RESUMEN
Mitochondria are essential for a diverse array of biological functions. There is increasing research focus on developing efficient tools for mitochondria-targeted detection and treatment. BODIPY dyes, known for their structural versatility and excellent spectroscopic properties, are being actively explored in this context. Numerous studies have focused on developing innovative BODIPYs that utilize optical signals for imaging mitochondria. This review presents a comprehensive overview of the progress made in this field, aiming to investigate mitochondria-related biological events. It covers key factors such as design strategies, spectroscopic properties, and cytotoxicity, as well as mechanism to facilitate their future application in organelle imaging and targeted therapy. This work is anticipated to provide valuable insights for guiding future development and facilitating further investigation into mitochondria-related biological sensing and phototherapy.
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Compuestos de Boro , Colorantes Fluorescentes , Mitocondrias , Fotoquimioterapia , Compuestos de Boro/química , Compuestos de Boro/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Humanos , Colorantes Fluorescentes/química , Animales , Imagen Óptica , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacologíaRESUMEN
BACKGROUND AND AIMS: HCC is closely associated with inflammation and immune modulation, and combined chemotherapy with other strategies is under extensive investigation to achieve better efficacy. HCC is accompanied by zinc (Zn) deficiency. This study aims to understand how Zn could affect macrophage function and its application for HCC therapy. APPROACH AND RESULTS: Zn 2+ and the Zn transporter 1 (ZNT1, solute carrier family 30 member 1) were markedly reduced in intrahepatic macrophages from patients with HCC and from mouse liver tumors. Lower ZNT1 expression was associated with higher IL-6 production and shorter survival time in patients with HCC. Critically, ZNT1 regulated endosomal Zn 2+ levels for endocytosis of toll-like receptor 4 and programmed cell death ligand 1, thereby decreasing macrophage-induced inflammation and immunosuppression to protect from liver tumors. Myeloid-specific deletion of ZNT1 in mice increased chronic inflammation, liver fibrosis, tumor numbers, and size. Notably, Zn supplementation could reduce inflammation and surface programmed cell death ligand 1 expression in macrophages with the increased CD8 + T cell cytotoxicity, which synergized the antitumor efficacy of Sorafenib/Lenvatinib. CONCLUSIONS: Our study proposes a new concept that ZNT1 and Zn regulate endosome endocytosis to maintain surface receptors, and Zn supplements might be synergized with chemotherapy to treat inflammation-associated tumors, especially those containing programmed cell death ligand 1 + myeloid cells.
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Some important biological species and microenvironments maintain a complex and delicate dynamic balance in life systems, participating in the regulation of various physiological processes and playing indispensable roles in maintaining the healthy development of living bodies. Disruption of their homeostasis in living organisms can cause various diseases and even death. Therefore, real time monitoring of these biological species and microenvironments during different physiological and pathological processes is of great significance. Fluorescent-probe-based techniques have been recognized as one of the most powerful tools for real time imaging in biological samples. In this Account, we introduce the representative works from our group in the field of fluorescent probes for biological imaging capable of detecting metal ions, small bioactive molecules, and the microenvironment. The design strategies of small molecule fluorescent probes and their applications in biological imaging will be discussed. By regulating the design strategy and mechanism (e.g., ICT, PeT, and FRET) of the electronic and spectral characteristics of the fluorescent platforms, these chemical probes show high selectivity and diverse functions, which can be used for imaging of various physiological and pathological processes. Through the exploration of the rational response mechanism and design strategy, combined with a variety of imaging techniques, such as super-resolution imaging, photoacoustic (PA) imaging, etc., we have realized multimode imaging of the important biological analytes from the subcellular level to the in vivo level, which provides powerful means to study the physiological and pathological functions of these species and microenvironments. This Account aims to offer insights and inspiration for the development of novel fluorescent probes for biological imaging, which could provide powerful tools for the study of chemical biology. Overall, we represent a series of turn-on/turn-off/ratiometric fluorescent/PA probes to visually and dynamically trace biological species and microenvironments in cells and even in vivo that seek higher resolution and depth molecular imaging to improve diagnostic methods and clarify new discoveries related to chemical biology. Our future efforts will be devoted to developing multiorganelle targeted fluorescent probes to study the mechanism of subcellular organelle interaction and employing various dual-mode probes of NIR II and PA imaging to investigate the development of related diseases and treat the related diseases at subcellular and in vivo levels.
