RESUMO
Biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) play important roles in various physiological and pathological processes, and due to their similar structures and reaction activities, it is still challenging to simultaneously discriminate between GSH and Cys/Hcy in vivo. Hence, a novel fluorescent probe for simultaneously discriminating GSH and Cys/Hcy in biological samples is highly desirable. Herein, we presented two enhanced fluorescent probes (Cy1 and Cy2) with doubly-activated dual emission for sensitive and discriminative detection of Cys/Hcy and GSH. The probes were constructed with IR-780 and NBD linked via an ether bond, which responds to GSH with near infrared (NIR) emission at 810 nm (λex = 720 nm) and Cys/Hcy with visible green emission at 550 nm (λex = 470 nm). The probe Cy2 is operable in human serum samples, thus holding promise for its diagnosis-related application. Notably, the results of fluorescence microscopy imaging indicated that Cy2 is suitable for visualization of exogenous and endogenous biothiols in living cells. Furthermore, desirable results were obtained when the probe Cy2 was applied for bioimaging in tumor-bearing mice and acute liver injury (ALI) mice models, which revealed encouraging clinical values of this probe.
Assuntos
Cisteína , Diagnóstico por Imagem , Corantes Fluorescentes , Animais , Glutationa , Células HeLa , Homocisteína , Humanos , Camundongos , Microscopia de FluorescênciaRESUMO
As an over-expressed flavoprotein in several kinds of tumor cells, NAD(P)H: quinone oxidoreductase-1 (NQO1) is considered as a potent biomarker in early-stage cancer diagnosis. Developing a fast, selective and sensitive method of monitoring NQO1 on cellular level will greatly promote cancer diagnosis in clinical practice. In this paper, a fast NQO1 responsive fluorescence probe SYZ-30 containing quinone acid and 7-nitro-2,1,3-benzoxadiazole (NBD) fluorophore is constructed. The probe could selectively respond to NQO1 and rapidly emit strong fluorescence in vitro within only 5â¯min. Notably, the peak fluorescent intensities at 550â¯nm showed a linear relationship with NQO1 concentrations in the range of 3-30â¯ng/ml and limit of detection (LOD) was 0.0667â¯ng/ml. Furthermore, it was validated that the probe has good biocompatibility and could be applied for bio-imaging in NQO1 over-expressed cancer cells, together with its mitochondria targeting ability. Importantly, confocal fluorescence imaging confirmed the NQO1 detection ability on cellular level, which can be used for real-time detection of several cancer subtypes like adenocarcinoma. To conclude, the probe is rapidly responsive, highly sensitive and selective which will potentially become a practical tool for early cancer detection and diagnosis.
Assuntos
Corantes Fluorescentes/química , NAD(P)H Desidrogenase (Quinona)/análise , Neoplasias/diagnóstico por imagem , Imagem Óptica , Corantes Fluorescentes/síntese química , Humanos , Células Tumorais CultivadasRESUMO
Correction for 'A tumor-targeting probe based on a mitophagy process for live imaging' by Lijuan Gui et al., Chem. Commun., 2018, 54, 9675-9678.
RESUMO
The development of tumor-associated, stimuli-driven, turn-on near-infrared (NIR) fluorophores requires urgent attention because of their potential in selective and precise tumor diagnosis. Herein, we describe a NIR fluorescent probe (CyA-cRGD) comprised of a fluorescence reporting unit (a cyanine dye) linked with a GSH-responsive unit (nitroazo aryl ether group) and a tumor-targeting unit (cRGD). The NIR fluorescence of CyA-cRGD with sensitive and selective response to GSH can act as a direct off-on signal reporter for GSH monitoring. Notably, CyA-cRGD possesses improved biocompatibility compared with CyA, which is highly desirable for in vivo fluorescence tracking of cancer. Confocal fluorescence imaging confirmed the tumor-targeting capability and GSH detection ability of CyA-cRGD in tumor cells, normal cells, and coincubated tumor /normal cells and in the three-dimensional multicellular tumor spheroid. Furthermore, it was validated that CyA-cRGD could detect tumor precisely in GSH and integrin αvß 3 high-expressed tumor-bearing mouse models. Importantly, it was confirmed that CyA-cRGD possessed high efficiency for early-stage tumor imaging in mouse models with tumor cells implanted within 72 h. This method provided significant advances toward more in-depth understanding and exploration of tumor imaging, which may potentially be applied for clinical early tumor diagnosis.
