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.
Lacking rapid and reliable pathogen diagnostic platforms, inadequate or delayed antimicrobial therapy could be made, which greatly threatens human life and accelerates the emergence of ...antibiotic‐resistant pathogens. In this contribution, a series of simple and reliable sensor arrays based on tetraphenylethylene (TPE) derivatives are successfully developed for detection and discrimination of pathogens. Each sensor array consists of three TPE‐based aggregation‐induced emission luminogens (AIEgens) that bear cationic ammonium group and different hydrophobic substitutions, providing tunable logP (n‐octanol/water partition coefficient) values to enable the different multivalent interactions with pathogens. On the basis of the distinctive fluorescence response produced by the diverse interaction of AIEgens with pathogens, these sensor arrays can identify different kinds of pathogens, even normal and drug‐resistant bacteria, with nearly 100% accuracy. Furthermore, blends of pathogens can also be identified accurately. The sensor arrays exhibit rapid response (about 0.5 h), high‐throughput, and easy‐to‐operate without washing steps.
A series of simple and reliable sensor arrays based on aggregation‐induced emission (AIE)‐active tetraphenylethylene derivatives are successfully developed for fast and accurate pathogen identification. Based on the distinctive fluorescence response produced by the multivalent interaction of AIE luminogens with pathogens, these sensor arrays can identify different pathogens, even normal and drug‐resistant bacteria, with nearly 100% accuracy.
Personal protective equipment (PPE) is vital for the prevention and control of SARS-CoV-2. However, conventional PPEs lack virucidal capabilities and arbitrarily discarding used PPEs may cause a high ...risk for cross-contamination and environmental pollution. Recently reported photothermal or photodynamic-mediated self-sterilizing masks show bactericidal–virucidal abilities but have some inherent disadvantages, such as generating unbearable heat during the photothermal process or requiring additional ultraviolet light irradiation to inactivate pathogens, which limit their practical applications. Here, we report the fabrication of a series of fabrics (derived from various PPEs) with real-time self-antiviral capabilities, on the basis of a highly efficient aggregation-induced emission photosensitizer (namely, ASCP-TPA). ASCP-TPA possesses facile synthesis, excellent biocompatibility, and extremely high reactive oxygen species generation capacity, which significantly outperforms the traditional photosensitizers. Meanwhile, the ASCP-TPA-attached fabrics (ATaFs) show tremendous photodynamic inactivation effects against MHV-A59, a surrogate coronavirus of SARS-CoV-2. Upon ultralow-power white light irradiation (3.0 mW cm–2), >99.999% virions (5 log) on the ATaFs are eliminated within 10 min. Such ultralow-power requirement and rapid virus-killing ability enable ATaFs-based PPEs to provide real-time protection for the wearers under indoor light irradiation. ATaFs’ virucidal abilities are retained after 100 washings or continuous exposure to office light for 2 weeks, which offers the benefits of reusability and long-term usability. Furthermore, ATaFs show no toxicity to normal skin, even upon continuous high-power light illumination. This self-antiviral ATaFs-based strategy may also be applied to fight against other airborne pathogens and holds huge potential to alleviate global PPE supply shortages.
Improving photothermal conversion efficiency (PCE) is critical to facilitate therapeutic performance during photothermal therapy (PTT). However, current strategies of prompting PCE always involve ...complex synthesis or modification of photothermal agents, thereby significantly inhibiting the practical applications and fundamental understanding of photothermal conversion. A facile strategy is herein present for boosting PCE by transforming photothermal agents from aggregated state to dispersed state. Compared to aggregated state, the developed photothermal agents with semiconducting nature can rotate freely in dispersed state, which allows for an efficient nonradiative dissipation through twisted intramolecular charge transfer (TICT) effect, consequentially offering excellent photothermal performance. Noteworthy, the state transformation can be achieved by virtue of releasing photothermal molecules from nanoparticles on the basis of a pH‐responsive polymer nanocarrier, and the PCE is elevated from 43% to 60% upon changing the pH values from 7.4 to 5.0. Moreover, the nanoparticle disassembly and state transformation behaviors can also smoothly proceed in lysosome of cancer cells, demonstrating a distinct photothermal therapeutic performance for cancer ablation. It is hoped that this strategy of transforming state to boost PCE would be a new platform for practical applications of PTT technique.