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Colorantes Fluorescentes , Orgánulos , Colorantes Fluorescentes/química , Metales , Imagen Molecular/métodosRESUMEN
As a new form of regulated cell death, ferroptosis is closely related to various diseases. Tracing ferroptosis related biological behavior is helpful to better understand this process and its related biology. Considering that ferroptosis is featured with remarkable lipid peroxidation which can easily change the membranes' compositions and structures, it is potential to detect intracellular environmental changes for direct assessment of ferroptosis. In view of the close relationship between endoplasmic reticulum (ER) and ferroptosis, we designed an ER-targeted and polarity-sensitive fluorescent probe SBD-CH, which has superior photostability and can respond to polarity with high selectivity without the affection of viscosity. SBD-CH can monitor the trend of ER polarity during ferroptosis by confocal laser scanning microscopy (CLSM), and analyze the distribution of polarity in ferroptosis by fluorescence lifetime imaging microscopy (FLIM). During Erastin induced ferroptosis, the polarity of ER in HT-1080 cells increased and the polarity distribution in ER was more dispersed. Our work provides an effective strategy for evaluating the process of ferroptosis by monitoring the changes of ER polarity.
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Retículo Endoplásmico , Ferroptosis , Colorantes Fluorescentes , Microscopía Confocal , Retículo Endoplásmico/metabolismo , Humanos , Colorantes Fluorescentes/química , Microscopía Confocal/métodos , Línea Celular Tumoral , Microscopía Fluorescente/métodos , Imagen Óptica , Peroxidación de Lípido , PiperazinasRESUMEN
Copper dysmetabolism is associated with various neurodegenerative disorders, making high-spatiotemporal-resolution imaging of Cu2+ in the brain essential for understanding the underlying pathophysiological processes. Nevertheless, the current probes encounter obstacles in crossing the blood-brain barrier (BBB) and providing high-spatial-resolution in deep tissues. Herein, we present a photoacoustic probe capable of imaging Cu2+ dynamics in the mouse brain with high-spatiotemporal-resolution. The probe demonstrates selective ratiometric and reversible responses to Cu2+ , while also efficiently crossing the BBB. Using the probe as the imaging agent, we successfully visualized Cu2+ in the brain of Parkinson's disease (PD) model mouse with a remarkable micron-level resolution. The imaging results revealed a significant increase in Cu2+ levels in the cerebral cortex as PD progresses, highlighting the close association between Cu2+ alternations in the region and the disease. We also demonstrated that the probe can be used to monitor changes in Cu2+ distribution in the PD model mouse brain during L-dopa intervention. Mechanism studies suggest that the copper dyshomeostasis in the PD mouse brain was dominated by the expression levels of divalent metal transporter 1. The application of our probe in imaging Cu2+ dynamics in the mouse brain offers valuable insights into the copper-related molecular mechanisms underlying neurodegenerative diseases.
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Cobre , Enfermedades Neurodegenerativas , Animales , Ratones , Cobre/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Barrera Hematoencefálica/metabolismo , Espectrometría de Fluorescencia , Diagnóstico por Imagen , Enfermedades Neurodegenerativas/metabolismo , Colorantes Fluorescentes/metabolismoRESUMEN
Nitric oxide (NO) exhibits both pro- and anti-tumor effects. Therefore, real-time in vivo imaging and quantification of tumor NO dynamics are essential for understanding the conflicting roles of NO played in pathophysiology. The current molecular probes, however, cannot provide high-resolution imaging in deep tissues, making them unsuitable for these purposes. Herein, we designed a photoacoustic probe with an absorption maximum beyond 1000â nm for high spatial quantitative imaging of in vivo tumor NO dynamics. The probe exhibits remarkable sensitivity, selective ratiometric response behavior, and good tumor-targeting abilities, facilitating ratiometric imaging of tumor NO throughout tumor progression in a micron-resolution level. Using the probe as the imaging agent, we successfully quantified NO dynamics in tumor, liver and kidney. We have pinpointed an essential concentration threshold of around 80â nmol/cm3 for NO, which plays a crucial role in the "double-edged-sword" function of NO in tumors. Furthermore, we revealed a reciprocal relationship between the NO concentration in tumors and that in the liver, providing initial insights into the possible NO-mediated communication between tumor and the liver. We believe that the probe will help resolve conflicting aspects of NO biology and guide the design of imaging agents for tumor diagnosis and anti-cancer drug screening.
