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BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.
Asunto(s)
Biotina , Glutatión , Técnicas Fotoacústicas , Fotoquimioterapia , Glutatión/química , Glutatión/metabolismo , Animales , Humanos , Ratones , Biotina/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Imagen Óptica , Femenino , Terapia Fototérmica , Ratones Desnudos , Ratones Endogámicos BALB C , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
A near-infrared fluorescent probe (TX-P) for detecting peroxynitrite is constructed. The probe has a near-infrared emission (725 nm), large Stokes shift (125 nm) and excellent sensitivity and selectivity. In addition, TX-P can be used to visualize ONOO- in living cells, image ONOO- in paw edema mice and evaluate anti-inflammatory drugs.
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Edema , Colorantes Fluorescentes , Ácido Peroxinitroso , Animales , Ácido Peroxinitroso/metabolismo , Ácido Peroxinitroso/análisis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Ratones , Edema/diagnóstico por imagen , Edema/tratamiento farmacológico , Edema/inducido químicamente , Rayos Infrarrojos , Humanos , Imagen Óptica , Células RAW 264.7 , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/uso terapéuticoRESUMEN
Nitroreductase (NTR) overexpression often occurs in tumors, highlighting the significance of effective NTR detection. Despite the utilization of various optical methods for this purpose, the absence of an efficient tumor-targeting optical probe for NTR detection remains a challenge. In this research, a novel tumor-targeting probe (Cy-Bio-NO2) is developed to perform dual-modal NTR detection using near-infrared fluorescence and photoacoustic techniques. This probe exhibits exceptional sensitivity and selectivity to NTR. Upon the reaction with NTR, Cy-Bio-NO2 demonstrates a distinct fluorescence "off-on" response at 800 nm, with an impressive detection limit of 12 ng/mL. Furthermore, the probe shows on-off photoacoustic signal with NTR. Cy-Bio-NO2 has been successfully employed for dual-modal NTR detection in living cells, specifically targeting biotin receptor-positive cancer cells for imaging purposes. Notably, this probe effectively detects tumor hypoxia through dual-modal imaging in tumor-bearing mice. The strategy of biotin incorporation markedly enhances the probe's tumor-targeting capability, facilitating its engagement in dual-modal imaging at tumor sites. This imaging capacity holds substantial promise as an accurate tool for cancer diagnosis.
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Colorantes Fluorescentes , Nitrorreductasas , Imagen Óptica , Animales , Humanos , Ratones , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Neoplasias/diagnóstico por imagen , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/metabolismo , Nitrorreductasas/metabolismo , Nitrorreductasas/análisis , Técnicas Fotoacústicas , Dióxido de Nitrógeno/síntesis química , Dióxido de Nitrógeno/químicaRESUMEN
Cancer cells have a high abundance of hypochlorite compared to normal cells, which can be used as the biomarker for imaging cancer cells and tumor. Developing the tumor-targeting fluorescent probe suitable for imaging hypochlorite in vivo is urgently demanded. In this article, based on xanthene dye with a two-photon excited far-red to NIR emission, a tumor-targeting two-photon fluorescent probe (Biotin-HClO) for imaging basal hypochlorite in cancer cells and tumor was developed. For ClO-, Biotin-HClO (20.0 µM) has a linear response range from 15.0 × 10-8 to 1.1 × 10-5 M with a high selectivity and a high sensitivity, a good detection limit of 50 nM and a 550-fold fluorescence enhancement with high signal-to-noise ratio (20 mM PBS buffer solution with 50 % DMF; pH = 7.4; λex = 605 nm; λem = 635 nm). Morover, Biotin-HClO exhibited excellent performance in monitoring exogenous and endogenous ClO- in cells, and has an outstanding tumor-targeting ability. Subsequently, Biotin-HClO has been applied for imaging ClO- in 4T1 tumor tissue to distinguish from normal tissue. Furthermore, Biotin-HClO was successfully employed for high-contrast imaging 4T1 tumor in mouse based on its tumor-targeting ability. All these results proved that Biotin-HClO is a useful analytical tool to detect ClO- and image tumor in vivo.
