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Pathogenic infectious diseases have persistently posed significant threats to public health. Phototheranostics, which combines the functions of diagnostic imaging and therapy, presents an extremely promising solution to block the spread of pathogens as well as the outbreak of epidemics owing to its merits of a wide-spectrum of activity, high controllability, non-invasiveness, and difficult to acquire resistance. Among multifarious phototheranostic agents, second near-infrared (NIR-II, 1000-1700 nm) aggregation-induced emission luminogens (AIEgens) are notable by virtue of their deep penetration depth, excellent biocompatibility, balanced radiative and nonradiative decay and aggregation-enhanced theranostic performance, making them an ideal option for combating pathogens. This minireview provides a systematical summary of the latest advancements in NIR-II AIEgens with emphasis on the molecular design and nanoplatform formulation to fulfill high-efficiency in treating bacterial and viral pathogens, classified by disease models. Then, the current challenges, potential opportunities, and future research directions are presented to facilitate the further progress of this emerging field.
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This minireview provides an overview of the recent advancements in the development of biomimetic Aggregation-Induced Emission (AIE) nanoparticles and their applications in disease diagnosis, phototherapy, and photoimmunotherapy. AIE nanoparticles can be engineered to enable efficient image-guided photodynamic and photothermal therapies, however, challenges related to immune defense and target specificity persist. To overcome these, coating biomimetic materials on the surface of AIE nanoparticles, which mimic the features and functions of native cells, have emerged as a promising solution. This minireview will highlight the synthesis strategies and discuss the biomedical application of biomimetic AIE nanoparticles.
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Materiales Biomiméticos , Nanopartículas , Fototerapia , Materiales Biomiméticos/química , Materiales Biomiméticos/uso terapéutico , Humanos , Nanopartículas/química , Nanopartículas/uso terapéutico , AnimalesRESUMEN
Bacterial photodynamic inactivation based on the combined actions of photosensitizers, light, and oxygen presents a promising alternative for eliminating bacteria compared to conventional water disinfection methods. However, a significant challenge in this approach is the inability to retrieve photosensitizers after phototreatment, posing potential adverse environmental impacts. Additionally, conventional photosensitizers often exhibit limited photostability and photodynamic efficiency. This study addresses these challenges by employing an aggregation-induced emission (AIE) photosensitizer, iron oxide magnetic nanoparticles (Fe3O4 MNPs), and Pluronic F127 to fabricate AIE magnetic nanoparticles (AIE MNPs). AIE MNPs not only exhibit fluorescence imaging capabilities and superior photosensitizing ability but also demonstrate broad-spectrum bactericidal activities against both Gram-positive and Gram-negative bacteria. The controlled release of TPA-Py-PhMe and magnetic characteristics of the AIE MNPs facilitate reuse and recycling for multiple cycles of bacterial inactivation in water. Our findings contribute valuable insights into developing environmentally friendly disinfectants, emphasizing the full potential of AIE photosensitizers in photodynamic inactivation beyond biomedical applications.
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Nanopartículas de Magnetita , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Antibacterianos , Bacterias Gramnegativas , Bacterias GrampositivasRESUMEN
The aggregation-induced emission photosensitizer (AIE PS) has stood out as an alternative and competent candidate in bacterial theranostics, particularly with the use of cationic AIE PS in bacterial discrimination and elimination. Most reported work emphasizes the role of electrostatic interaction between cationic AIE PS and negatively charged bacterial surfaces, enabling broad applications from bacterial discrimination to bacterial killing. However, the underlying targeting mechanism and the design rationale of the cationic AIE PS for effective bacterial labeling remain poorly investigated. In this Article, we designed and synthesized a series of cationic amphiphilic AIE PSs with different calculated log P values. Then, we systemically studied the relationship between the hydrophobicity variation of AIE PS and bacterial targeting outcomes, the dose of AIE PS needed to label various species of bacteria, and their photodynamic antibacterial efficiency. The findings in this work provide a better understanding of the unclear AIE PS-bacterial interaction mechanism and some insights into the structural design strategies of cationic amphiphilic AIE PS for better development in bacterial theranostics.
