RESUMO
The emergence of lipid droplets (LDs) has been recognized as cellular markers of ocular surface hyperosmosis, which is recognized as a fundamental mechanism driving dry eye disease (DED), while their dynamics during DED progression and therapy remains unlocked. For this purpose, an LD-specific fluorescent probe P1 is presented in this work that exhibits highly selective and sensitive emission enhancement in response to a decreased ambient polarity (Δf) from 0.209 to 0.021. The hydrophobic nature of P1 enables specific staining of LDs, facilitating visualization of changes in polarity within these cellular structures. Utilizing P1, we observe a decrease in polarity accompanied by an increase in the size and number of LDs in hyperosmotic human corneal epithelial cells (HCECs). Furthermore, interplays between LDs and cellular organelles such as mitochondria and the Golgi apparatus are visualized, suggesting the underlying pathogenesis in DED. Notably, the variations of LDs are observed after the inhibition of ferroptosis or activation of autophagy in hyperosmotic HCECs, implying the great potential of LDs as indicators for the design and efficacy evaluation of DED drugs regarding ferroptosis or autophagy as targets. Finally, LDs are confirmed to be overproduced in corneal tissues from DED mice, and the application of clinical eye drops effectively impedes these changes. This detailed exploration underscores the significant roles of LDs as an indicator for the deep insight into DED advancement and therapy.
Assuntos
Síndromes do Olho Seco , Corantes Fluorescentes , Gotículas Lipídicas , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/química , Humanos , Animais , Camundongos , Corantes Fluorescentes/química , Autofagia , FluorescênciaRESUMO
The diagnosis and treatment of breast cancer is of immense importance in improving patient outcomes. The biological marker NAD(P)H:quinone oxidoreductase 1 was utilized to design BrCyS-Q, a near-infrared activatable photosensitizer for breast cancer. BrCyS-Q was successfully employed to diagnose breast cancer cells using fluorescence and photodynamic inhibition. The findings of this research may offer novel insights for the diagnosis and treatment of clinical breast cancer via photodynamic therapy.
Assuntos
Neoplasias da Mama , Fotoquimioterapia , Humanos , Feminino , Fármacos Fotossensibilizantes/farmacologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Quinonas , FluorescênciaRESUMO
As an important member of dyes, small-molecule fluorescent dyes show indispensable value in biomedical fields. Although various molecular dyes have been developed, full-color dyes covering blue to red region derived from a single chromophore are still in urgent demand. In this work, a series of dyes based on C2-alkenyl indole skeleton were synthesized, namely AI dyes, and their photophysical properties, cytotoxicity, and imaging capacity were verified to be satisfactory. Particularly, the maximal emission wavelengths of these dyes could cover a wide range from visible to NIR light with large Stokes shifts. Besides, the optical and structural discrepancies between the C2- and C3- alkenyl AI dyes were discussed in detail, and the theoretical calculations were conducted to provide insights on such structure-activity relationship. Finally, as a proof-of-concept, a fluorescent probe AI-Py-B capable of imaging endogenous ONOO- was presented, demonstrating the bioimaging potentials of these alkenyl indole dyes. This work is anticipated to open up new possibilities for developing dye engineering and bio-applications of natural indole framework.
Assuntos
Corantes Fluorescentes , Indóis , Imagem Óptica/métodos , Compostos RadiofarmacêuticosRESUMO
Pancreatic cancer (PC) is one of the most lethal cancers worldwide, which is usually diagnosed in the advanced stage and is highly resistant to traditional chemotherapy, radiotherapy, and immunotherapy. Therefore, there is an urgent need for developing new PC-specific imaging and treatment. In this study, an quinone oxidoreductase 1 (NQO-1)-activated near-infrared (NIR) agent, ICy-Q, was synthesized. ICy-Q is almost nonemissive, while its NIR emission at 705 nm is triggered by NQO-1-induced reduction in the PC cells. In addition, the reduction product, ICy-OH, is specifically enriched in mitochondria and lysosomes and acts as an effective chemotherapeutic agent to selectively induce pancreatic cancer cell death via the cell pyroptosis pathway. Further studies have shown that ICy-Q is suitable for ex vivo imaging of clinical PC sections and solid tumors from patients. We expect this study will be helpful in the future for the design of targeted theranostic agents for PC.
Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Medicina de Precisão , Nanomedicina Teranóstica/métodos , Neoplasias PancreáticasRESUMO
Abnormal microenvironments (viscosity, polarity, pH, etc.) have been verified to be closely associated with numerous pathophysiological processes such as inflammation, neurodegenerative diseases, and cancer. As a result, deep insights into these pathophysiological microenvironments are particularly beneficial for clinical diagnosis and treatment. However, the monitoring of pathophysiological microenvironments is unattainable by the traditional clinical diagnostic techniques such as magnetic resonance imaging, computed tomography, and positron emission tomography. Recently, fluorescence imaging has shown tremendous advantages and potential in the tracing of pathophysiological microenvironment variations. In this context, a general discussion is provided on the state-of-the-art progress of fluorescent probes for visualizing pathophysiological microenvironments (viscosity, pH, and polarity), since 2016, as well as the future perspectives in this challenging field.
Assuntos
Microambiente Celular , Corantes Fluorescentes/análise , Imagem Óptica , Animais , FluorescênciaRESUMO
A fluorescent chemosensor has been developed for discriminative detection of phosgene and a nerve agent mimic diethyl chlorophosphate (DCP), which was comprised of an anthracene-carboxyimide fluorophore and o-phenylenediamine (OPD) reaction site. Upon phosphorylation of OPD, the chemosensor displays an obvious fluorescence turn-on response toward DPC at 588 nm with instant response and a low detection limit (88 nM). By contrast, the chemosensor exhibits a colorimetric and fluorescence enhancement response at 500 nm toward phosgene with fast response (<2 min), high selectivity, and a low detection limit (72 nM). Furthermore, chemosensor-loaded test membrane was fabricated for real-time, portable and efficient discriminative detection of trace amounts of gaseous phosgene and DCP vapor with different optical responses.
Assuntos
Corantes Fluorescentes/química , Agentes Neurotóxicos/análise , Compostos Organofosforados/análise , Fosgênio/análise , Antracenos/química , Imidas/química , Estrutura Molecular , Fenilenodiaminas/química , Espectrometria de FluorescênciaRESUMO
Protons play crucial roles in many physiological and pathological processes, such as receptor-mediated signal transduction, ion transport, endocytosis, homeostasis, cell proliferation, and apoptosis. The urgent demand for pH imaging and measurement in biological systems has incited the development of fluorescent pH probes. Numerous fluorescent probes have been reported, but many lack the abilities needed for biological applications. Hence, the development of new pH probes with better biocompatibility, sensitivity, and site-specificity is still indispensable. This review highlights the recent trends in the development of fluorescent materials as essential tools for tracing pH variations in the biological processes of diverse living systems.
Assuntos
Corantes Fluorescentes/química , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Animais , Linhagem Celular , Microambiente Celular , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Nanopartículas , Transdução de Sinais , Relação Estrutura-AtividadeRESUMO
The first triazole-containing fluorescent probe with excellent water-solubility for Pd(2+) was presented. The results indicated that an amide-triazole-amide binding sequence was responsible for the unique affinity of PS-1 toward Pd(2+). Among the tested metal ions, only Pd(2+) could selectively quench the fluorescence of PS-1 under physiological conditions, while other common interference ions like Pt(2+) and Ru(3+) caused little changes. The successful fluorescence imaging of Pd(2+) in HeLa cells implied the potential applications of PS-1 in biological Pd(2+)-analysis.
RESUMO
A dianthracene-cyclen conjugate was synthesized via 'click' chemistry, which could serve as an equal-equivalent responding chemosensor for Pb(2+) in aqueous solution. Moreover, it could be successfully applied in the detection of Pb(2+) in living cells and fetal calf serum.
Assuntos
Antracenos/química , Compostos Heterocíclicos/química , Chumbo/análise , Poluentes Químicos da Água/análise , Poluição da Água/análise , Ciclamos , Chumbo/química , Espectrometria de Massas , Espectrometria de FluorescênciaRESUMO
An ensemble-based fluorescent sensor HS-1 + Cu(2+) for detection of histidine is reported. Complex HS-1 + Cu(2+) sensitively senses histidine at pH 7.4 in aqueous media. The quantitative determination of histidine in urine and fetal calf serum is also conducted.