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Colorantes Fluorescentes , Ácido Hipocloroso , Fotones , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Ácido Hipocloroso/análisis , Animales , Humanos , Ratones , Imagen Óptica , Biotina/química , Femenino , Ratones Endogámicos BALB C , Línea Celular Tumoral , Rayos InfrarrojosRESUMEN
Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.
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Compuestos de Anilina , Hígado Graso , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Animales , Viscosidad , Ratones , Hígado Graso/diagnóstico por imagen , Hígado Graso/tratamiento farmacológico , Compuestos de Anilina/química , Imagen Óptica , Humanos , Benzopiranos/química , Benzopiranos/síntesis química , Nitrilos/químicaRESUMEN
Ferroptosis modulation is a powerful therapeutic option for pancreatic ductal adenocarcinoma (PDAC) with a low 5-year survival rate and lack of effective treatment methods. However, due to the dual role of ferroptosis in promoting and inhibiting pancreatic tumorigenesis, regulating the degree of ferroptosis is very important to obtain the best therapeutic effect of PDAC. Biothiols are suitable as biomarkers of imaging ferroptosis due to the dramatic decreases of biothiol levels in ferroptosis caused by the inhibited synthesis pathway of glutathione (GSH) and the depletion of biothiol by reactive oxygen species. Moreover, a very recent study reported that cysteine (Cys) depletion can lead to pancreatic tumor ferroptosis in mice and may be employed as an effective therapeutic strategy for PDAC. Therefore, visualization of biothiols in ferroptosis of PDAC will be helpful for regulating the degree of ferroptosis, understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis, and further promoting the study and treatment of PDAC. Herein, two biothiol-activable near-infrared (NIR) fluorescent/photoacoustic bimodal imaging probes (HYD-BX and HYD-DX) for imaging of pancreatic tumor ferroptosis were reported. These two probes show excellent bimodal response performances for biothiols in solution, cells, and tumors. Subsequently, they have been employed successfully for real-time visualization of changes in concentration levels of biothiols during the ferroptosis process in PDAC cells and HepG2 cells. Most importantly, they have been further applied for bimodal imaging of ferroptosis in pancreatic cancer in mice, with satisfactory results. The development of these two probes provides new tools for monitoring changes in concentration levels of biothiols in ferroptosis and will have a positive impact on understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis and further promoting the study and treatment of PDAC.
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Ferroptosis , Colorantes Fluorescentes , Imagen Óptica , Neoplasias Pancreáticas , Técnicas Fotoacústicas , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Humanos , Colorantes Fluorescentes/química , Animales , Ratones , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/metabolismo , Rayos Infrarrojos , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologíaRESUMEN
As a basic parameter of the intracellular microenvironment, viscosity is closely related to the development of cancer. Thus, it is necessary to utilize a sensitive tool to visualize the viscosity in tumor cells and mice, which is helpful for the diagnosis of cancer. Herein, a novel dual-modal probe (IX-V) that has a near-infrared fluorescence (NIRF) and photoacoustic (PA) response to viscosity is synthesized. In low viscosity media, the probe has no fluorescence. With the increase of viscosity, the fluorescence is produced in the near-infrared region due to the inhibition of the TICT process. At the same time, the probe shows different photoacoustic (PA) signals in different viscosity media. Most notably, the viscosity in tumor cells has been imaged successfully by the application of IX-V, and the probe can effectively distinguish cancer cells from normal cells co-cultured in one dish by the difference of fluorescence intensity. In addition, the probe has been used for dual-modal imaging (NIRF and PA) of viscosity in tumor mice, which provides a tool for exploring the relationship between viscosity and diseases. That is to say, IX-V can achieve complementary imaging effects and has great application prospects in the tumor diagnosis.