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Óxido Nítrico , Técnicas Fotoacústicas , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Técnicas Fotoacústicas/métodos , Animales , Ratones , Humanos , Neoplasias/diagnóstico por imagen , Rayos Infrarrojos , Sondas Moleculares/química , Línea Celular TumoralRESUMEN
Alternations in the brain nitric oxide (NO) homeostasis are associated with a variety of neurodegeneration diseases; therefore, high-resolution imaging of NO in the brain is essential for understanding pathophysiological processes. However, currently available NO probes are unsuitable for this purpose due to their poor ability to cross the blood-brain barrier (BBB) or to image in deep tissues with spatial resolution. Herein, we developed a photoacoustic (PA) probe with BBB crossing ability to overcome this obstacle. The probe shows a highly selective ratiometric response toward NO, which enables the probe to image NO with micron resolution in the whole brain of living mice. Using three-dimensional PA imaging, we demonstrated that the probe could be used to visualize the detailed NO distribution in varying depth cross-sections (0-8 mm) of the living Parkinson's disease (PD) mouse brain. We also investigated the therapeutic properties of natural polyphenols in the PD mouse brain using the probe as an imaging agent and suggested the potential of the probe for screening therapeutic agents. This study provides a promising imaging agent for imaging of NO in the mouse brain with high resolution. We anticipate that these findings may open up new possibilities for understanding the biological functions of NO in the brain and the development of new imaging agents for the diagnosis and treatment of brain diseases.
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Barrera Hematoencefálica , Óxido Nítrico , Animales , Ratones , Encéfalo , Análisis Espectral , Imagenología TridimensionalRESUMEN
Cationic, water-soluble benzophenothiaziniums have been recognized as effective type I photosensitizers (PSs) against hypoxic tumor cells. However, the study of the structure-property relationship of this type of PS is still worth further exploration to achieve optimized photodynamic effects and minimize the potential side effects. Herein, we synthesized a series of benzophenothiazine derivatives with minor N-alkyl alteration to study the effects on the structure-property relationships. The cellular uptake, subcellular organelle localization, reactive oxygen species (ROS) generation, and photocytotoxicity performances were systematically investigated. NH2NBS and EtNBS specifically localized in lysosomes and exhibited high toxicity under light with a moderate phototoxicity index (PI) due to the undesirable dark toxicity. However, NMe2NBS with two methyl substitutions accumulated more in mitochondria and displayed an excellent PI value with moderate light toxicity and negligible dark toxicity. Without light irradiation, NH2NBS and EtNBS could induce lysosomal membrane permeabilization (LMP), while NMe2NBS showed no obvious damage to lysosomes. After irradiation, NH2NBS and EtNBS were released from lysosomes and relocated into mitochondria. All compounds could induce mitochondria membrane potential (MMP) loss and nicotinamide adenine dinucleotide phosphate (NADPH) consumption under light to cause cell death. NMe2NBS exhibited remarkable in vivo photodynamic therapy (PDT) efficacy in a xenograft mouse tumor (inhibition rate, 89%) with no obvious side effects. This work provides a valuable methodology to investigate the structure-property relationships of benzophenothiazine dyes, which is of great importance in the practical application of PDT against hypoxia tumor cells.
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Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Animales , Ratones , Fármacos Fotosensibilizantes/farmacología , Fenotiazinas , Alquilación , Fotoquimioterapia/métodos , Línea Celular TumoralRESUMEN
Biothiols, including glutathione (GSH), homocysteine (Hcy) and cysteine (Cys), play crucial roles in various physiological processes. Though an array of fluorescent probes have been designed to visualize biothiols in living organisms, few one-for-all imaging agents for sensing biothiols with fluorescence and photoacoustic imaging capabilities have been reported, since instructions for synchronously enabling and balancing every optical imaging efficacy are deficient. Herein, a new near-infrared thioxanthene-hemicyanine dye (Cy-DNBS) has been constructed for fluorescence and photoacoustic imaging of biothiols in vitro and in vivo. Upon treatment with biothiols, the absorption peak of Cy-DNBS shifted from 592 nm to 726 nm, resulting in a strong NIR absorption as well as a subsequent turn-on PA signal. Meanwhile, the fluorescence intensity increased instantaneously at 762 nm. Then, Cy-DNBS was successfully utilized for imaging endogenous and exogenous biothiols in HepG2 cells and mice. In particular, Cy-DNBS was employed for tracking biothiols upregulation in the liver of mice triggered by S-adenosyl methionine by means of fluorescent and photoacoustic imaging methods. We expect that Cy-DNBS serves as an appealing candidate for deciphering biothiols-related physiological and pathological processes.