Assuntos
Corantes Fluorescentes/química , Glutationa/metabolismo , Integrina alfaVbeta3/metabolismo , Neoplasias/diagnóstico , Animais , Modelos Animais de Doenças , Corantes Fluorescentes/metabolismo , Raios Infravermelhos , CamundongosRESUMO
Selective and efficient detection and imaging of nitroreductase (NTR) overexpressed in hypoxic tissues is of great importance for better understanding its biological functions. The effective optical probes equipped for NTR detection in vivo is still lacking, so we developed an innovative near infrared (NIR) fluorescent on-off probe (Cy-NO2) composed of fluorescence reporting unit (an aminocyaine dye) and recognition unit (p-nitrobenzylcarbamate group). The response and mechanism of the NTR activated reduction of Cy-NO2 were evaluated in vitro through kinetic optical studies, mass spectra analysis and docking calculations. The results demonstrated that Cy-NO2 could rapidly recognize NTR with high selectivity and sensitivity. The efficient NTR detection ability of Cy7-NO2 was further validated by fluorescence imaging of hypoxic cells (A549, PC-12 and HUVEC cell). Furthermore, the in vivo hypoxia imaging by Cy-NO2 were evaluated on tumor-bearing mouse, cerebral ischemia (CIS) and deep vein thrombosis models. The results indicated a rapid and distinct enhancement of its NIR fluorescence highly appropriate for in vivomonitoring of NTR in all of the three animal models, which revealed aspiring clinical value of this NIR fluorescent hypoxia probe.
Assuntos
Técnicas Biossensoriais/métodos , Microscopia de Fluorescência/métodos , Nitrorredutases/metabolismo , Imagem Óptica/métodos , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Corantes Fluorescentes/metabolismo , Raios Infravermelhos , Camundongos , Microscopia de Fluorescência/instrumentação , Imagem Óptica/instrumentação , Imagem Óptica/normasRESUMO
A glucosamine modified near-infrared cyanine dye CyT sensitive to pH was synthesized. Due to the different pH values of mitochondria and autolysosomes, the probe can simultaneously investigate mitochondria and autolysosomes in living cells. Moreover, due to the introduction of glucosamine groups, this fluorescent probe can be applied for tumor targeted imaging.
Assuntos
Corantes Fluorescentes/farmacologia , Glucosamina/análogos & derivados , Glucosamina/farmacologia , Indóis/farmacologia , Mitofagia , Neoplasias/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Glucosamina/síntese química , Glucosamina/química , Humanos , Concentração de Íons de Hidrogênio , Indóis/síntese química , Indóis/química , Lisossomos/metabolismo , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Mitocôndrias/metabolismo , Mitocôndrias/fisiologiaRESUMO
Development of photothermal agents for imaging-guided photothermal therapy (PTT) has been of great interest in the field of nanomedicine. CuS-apoferritin was prepared by a biomimetic synthesis method by using the inside cavity of apoferritin to control the size of CuS nanoparticles. Then, a water-soluble near infrared (NIR) dye (MBA) was bound with CuS-apoferritin, forming a nanocomplex (CuS-apoferritin-MBA) with greatly enhanced photothermal conversion efficiency compared to CuS-apoferritin. The unique optical behavior of CuS-apoferritin-MBA enables fluorescence imaging and photothermal therapy at separated optical wavelengths both, with optimized performances. CuS-apoferritin-MBA was then utilized as a photothermal agent for imaging-guided photothermal therapy in tumor-bearing mouse models. As revealed by in vivo fluorescence imaging, CuS-apoferritin-MBA showed high tumor uptake owing to an enhanced permeability and retention effect and the active targeting of apoferritin. In vivo photothermal therapy experiments indicated that tumors could be ablated by combining CuS-apoferritin-MBA with irradiation of an 808 nm laser. Thus, our work presents a safe, simple photothermal nanocomplex, promising for future clinical translation in cancer treatment.