A facile strategy of improving photothermal conversion efficiency (PCE) is presented through transforming photothermal agents from aggregated to dispersed state, where the intramolecular motions are completely liberated, allowing for supra‐efficient heat generation. This state transformation can be achieved by virtue of a releasing process from nanoparticles in cancer cells, demonstrating a distinct photothermal therapeutic performance for cancer ablation.
The efficient utilization of energy dissipating from non‐radiative excited‐state decay of fluorophores was only rarely reported. Herein, we demonstrate how to boost the energy generation of ...non‐radiative decay and use it for cancer theranostics. A novel compound (TFM) was synthesized which possesses a rotor‐like twisted structure, strong absorption in the far red/near‐infrared region, and it shows aggregation‐induced emission (AIE). Molecular dynamics simulations reveal that the TFM aggregate is in an amorphous form consisting of disordered molecules in a loose packing state, which allows efficient intramolecular motions, and consequently elevates energy dissipation from the pathway of thermal deactivation. These intrinsic features enable TFM nanoparticles (NPs) to display a high photothermal conversion efficiency (51.2 %), an excellent photoacoustic (PA) effect, and effective reactive oxygen species (ROS) generation. In vivo evaluation shows that the TFM NPs are excellent candidates for PA imaging‐guided phototherapy.
No radiation, no problem! A novel AIEgen was synthesized and confirmed to be an excellent platform for elevating energy dissipation from nonradiative decay. This AIEgen has a high photothermal conversion efficiency (51.2 %), an excellent photoacoustic effect and effective reactive oxygen species generation, making it powerful in multi‐modality theranostics for cancer treatment.
Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive ...PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation‐induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far‐red/near‐infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three‐pronged PDT.
Power of three: A synergistic enhanced photodynamic therapy (PDT) strategy was developed that concurrently acts on multiple subcellular organelles. At the same photosensitizer concentration, combined PDT treatment with three aggregation‐induced emission luminogens (AIEgens) exhibits superior therapeutic effect than that of single AIEgens.
Fluorescence‐imaging‐guided photodynamic therapy has emerged as a promising protocol for cancer theranostics. However, facile preparation of such a theranostic material for simultaneously achieving ...bright emission with long wavelength, high‐performance reactive oxygen species (ROS) generation, and good targeting‐specificity of cancer cells, is highly desirable but remains challenging. In this study, a novel type of far‐red/near‐infrared‐emissive fluorescent molecules with aggregation‐induced emission (AIE) characteristics is synthesized through a few steps reaction. These AIE luminogens (AIEgens) possess simple structures, excellent photostabilities, large Stokes shifts, bright emission, and good biocompatibilities. Meanwhile, their ROS generation is extremely efficient with up to 90.7% of ROS quantum yield, which is far superior to that of some popularly used photosensitizers. Importantly, these AIEgens are able to selectively target and ablate cancer cells over normal cells without the aid of any extra targeting ligands. Rather than using laser light, one of the presented AIEgens (MeTTPy) shows a remarkable tumor‐targeting photodynamic therapeutic effect by using an ultralow‐power lamp light (18 mW cm−2). This study thus not only extends the applications scope of AIEgens, but also offers useful insights into designing a new generation of cancer theranostics.
Highly efficient photosensitizers with far‐red/near‐infrared aggregation‐induced emission are facilely synthesized and used for in vitro and in vivo cancer theranostics. These materials are able to selectively target and ablate cancer cells over normal cells without the aid of any extra targeting ligands, and show a remarkable tumor‐targeting photodynamic therapeutic effect by using an ultralow‐power lamp light (18 mW cm−2).