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Cisteína , Neoplasias , Animales , Ratones , Colorantes Fluorescentes , Espectrometría de Fluorescencia , Imagen Óptica/métodos , Hígado , Glutatión , HomocisteínaRESUMEN
Spatiotemporal assessment of the oxidative stress dynamics in the brain is crucial for understanding the molecular mechanism underlying neurodegenerative diseases. However, existing oxidative stress probes have poor blood-brain barrier permeability or poor penetration depth, making them unsuitable for brain imaging. Herein, we developed a photoacoustic probe that enables real-time imaging of oxidative stress dynamics in the mouse brain. The probe not only responds to oxidative stress in a reversible and ratiometric manner, but it can also cross the blood-brain barrier of the mouse brain. Notably, the probe displayed excellent photoacoustic imaging of oxidative stress dynamics in the brains of Parkinson's disease mouse models. In addition, we investigated the antioxidant properties of natural polyphenols in the brain of a Parkinson's disease mouse model using the probe as an imaging agent and suggested the potential of the probe for screening anti-oxidative stress agents.
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Enfermedad de Parkinson , Técnicas Fotoacústicas , Ratones , Animales , Barrera Hematoencefálica , Encéfalo/diagnóstico por imagen , Análisis Espectral , Estrés Oxidativo , Técnicas Fotoacústicas/métodosRESUMEN
Ferroptosis is of great importance in physiological and pathological processes, which is associated with various inflammation-related diseases, cardiovascular diseases, and even cancer. Ferroptosis can cause abnormal change of reactive oxygen species (ROS) in mitochondria. Hypochlorous acid (HClO) acts as a typical ROS. Therefore, it is needed to study the relationship between mitochondrial morphology and HClO changes during ferroptosis at the subcellular level. To this end, a near-infrared-excitation/emission fluorescent probe, HD-Br-1, for rapid detection of mitochondrial HClO was developed based on the specific oxidative cleavage of the N,N-dimethylthiocarbamate moiety. The fluctuation in mitochondrial HClO content and the change in mitochondrial morphology during ferroptosis were monitored in real time by super-resolution imaging. In addition, HD-Br-1 was successfully applied to monitor exogenous and endogenous mitochondrial HClO during cell ferroptosis and visualize tumor to discriminate from healthy tissues. Therefore, we believe that HD-Br-1 could provide a valuable approach for the detection of mitochondrial HClO in cancer cells as well as for understanding the ferroptosis mechanism and early diagnosis of cancers associated with ferroptosis for future research.
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Ferroptosis , Colorantes Fluorescentes , Microscopía Fluorescente/métodos , Ácido Hipocloroso , MitocondriasRESUMEN
Triple-negative breast cancer (TNBC) is a serious health issue for women worldwide and there is still no suitable treatment option. AA005, a structurally simplified mimic of natural Annonaceous acetogenins, presents outstanding properties with impressive cytotoxicity and cell-type selective actions. The present study was aimed at evaluating the potential of AA005 as a therapeutic agent for TNBC. AA005 potently inhibited the growth of TNBC cells at 50â nM level. Inspired by the finding of the phosphatase and tensin homologue (PTEN) tumor suppressor, the effect of AA005 on aerobic glycolysis was investigated in TNBC MDA-MB-468 cells. A short-term AA005 exposure markedly suppressed mitochondrial function in MDA-MB-468 cells, thus activating the aerobic glycolysis to lessen the risk of decreased ATP generation in mitochondria. Prolonging the incubation time of AA005 clearly weakened the aerobic glycolysis in the cells. This was in part attributed to the PI3K-AKT pathway inactivation and subsequent declined glucose uptake. As a consequence, the energy supply was completely cut from the two major energy-producing pathways. Further experiments showed that AA005 resulted in irreversible damage on cell activity including cell cycle and growth, inducing mitochondrial oxidative stress and ultimately leading to cell death. In addition, the inâ vivo therapeutic efficacy of AA005 was proved on 4T1 xenograft tumor mice model. Our data demonstrate that AA005 exhibited a great potential for future clinical applications in TNBC therapy.