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Antibacterianos , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/farmacología , Antibacterianos/farmacología , Bacterias , Cationes , Electricidad EstáticaRESUMEN
Although photodynamic therapy (PDT) for thorough cancer treatment is hindered by the limited generation of reactive oxygen species (ROS) with short lifetime from photosensitizers, PDT-induced antitumor immune response remedies the defects. Previous studies show that inducing immunogenic cell deaths is an attractive approach to activate antitumor immunity, which confers a robust adjuvanticity to dying cancer cells. In this work, amphiphilic luminogens with aggregation-induced emission characteristics (AIEgens) are rationally designed and synthesized. By modulating the hydrophobic π-bridge and zwitterionic functional groups, these AIEgens exhibit tunable organelle specificity to lysosome, endoplasmic reticulum, and plasma membrane and enhance ROS generation ability. Notably, the membrane-targeting AIEgen namely TPS-2 induces cell death and membrane rupture via PDT to facilitate the release of antigens and activation of immune cells. Furthermore, the size-controlled TPS-2 nanoaggregates are found to serve as an adjuvant, promoting antigen accumulation and delivery to sufficiently boost the in vivo antitumor immunity by only one dose injection in a prophylactic tumor vaccination model. This work thus provides new insights into optimizing AIE photosensitizers via a hydrophobicity-hydrophilicity balance strategy for evoking an antitumor immunity and directly suppressing the distanced tumor. A single small-molecular system for PDT-stimulated antitumor immunity is envisioned.
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Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/tratamiento farmacológico , Orgánulos/metabolismoRESUMEN
Obesity is a surging public health risk and is often associated with fatal diseases, including diabetes, stroke, and myocardial infarction. Common methods for obesity treatment include diet control, weight-loss medicine, and bariatric surgery, but these methods are often ineffective or unsafe. Herein, we introduce a minimally invasive and effective approach to reduce excessive fat accumulation by utilizing red/near-infrared emissive and lipid droplet targeting aggregation-induced emissive luminogens (AIEgens), namely, TTMN and MeTTMN, for specific targeting and photoinduced peroxidation of large lipid droplets in adipocytes. The reported AIEgens can trace and monitor the formation process of adipocytes from pre-adipocytes with a high signal-to-noise ratio. In addition, the presented AIEgens act as Type I photosensitizer that generates highly reactive hydroxyl radicals and superoxides under white light to eliminate mature adipocytes through the chain reactions of lipid peroxidation, even under low oxygen supply. We also demonstrate the use of AIEgens for in vivo photodynamic therapy (PDT) for subcutaneous fat reduction treatment. This work demonstrates the use of AIEgen as a dual imaging and Type I photosensitizer for photodynamic therapeutics to induce adipocyte apoptosis, involving a simple fabrication and treatment process. The suggested in vivo photodynamic obesity treatment processes have negligible toxicity toward nontargeted normal tissues, providing an alternative approach for effective and relatively safer obesity treatment in the future.
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Fotoquimioterapia , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Peroxidación de Lípido , Fotoquimioterapia/métodos , Luz , Diagnóstico por ImagenRESUMEN
Owing to high sensitivity, selectivity, and non-invasiveness, fluorescence has been widely applied in the biomedical and sensing fields. Among the pool of fluorescent probes, luminogens with aggregation-induced emission (AIE) characteristic exhibit unique strengths in biological applications. However, most reported AIE luminogens (AIEgens) require complicated synthetic procedures, which raise the costs and biocompatibility concerns, especially in biomedical imaging and therapy. In contrast, bioproduct-inspired AIEgens (BioAIEgens) can compensate for the weakness of synthetic AIEgens in terms of their high biocompatibility, low costs, and easy preparation. This review highlights the latest development of BioAIEgens discovered from natural herbs, as well as their potential biomedical and sensing applications. As nature is full of potential resources, studying AIEgens from natural herbs can facilitate the strength of AIE properties in diverse applications and offer more inspiration to the future BioAIEgen structural design and development.
