RESUMO
Planar luminogens have encountered difficulties in overcoming intrinsic aggregation-caused emission quenching by intermolecular π-π stacking interactions. Although excited-state double-bond reorganization (ESDBR) can guide us on designing planar aggregation-induced emission (AIE) luminogens (AIEgens), its mechanism has yet been elucidated. Major challenges in the field include methods to efficiently restrict ESDBR and enhance AIE performance without using bulky substituents (e.g., tetraphenylethylene and triphenylamine). In this study, we rationally developed fluoro-substituent AIEgens with stronger intermolecular H-bonding interaction for restricted molecular motions and increased crystal density, leading to decreased nonradiative decay rate by one order of magnitude. The adjusted ESDBR properties also show a corresponding response to variation in viscosity. Furthermore, their aggregation-induced reactive oxygen species (ROS) generations have been discovered. The application of such planar AIEgen in treating multidrug-resistant bacteria has been demonstrated in a mouse model. The relationship between ROS generation and distinct E/Z-configurational stacking behaviors have been further understood, providing a design principle for synthesizing planar AIEgen-based photosensitizers.
Assuntos
Corantes Fluorescentes/química , Animais , Infecções Bacterianas/tratamento farmacológico , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Desenho de Fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Luminescência , Camundongos , Camundongos Endogâmicos BALB C , Imagem Óptica , Espécies Reativas de OxigênioRESUMO
A robust platform is developed to assemble sub-10â nm organic aggregation-induced emission (AIE) particles using four different AIE luminogens (AIEgens) with emissions from green to the second near-infrared window (NIR-II). They are called AIE quantum dots (QDs) to distinguish from typical AIE dots which are larger than 25â nm. Compared with AIE dots that are larger than 25â nm, AIE QDs allow more efficient cellular uptake and imaging without surface modification of any membrane-penetrating peptides or other targeting molecules. NIR-II AIEgens, which have nearly no background fluorescence from organisms, are used to demonstrate that AIE QDs can achieve high contrast at the tumor as small as 80â mm3 and evade the liver more efficiently than AIE dots. AIE QDs hold a good promise for sensitive and precise diagnosis of the latent solid tumor in clinical medicine with much lower off-targeting to the liver than AIE dots.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Corantes Fluorescentes/química , Fígado/metabolismo , Técnicas Analíticas Microfluídicas , Imagem Óptica , Pontos Quânticos/química , Animais , Células Cultivadas , Feminino , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/farmacocinética , Humanos , Hidrodinâmica , Fígado/química , Células MCF-7 , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Camundongos , Tamanho da Partícula , Pontos Quânticos/metabolismo , Propriedades de Superfície , Distribuição TecidualRESUMO
Pathogen infections and cancer are two major human health problems. Herein, we report the synthesis of an organic salt photosensitizer (PS), called 4TPA-BQ, by a one-step reaction. 4TPA-BQ presents aggregation-induced emission features. Owing to the aggregation-induced reactive oxygen species generated and a sufficiently small ΔEST , 4TPA-BQ shows a satisfactorily high 1 O2 generation efficiency of 97.8 %. Inâ vitro and inâ vivo experiments confirmed that 4TPA-BQ exhibited potent photodynamic antibacterial performance against ampicillin-resistant Escherichia coli with good biocompatibility in a short time (15â minutes). When the incubation duration persisted long enough (12â hours), cancer cells were ablated efficiently, leaving normal cells essentially unaffected. This is the first reported time-dependent fluorescence-guided photodynamic therapy in one individual PS, which achieves ordered and multiple targeting simply by varying the external conditions. 4TPA-BQ reveals new design principles for the implementation of efficient PSs in clinical applications.
Assuntos
Técnicas de Ablação , Terapia de Alvo Molecular , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Células A549 , Animais , Células COS , Chlorocebus aethiops , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , HumanosRESUMO
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.
Assuntos
Corantes Fluorescentes , Nanopartículas , Animais , Fluorescência , Camundongos , Imagem Óptica , Polietilenoglicóis , Polímeros , CoelhosRESUMO
Fluorescence probes with aggregation-induced emission (AIE) characteristics are of great importance in biomedical imaging with superior spatial and temporal resolution. However, the lack of toxicity studies and deep tissue imaging in nonhuman primates hinders their clinical translation. Here, we report the blood chemistry and histological analysis in nonhuman primates treated with AIE probes over tenfold of an intravenous dose of clinically used indocyanine green (ICG) during a study period of 36 days to demonstrate AIE probes are nontoxic. Furthermore, through bright and nontoxic AIE probes and fluorescence imaging in the second window (NIR-II, 1,000-1,700 nm), we achieve an unprecedented 1.5-centimeter-deep vascular imaging in nonhuman primates, breaking the current limitation of millimeter-deep NIR-II fluorescence imaging. Our important findings, i.e., nontoxic features of AIE probes and centimeter-deep NIR-II vascular imaging in nonhuman primates, may facilitate successful translation of AIE probes in clinical trials.