEgens in theoretical calculations. For the complete deuteration of AIEgens, the IE of nonradiative decay rate in solution (<-10%) is much weaker than that (-65% to -95%) in aggregate, because the former stems from the overall results of competitive vibronic coupling and the severe mixing of low-frequency modes while the latter mainly comes from the vibronic coupling only. The experimental results confirm the isotopic "jump" behaviors in AIEgens well. However, non-AIEgens exhibit equivalent IEs (-40% to -90%) in both solution and solid phases. Further partial deuteration schemes for the 6-ring AIE analogues show positional dependence.
Project description:Aggregation-induced emission (AIE) can be generated due to the restriction of intramolecular motions. The controllable assembly of fluorogens with AIE properties (AIEgens) is able to provide a new opportunity for precise manipulation of fluorescent signal transduction. Here, a tetrapod DNA quadruplex (TP-G4) was designed as a molecular scaffold for assembly and precise modulation of light emission of an oligonucleotide-grafted fluorogen with aggregation-induced emission (Oligo-AIEgen). The Oligo-AIEgen was synthesized by attaching the AIEgen to the 3'-terminus of the oligonucleotide through a dibenzylcyclooctyne mediated coupling reaction. The AIEgen emitted no detectable fluorescence in the context of a double-stranded structure. When hybridized to the parallel-stranded TP-G4, several AIEgens were located in close proximity to generate fluorescence. The fluorescence intensity has been precisely regulated by manipulation of the spacer length between the core structure of the scaffold and AIEgen, as well as by altering the quartet number of the G-quadruplex. Similar control of fluorescence was also demonstrated using tetramolecular and bimolecular i-motif quadruplex structures as the scaffolds. These scaffolds provide a proof of concept on the manipulation of molecular interactions, which forms a universal molecular tool for the design of new biosensing strategies.