Assuntos
Aminas/química , Cobre/química , Cumarínicos/química , Corantes Fluorescentes/química , Histidina/sangue , Histidina/urina , Ácidos Picolínicos/química , Animais , Humanos , Sensibilidade e Especificidade , Espectrometria de Fluorescência/métodosRESUMO
Hydrogen sulfide (H2S), as an important endogenous signaling molecule, plays a vital role in many physiological processes. The abnormal behaviors of hydrogen sulfide in organisms may lead to various pathophysiological processes. Monitoring the changes in hydrogen sulfide is helpful for pre-warning and treating these pathophysiological processes. Fluorescence imaging techniques can be used to observe changes in the concentration of analytes in organisms in real-time. Therefore, employing fluorescent probes imaging to investigate the behaviors of hydrogen sulfide in pathophysiological processes is vital. This paper reviews the design strategy and sensing mechanisms of hydrogen sulfide-based fluorescent probes, focusing on imaging applications in various pathophysiological processes, including neurodegenerative diseases, inflammation, apoptosis, oxidative stress, organ injury, and diabetes. This review not only demonstrates the specific value of hydrogen sulfide fluorescent probes in preclinical studies but also illuminates the potential application in clinical diagnostics.
RESUMO
Diabetic cataract (DC) surgery carries risks such as slow wound healing, macular edema, and progression of retinopathy and is faced with a deficiency of effective drugs. In this context, we proposed a protocol to evaluate the drug's efficacy using lipid droplets (LDs) as the marker. For this purpose, a fluorescent probe PTZ-LD for LDs detection is developed based on the phenothiazine unit. The probe displays polarity-dependent emission variations, i.e., lower polarity leading to stronger intensity. Especially, the probe exhibits photostability superior to that of Nile Red, a commercial LDs staining dye. Using the probe, the formation of LDs in DC-modeled human lens epithelial (HLE) cells is validated, and the interplay of LDs-LDs and LDs-others are investigated. Unexpectedly, lipid transfer between LDs is visualized. Moreover, the therapeutic efficacy of various drugs in DC-modeled HLE cells is assessed. Ultimately, more LDs were found in lens epithelial tissues from DC patients than in cataract tissues for the first time. We anticipate that this work can attract more attention to the important roles of LDs during DC progression.
Assuntos
Catarata , Diabetes Mellitus , Humanos , Gotículas Lipídicas , Células HeLa , Células Epiteliais , Imagem ÓpticaRESUMO
A multifunctional fluorescent sensor based on a cyclen-appended BINOL derivative (R-1) was synthesized and characterized. It can display on-off-type fluorescence change with high selectivity toward Cu(II) among 19 metal ions in 100% aqueous solution. Furthermore, the in situ generated R-1-Cu(II) ensemble could recover the quenched fluorescence upon the addition of sulfide anion resulting in a off-on-type sensing with a detection limit of micromolar range in the same medium. No interference was observed from other biothiols and anions, including GSH, l-Cys, DTT, and sulfates, making it a highly sensitive and selective sulfide probe.
Assuntos
Ânions/química , Cobre/química , Naftóis/química , Compostos de Sulfidrila/química , Sulfetos/química , Fluorescência , Estrutura Molecular , Espectrometria de Fluorescência , ÁguaRESUMO
A reaction-based colorimetric and ratiometric fluorescent probe based on an ICT-strategy for selective detection of H(2)S that exploited the H(2)S-mediated reduction of nitrocompound to amines was explored. And it displayed high selectivity for H(2)S over other relevant reactive sulfur, oxygen, nitrogen species and other anions with more than 120 nm blue shift and the change of emission intensity ratio inducted by H(2)S was over 4750.
Assuntos
Colorimetria/instrumentação , Corantes Fluorescentes/química , Sulfeto de Hidrogênio/análise , Aminas/química , Corantes Fluorescentes/síntese química , Estrutura Molecular , OxirreduçãoRESUMO
Currently, the role of the lysosome, endoplasmic reticulum, or dictyosome in the transcription and translation of programmed cell death ligand 1 (PD-L1) is well revealed, but the role and function of mitochondria in the PD-L1 expression in tumors is still not fully researched, making it hard to offer a novel PD-L1 regulation strategy. In this research, it is newly revealed that mitochondria oxidative phosphorylation (OXPHOS) depression can be used as an effective PD-L1 down-regulation method. To offer an ideal and high-effective tumor mitochondria-targeted OXPHOS depression nanosystem, IR-LND is prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68 with mitochondrial complexes I and II depression agent lonidamine (LND), which then further self-assembled with albumin (Alb) to form IR-LND@Alb nanoparticles. By doing this, PD-L1 expression in tumors is selectively and effectively depressed by IR-LND@Alb nanoparticles. As expected, the anti-tumor efficacy of such a PD-L1 depression strategy is superior to conventional anti-PD-L1 monoclonal antibodies. Interestingly, IR-LND can also be served as a novel ideal promising photodynamic therapy (PDT) drug with self-oxygen and self-PD-L1 regulation capacity. All in all, this tumor-selective metabolic reprogramming platform to reactivate immunotherapy and sensitize for PDT effect, would open a new window for mitochondrial immunotherapy for cancer patients.