Summary Background Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. It is a multisystem disease caused by Borrelia burgdorferi sensu lato genospecies and ...characterised by tissue localisation and low spirochaetaemia. In this study we aimed to describe a novel Borrelia species causing Lyme borreliosis in the USA. Methods At the Mayo clinic, from 2003 to 2014, we tested routine clinical diagnostic specimens from patients in the USA with PCR targeting the oppA1 gene of B burgdorferi sensu lato. We identified positive specimens with an atypical PCR result (melting temperature outside of the expected range) by sequencing, microscopy, or culture. We collected Ixodes scapularis ticks from regions of suspected patient tick exposure and tested them by oppA1 PCR. Findings 100 545 specimens were submitted by physicians for routine PCR from Jan 1, 2003 to Sept 30, 2014. From these samples, six clinical specimens (five blood, one synovial fluid) yielded an atypical oppA1 PCR product, but no atypical results were detected before 2012. Five of the six patients with atypical PCR results had presented with fever, four had diffuse or focal rash, three had symptoms suggestive of neurological inclusion, and two were admitted to hospital. The sixth patient presented with knee pain and swelling. Motile spirochaetes were seen in blood samples from one patient and cultured from blood samples from two patients. Among the five blood specimens, the median oppA1 copy number was 180 times higher than that in 13 specimens that tested positive for B burgdorferi sensu stricto during the same time period. Multigene sequencing identified the spirochaete as a novel B burgdorferi sensu lato genospecies. This same genospecies was detected in ticks collected at a probable patient exposure site. Interpretation We describe a new pathogenic Borrelia burgdorferi sensu lato genospecies (candidatus Borrelia mayonii ) in the upper midwestern USA, which causes Lyme borreliosis with unusually high spirochaetaemia. Clinicians should be aware of this new B burgdorferi sensu lato genospecies, its distinct clinical features, and the usefulness of oppA1 PCR for diagnosis. Funding US Centers for Disease Control and Prevention Epidemiology and Laboratory Capacity for Infectious Diseases (ELC) Cooperative Agreement and Mayo Clinic Small Grant programme.
With the increase of bacterial infections in clinical practice, it becomes a public health problem which has aroused worldwide attention. Fluorescence imaging-guided photodynamic antibiosis has ...recently emerged as a promising protocol to solve this problem. However, developing a super powerful fluorescent material allowing facile preparation, long emission wavelength, rapid bacterial discrimination, washing-free staining, and high photodynamic antibacterial efficiency in a single entity, is highly desirable but remains challenging. In this study, we utilize for the first time a water-soluble near-infrared (NIR) emissive luminogen with aggregation-induced emission (AIE) characteristics, namely TTVP, for simultaneous dual applications of Gram-positive bacteria discrimination and photodynamic antibiosis. TTVP is able to selectively target Gram-positive bacteria over Gram-negative bacteria through a washing-free procedure after only 3 s incubation period, which is at least 100-fold shorter than those of previously reported protocols, implying ultrafast bacterial discrimination features. Meanwhile, TTVP exhibits extremely high reactive oxygen species generation efficiency, which is far superior to that of most popularly used photosensitizers, representing one of the best candidates for photodynamic antibiosis. In vitro and in vivo results demonstrate that TTVP provides extraordinary performance on photodynamic antibacterial therapy. This study thus offers a blueprint for the next generation of antibacterial materials.
Red/near‐infrared (NIR) fluorescent molecules with aggregation‐induced emission (AIE) characteristics are of great interest in bioimaging and therapeutic applications. However, their complicated ...synthetic approaches remain the major barrier to implementing these applications. Herein, a one‐pot synthetic strategy to prepare a series of red/NIR‐emissive AIE luminogens (AIEgens) by fine‐tuning their molecular structures and substituents is reported. The obtained AIEgens possess simple structures, good solubilities, large Stokes shifts, and bright emissions, which enable their applications toward in vitro and in vivo imaging without any pre‐encapsulation or ‐modification steps. Excellent targeting specificities to lipid droplets (LDs), remarkable photostabilities, high brightness, and low working concentrations in cell imaging application make them remarkably impressive and superior to commercially available LD‐specific dyes. Interestingly, these AIEgens can efficiently generate reactive oxygen species upon visible light irradiation, endowing their effective application for photodynamic ablation of cancer cells. This study, thus, not only demonstrates a facile synthesis of red/NIR AIEgens for dual applications in simultaneous imaging and therapy, but also offers an ideal architecture for the construction of AIEgens with long emission wavelengths.
A one‐pot synthetic strategy is described for preparing red‐ and near‐infrared‐emissive aggregation‐induced emission (AIE) luminogens (AIEgens) with simple structures, large Stokes shifts, and bright emissions. These AIEgens can be utilized as lipid droplet‐specific bioprobes in cell imaging and in vivo zebrafish imaging with high photostabilities and brightness. They are also effective in photodynamic cancer cell ablation upon visible light irradiation.