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Colorantes Fluorescentes , Fluorescencia , Colorantes Fluorescentes/químicaRESUMEN
Peroxynitrite (ONOO-) is a potent reactive nitrogen species that plays a role as a critical mediator in liver injury elicited by drugs such as acetaminophen (APAP). At a therapeutic dosage, most APAP is metabolized by liver cells and then excreted in the urine. However, excessive APAP intake can cause an acute production of ONOO-, which induces mitochondrial oxidative stress and necrosis of the liver cells. Therefore, the ONOO- levels in hepatocytes have been considered as an early sign of hepatotoxicity associated with drug overdosage. Herein, a ratiometric theranostic system based on aggregation-induced emission luminogens (AIEgens) for the visualization of ONOO- and reduction of drug-induced hepatotoxicity is developed. The AIEgen ATV-PPB shows a ratiometric fluorescence response from red to green upon cleavage of arylboronic ester moieties by ONOO- with high sensitivity and selectivity. Meanwhile, experiments reveal that ATV-PPB not only acts as a fluorescent probe for ONOO- but also as an intracellular ONOO- scavenger to reduce the hepatotoxicity under overdose APAP treatment.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Preparaciones Farmacéuticas , Acetaminofén/toxicidad , Animales , Hígado , Ratones , Ratones Endogámicos C57BL , Ácido Peroxinitroso , Medicina de PrecisiónRESUMEN
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.
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Nanomedicina TeranósticaRESUMEN
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.
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COVID-19 , Equipo de Protección Personal , Humanos , Fármacos Fotosensibilizantes/farmacología , SARS-CoV-2 , Antivirales , COVID-19/prevención & controlRESUMEN
Although phagocytosis serves as the front line to attack invading pathogens, its low bacterial encounter and killing rates leads to an ineffective bactericidal output. In view of this, developing multifunctional theranostic probe to effectively discriminate and ablate intracellular bacteria is highly desirable. However, the shielding effect of the host macrophages put the detection and elimination of macrophage-engulfed bacteria into a challenging task. Herein, we utilize a luminogen with aggregation-induced emission (AIE) characteristics, namely TTVP, as a simple and effective probe for simultaneous tracing and photodynamic killing of intracellular Gram-positive bacteria. With the help of the AIE property, excellent water solubility, near-infrared (NIR) emission and strong reactive oxygen species (ROS) generating ability, TTVP performed ideally to be a targeting agent to intracellular Gram-positive bacteria with high signal contrast, as well as to be a photosensitizer to effectively ablate intracellular bacteria without attacking host macrophages. This work thus provides insights for the next generation antibiosis theranostic application for potential clinical trials.
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Bacterias Grampositivas , Fotoquimioterapia , Antibacterianos/farmacología , Macrófagos , Fármacos Fotosensibilizantes , Especies Reactivas de OxígenoRESUMEN
Modifying different functional moieties into one platform is a conventional strategy for constructing theranostic systems. However, this strategy usually suffers from the unsatisfied efficiency of each individual function. Herein, a programmed self-assembly strategy is presented to fabricate theranostic nanoparticles, which significantly exhibit a dual-modality imaging function involving fluorescence imaging and magnetic resource imaging (MRI), and an efficient targeted therapy to cancer cells. Fluorescent vesicles are first self-assembled by aggregation-induced emission (AIE)-active molecules. Gd3+, serving as an MRI agent, is subsequently bound to the vesicles to provide highly positive charges, which have been realized to be anticancer active. Thereafter, transferrin (Tf) protein is introduced onto the surface of Gd3+ coordinated vesicles, shielding the positive charges and making the nanoparticles nontoxic to cells. With the assistance of Tf protein, the constructed nanoparticles are specifically targeted to cancer cells. Moreover, Tf proteins further peel off from nanoparticles in lysosomes due to their charge reversion, resulting in highly positive charges and heavy toxicity of nanoparticles to kill cancer cells. In the nanoparticles, each of the functional components acts as double-sided adhesive tape to glue the next layer, so that the abilities of functional components are not compromised. This strategy holds great potential for theranostic nanomedicine.