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Neoplasias de la Mama Triple Negativas , Acetogeninas/farmacología , Acetogeninas/uso terapéutico , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Metabolismo Energético , Alcoholes Grasos , Femenino , Humanos , Lactonas , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
Brain atlases enable the mapping of labeled cells and projections from different brains onto a standard coordinate system. We address two issues in the construction and use of atlases. First, expert neuroanatomists ascertain the fine-scale pattern of brain tissue, the 'texture' formed by cellular organization, to define cytoarchitectural borders. We automate the processes of localizing landmark structures and alignment of brains to a reference atlas using machine learning and training data derived from expert annotations. Second, we construct an atlas that is active; that is, augmented with each use. We show that the alignment of new brains to a reference atlas can continuously refine the coordinate system and associated variance. We apply this approach to the adult murine brainstem and achieve a precise alignment of projections in cytoarchitecturally ill-defined regions across brains from different animals.
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Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Biología Computacional/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Animales , Encéfalo/anatomía & histología , Tronco Encefálico/diagnóstico por imagen , Aprendizaje Automático , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas Motoras , Neuroanatomía , Neuronas , Probabilidad , Médula Espinal/diagnóstico por imagenRESUMEN
Organelle-targeted type I photodynamic therapy (PDT) shows great potential to overcome the hypoxic microenvironment in solid tumors. The endoplasmic reticulum (ER) is an indispensable organelle in cells with important biological functions. When the ER is damaged due to the production of reactive oxygen species (ROS), the accumulation of misfolded proteins will interfere with ER homeostasis, resulting in ER stress. Here, an ER-targeted benzophenothiazine-based photosensitizer NBS-ER was presented. ER targeting modification significantly reduced the dark toxicity and improved phototoxicity index (PI). NBS-ER could effectively produce O2 - â with near-infrared irradiation, making its phototoxicity under hypoxia close to that under normoxia. Meanwhile, the photoinduced ROS triggered ER stress and induced apoptosis. In addition, NBS-ER possessed excellent photodynamic therapeutic effect in 4T1-tumor-bearing mice.
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Neoplasias , Fotoquimioterapia , Animales , Ratones , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Fotoquimioterapia/métodos , Retículo Endoplásmico/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Hipoxia/metabolismo , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Specimen differences, tissue-dependent background fluorescence and scattering, and deviated specimen position and sensor concentration make optical imaging for labile copper fluctuation in animals questionable, and a signal comparison between specimens is infeasible. We proposed ratiometric optical imaging as an alternative to overcome these disadvantages, and a near-infrared (NIR) ratiometric sensor, BDPS1, was devised therefore by conjugating boron dipyrromethene (BODIPY) with 4-aminostyrene and modifying the 4-amino group as a Cu+ chelator. BDPS1 possessed an excitation ratiometric copper-sensing ability to show the ratio of NIR emission (710 nm) upon excitation at 600 nm to that at 660 nm, Fex600/Fex660, increasing from 2.8 to 10.7. This sensor displayed still the opposite copper response of its internal charge transfer (ICT; 670 nm) and local (581 nm) emission bands. Ratiometric imaging with this sensor disclosed a higher labile copper region near the nucleus apparatus, and HEK-293T cells were more sensitive to copper incubation than MCF-7 cells. Dual excitation ratiometric imaging with this sensor realized tracking of labile copper fluctuation in mice, and the whole-body imaging found that tail intravenous injection of CUTX-101, a therapeutical agent for Menkes disease, led to a distinct labile copper increase in the upper belly. The ex vivo imaging of the resected viscera of mice revealed that CUTX-101 injection enhanced the labile copper level in the liver, intestine, lung, and gall bladder in sequence, yet the kidney, heart, and spleen showed almost no response. This study indicated that modifying BODIPY as an extended ICT fluorophore, with its electron-donating group being derived as a metal chelator, is an effective design rationale of NIR ratiometric sensors for copper tracking in vivo/ex vivo.
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Porfobilinógeno/análogos & derivados , BoroRESUMEN
Limited therapeutic efficacy to hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy (PDT). Two new benzothiophenylisoquinoline (btiq)-derived cyclometalated IrIII complexes, IrL1 and MitoIrL2, were constructed as potent photosensitizers, with the latter being designed for mitochondria accumulation. Both complexes demonstrated a typeâ I PDT process and caused photoinduced ferroptosis in tumor cells under hypoxia. This ferroptosis featured lipid peroxide accumulation, mitochondria shrinkage, down-regulation of glutathione peroxidase 4 (GPX4), and ferrostatin-1 (Fer-1)-inhibited cell death. Upon photoirradiation under hypoxia, mitochondria targeting MitoIrL2 caused mitochondria membrane potential (MMP) collapse, ATP production suppression, and induced cell apoptosis. The synergetic effect of ferroptosis and apoptosis causes MitoIrL2 to outperform IrL1 in inhibiting the growth of MCF-7, PANC-1, MDA-MB-231 cells and multicellular spheroids. This study demonstrates the first example of ferroptosis induced by photosensitizing IrIII complexes. Moreover, the synergism of ferroptosis and apoptosis provides a promising approach for combating hypoxic solid tumors through typeâ I PDT processes.