Assuntos
Neoplasias , Receptor de Morte Celular Programada 1 , Albuminas , Anticorpos Monoclonais , Antígeno B7-H1/metabolismo , Carbocianinas , Linhagem Celular Tumoral , Depressão , Humanos , Fatores Imunológicos , Imunoterapia , Ligantes , Neoplasias/tratamento farmacológico , Oxigênio , Receptor de Morte Celular Programada 1/metabolismo , Estudos ProspectivosRESUMO
Diagnosis of diabetic cataract (DC) in the early stage is of great significance for drug intervention and surgery circumvention for DC patients. However, the lack of reliable imaging tools greatly limits the diagnosis of early DC. In this context, a fluorescent probe BBPy for hypochlorous acid (HOCl) is presented based on the oxidation of phenothiazine. The probe displays apparent emission enhancement at 562 nm toward HOCl with high selectivity, superb sensitivity (detection limit: 12.6 nM), and rapid response (within seconds). Using the probe, the HOCl generation in diabetic human lens epithelial cells was monitored, as well as the HOCl down-regulation during antioxidant treatment. Therefore, it is proposed that HOCl can be a promising biomarker for DC and fluorescence imaging technique can be regarded as a candidate tool for DC diagnosis.
Assuntos
Catarata , Diabetes Mellitus , Corantes Fluorescentes , Humanos , Ácido Hipocloroso , Imagem Óptica , OxirreduçãoRESUMO
We present a ratiometric fluorescent probe for monitoring pH featuring superb photostability and chemostability. The down-regulation of the intracellular pH during autophagy in living cells induced by various stimuli, including several drugs and starvation, was quantified, which could provide instructive value to construct autophagy models to study the related pathological processes.
Assuntos
Autofagia/fisiologia , Cumarínicos/química , Corantes Fluorescentes/química , Piridinas/química , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Concentração de Íons de Hidrogênio , Estrutura MolecularRESUMO
The early diagnosis of osteoarthritis (OA) can halt or delay the progression of the disease, and it is essentially beneficial to its treatment. However, biomarkers with sufficient sensitivity for dynamically identifying early OA are still yet to be determined. The overproduced hypochlorous acid (HOCl) has been proposed as an obvious symptom in early OA. Herein, based on the oxidation reaction of the sulfur atom in phenothiazine into sulfoxide, we design and synthesize a phenothiazine-derived coumarin fluorescent probe PDC for the detection of ClO- in cells and in an OA mouse model. The probe PDC exhibits excellent selectivity and sensitivity for ClO- detection with a limit of detection as low as 16.1 nM. Taking advantage of the probe PDC, we visualize and evaluate the level changes of ClO- in macrophage cells, which is stimulated by various inflammatory factors. The anti-inflammatory and therapeutic effects of selenocysteine and methotrexate in inflamed cells are also confirmed. Finally, with in vivo imaging of ClO- concentration changes in OA BALB/c mouse models, we successfully inspected the relationship between OA phenotypes and the burst of ClO-. We suggest that abnormal changes in HOCl concentration may be considered as a new biomarker for the early OA diagnosis.
Assuntos
Ácido Hipocloroso , Sondas Moleculares , Osteoartrite , Animais , Corantes Fluorescentes , Camundongos , Camundongos Endogâmicos BALB C , Osteoartrite/diagnóstico , Osteoartrite/tratamento farmacológicoRESUMO
We describe a colorimetric and fluorescent probe 3a to detect cellular peroxynitrite with high selectivity and sensitivity. 3a was successfully applied in the bioimaging of exogenous and endogenous peroxynitrite in living cells. The up-regulation of peroxynitrite in cancer cells and normal cells during 5-fluorouracil treatment was finally monitored.
Assuntos
Antineoplásicos/farmacologia , Corantes Fluorescentes/farmacologia , Fluoruracila/farmacologia , Ácido Peroxinitroso/biossíntese , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/química , Fluoruracila/química , Humanos , Células MCF-7 , Estrutura Molecular , Imagem Óptica , Ácido Peroxinitroso/química , Relação Estrutura-AtividadeRESUMO
A chemosensor containing an o-hydroxyaniline unit as the reaction site was developed for colorimetric and fluorimetric detection of phosgene, which showed fast response (15 s), high specificity, and an extremely low detection limit. The chemosensor was incorporated into paper strips for visual detection of phosgene vapor.