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Nanopartículas/química , Neoplasias/diagnóstico por imagen , Nanomedicina Teranóstica/métodos , Línea Celular Tumoral , Humanos , Imagen por Resonancia Magnética , Transferrina/químicaRESUMEN
Fully understanding the complicated interplays among various chemical species and organelles is greatly important to unravel the mystery of life. However, fluorescent probes capable of visualizing multiple targets discriminatively are severely deficient, which extremely limit the investigation on intracellular interplays among various species. Towards this end and in consideration of the unique advantages of aggregation-induced emission luminogens (AIEgens), here we rationally designed and presented a single AIEgen, named TVQE, bearing lipophilic, cationic and hydrolyzable moieties, and this AIEgen was capable of illuminating mitochondria and lipid droplets with red and blue emission, respectively. In addition, TVQE was successfully used for evaluating cell viability due to its distinct two-color emission changes tuned by esterase-mediated hydrolysis. Of particular importance is that TVQE can selectively differentiate live, early apoptotic, late apoptotic, and dead cells by confocal microscopy and quantify cell viability statistically by flow cytometry.
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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.
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Rayos Infrarrojos , Sustancias Luminiscentes/química , Fotoquimioterapia/métodos , Células HeLa , Humanos , Orgánulos/efectos de los fármacos , Orgánulos/efectos de la radiación , Fármacos Fotosensibilizantes/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates the cellular response to hypoxia. The upregulation of HIF-1 expression in hypoxic cells can induce the accumulation of lipid droplets (LDs), and the LD levels can in turn reflect the expression level of HIF-1. Herein, we report a LD-specific luminogen with aggregation-induced emission characteristics (AIEgen), and have explored its potential applications in the evaluation of the inhibitory efficacy of HIF-1 targeting drugs. Compared to Nile red, this AIEgen shows a larger Stokes shift, better photostability, a more sensitive response to changes in dye concentration and a broader quantitative range. We found that the AIEgen can be used for semi-quantifying LD levels in cancer cells under hypoxic conditions, and for evaluating the inhibitory efficacy of HIF-1 targeting drugs. This work provides a simple and cost-effective strategy for screening HIF-1-targeted drugs, which may also be an alternative for evaluating the drug efficacy of other LD-related diseases.
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Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Gotas Lipídicas/química , Imagen Óptica , Piridinas/farmacología , Células HeLa , Humanos , Factor 1 Inducible por Hipoxia/metabolismo , Gotas Lipídicas/metabolismo , Estructura Molecular , Tamaño de la Partícula , Piridinas/química , Propiedades de SuperficieRESUMEN
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 3â¯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.
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Antibacterianos , Fotoquimioterapia , Fármacos Fotosensibilizantes , Antibacterianos/farmacología , Bacterias Gramnegativas , Bacterias GrampositivasRESUMEN
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.
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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. Inâ vivo evaluation shows that the TFM NPs are excellent candidates for PA imaging-guided phototherapy.
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Terapia Combinada/métodos , Nanopartículas/química , Nanomedicina Teranóstica/métodos , HumanosRESUMEN
Facile, efficient, and mass production of aggregation-induced emission (AIE) luminogens (AIEgens) with excited-state intramolecular proton transfer (ESIPT) characteristics was achieved by a one-step condensation reaction of 2-(hydrazonomethyl)phenol with benzaldehydes. The function of as-prepared AIEgens could be tuned easily by varying the functional group being carried on the phenyl ring of benzaldehyde just like a Swiss knife handle. The suitable distance and angle of the intramolecular hydrogen bond in these AIEgens endowed them with ESIPT properties, intense solid-state luminescence, and large Stokes shifts (155-169 nm). These AIEgens could not only serve as biological probes showing specific targeting to lipid droplets, endoplasmic reticulum, and lysosomes, respectively, but also generate reactive oxygen species upon visible light irradiation to make them promise for photodynamic therapy.
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Benzaldehídos/química , Colorantes Fluorescentes/química , Imagen Óptica , Orgánulos/química , Fenoles/química , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Luz , Estructura Molecular , Protones , Especies Reactivas de Oxígeno/análisis , Relación Estructura-ActividadRESUMEN
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.