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Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Ferroptosis/efectos de los fármacos , Iridio/farmacología , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Iridio/química , Procesos Fotoquímicos , Fármacos Fotosensibilizantes/químicaRESUMEN
Small organic photothermal agents (SOPTAs) that absorb in the second near-infrared (NIR-II, 1000-1700â nm) window are highly desirable in photothermal therapy for their good biocompatibility and deeper tissue penetration. However, the design of NIR-II absorbing SOPTAs remains a great challenge. Herein, we report that molecular engineering of BF2 complex via strengthening the donor-acceptor conjugation and increasing the intramolecular motions is an efficient strategy to achieve NIR-II absorbing SOPTAs with high photothermal performance. Based on this strategy, a BF2 complex, BAF4, was designed and synthesized. BAF4 exhibits an intense absorption maximum at 1000â nm and negligible fluorescence. Notably, the nanoparticles of BAF4 achieve a high photothermal conversion efficiency value of 80 % under 1064â nm laser irradiation (0.75â W cm-2 ). In vitro and in vivo studies reveal the great potential of BAF4 nanoparticles in photoacoustic imaging-guided photothermal therapy in the NIR-II window.
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Antineoplásicos/farmacología , Colorantes Fluorescentes/farmacología , Hidrocarburos Halogenados/farmacología , Fármacos Fotosensibilizantes/farmacología , Terapia Fototérmica , Animales , Antineoplásicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Colorantes Fluorescentes/química , Humanos , Hidrocarburos Halogenados/química , Rayos Infrarrojos , Ratones , Estructura Molecular , Fármacos Fotosensibilizantes/químicaRESUMEN
The generation of different thermodynamically (meta)stable states is crucial for the development of smart solid-state luminescent materials. However, the design of luminophores with tunable aggregation states is remaining a grand challenge. Herein, we present a family of mechanochromic luminophores with tunable metastable states, based on the dynamically controllable π-π stacking of the flexible π-conjugated structure of 2,5-diarylamino-terephthalates in the solid state. The experimental data revealed that both the kinetically controlled metastable state and thermodynamic controlled stable state can be generated via tuning the intermolecular interactions such as π-π stacking and hydrogen bonds. As a result, the highly sensitive mechano-stimuli response of these luminophores was successfully achieved.
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Real-time monitoring of hydrogen sulphide (H2S) level change is of crucial importance for the study of its complicated roles in physiology. Herein, we developed a FRET strategy for designing ratiometric fluorescent H2S sensors. A coumarin-derived merocyanine fluorophore was selected as the acceptor, and two green-light-emission fluorophores were introduced as donors. The sensing mechanism was based on tuning the FRET efficiency, and the free sensors exhibited strong near-infrared emission at 665 nm due to the FRET process. The nucleophilic addition of HS- to the imide carbon disrupts the large conjugation system of merocyanine, which induces a dramatic loss of its absorption; thus, the FRET process gets blocked, and the green emission is increased. In the aqueous solution, both the probes, NBD-CMC and Nap-CMC, showed ratiometric H2S sensing behaviour, fast response, and high selectivity and sensitivity. Moreover, probe NBD-CMC was successfully applied to monitor the fluctuation of exogenously and endogenously generated H2S in HepG-2 cells.
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Cumarinas/química , Colorantes Fluorescentes/química , Sulfuro de Hidrógeno/análisis , Indoles/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Células Hep G2 , Humanos , Sulfuro de Hidrógeno/química , Límite de Detección , Microscopía Confocal , Microscopía FluorescenteRESUMEN
Developing a ratiometric H2S fluorescent probe with fast response is of great importance for studying the H2S physiology. Herein, two hemicyanine-based H2S probes were constructed; the one with a propanoic acid group (CouPa) showed poor sensitivity while the other one with the N,N-diethylpropionamide moiety (CouDE) exhibited distinctly improved performance. CouDE showed the ability to detect mitochondrial H2S level fluctuation, which was triggered by alteration of CBS enzyme activity. Moreover, endogenous H2S change in solid tumours was monitored using CouDE.