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Colorantes Fluorescentes , Neoplasias , Ratones , Animales , Viscosidad , Línea Celular Tumoral , Fluorescencia , Imagen Óptica/métodos , Neoplasias/diagnóstico por imagenRESUMEN
Cysteine is an important biological thiol and is closely related to cancer. It remains a challenge to develop a probe that can provide long-term fluorescence detection and imaging of Cys in cells as well as in living organisms. Here, a solid-state fluorophore HTPQ is combined with an acrylate group to construct a solid-state fluorescent probe HTPQC for Cys recognition. The fluorescence of the probe is quenched when the photoinduced electron transfer (PET) process is turned on and the excited-state intramolecular proton transfer (ESIPT) process is turned off. In the presence of Cys, an obvious solid-state fluorescence signal can be observed. The double quenching mechanism makes the probe HTPQC have the advantages of high sensitivity, good selectivity, and high contrast of biological imaging. Due to low cytotoxicity, the probe HTPQC can be used to detect exogenous and endogenous Cys in living cells and is capable of imaging over long periods of time. By making full use of long wavelengths, the probe can be applied for the detection of Cys levels in tumor mice and equipped with the ability to conduct long-term imaging in vivo.
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Cisteína , Colorantes Fluorescentes , Humanos , Animales , Ratones , Colorantes Fluorescentes/toxicidad , Células HeLa , Compuestos de Sulfhidrilo , ProtonesRESUMEN
Although hydrogen sulfide (H2S) is a well-known toxic gas, its vital role as a gas transmitter in various physiological and pathological processes of living systems cannot be ignored. Relevant investigations indicate that endogenous H2S is involved in the development of ulcerative colitis pathology and is overexpressed in ulcerative colitis, and hence can be considered as an ulcerative colitis biomarker. Herein, an isophorone-xanthene-based NIR fluorescent probe (IX-H2S) was constructed to image H2S. Owing to its large conjugated structure, the probe exhibits a near-infrared emission wavelength of 770 nm with a large Stokes shift (186 nm). Moreover, IX-H2S has excellent selectivity for the detection of H2S without interference from other analytes including thiols. In addition, the probe has been successfully applied not only in fluorescence imaging of endogenous and exogenous H2S in living cells, but also in imaging of H2S in normal and ulcerative colitis mice. Encouraged by the eminent performance, IX-H2S is expected to be a potent "assistant" for the diagnosis of ulcerative colitis.
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Colitis Ulcerosa , Sulfuro de Hidrógeno , Humanos , Ratones , Animales , Colorantes Fluorescentes/toxicidad , Colorantes Fluorescentes/química , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/diagnóstico , Células HeLa , Mitocondrias , Imagen ÓpticaRESUMEN
Bioimaging is widely used in various fields of modern medicine. Fluorescence imaging has the advantages of high sensitivity, high selectivity, noninvasiveness, in situ imaging, and so on. However, one-photon (OP) fluorescence imaging has problems, such as low tissue penetration depth and low spatiotemporal resolution. These disadvantages can be solved by two-photon (TP) fluorescence imaging. However, TP imaging still uses fluorescence intensity as a signal. The complexity of organisms will inevitably affect the change of fluorescence intensity, cause false-positive signals, and affect the accuracy of the results obtained. Fluorescence lifetime imaging (FLIM) is different from other kinds of fluorescence imaging, which is an intrinsic property of the material and independent of the material concentration and fluorescence intensity. FLIM can effectively avoid the fluctuation of TP imaging based on fluorescence intensity and the interference of autofluorescence. Therefore, based on silica-coated gold nanoclusters (AuNCs@SiO2) combined with nucleic acid probes, the dual-mode nanoprobe platform was constructed for TP and FLIM imaging of intracellular endogenous miRNA-21 for the first time. First, the dual-mode nanoprobe used a dual fluorescence quencher of BHQ2 and graphene oxide (GO), which has a high signal-to-noise ratio and anti-interference. Second, the dual-mode nanoprobe can detect miR-21 with high sensitivity and selectivity in vitro, with a detection limit of 0.91 nM. Finally, the dual-mode nanoprobes performed satisfactory TP fluorescence imaging (330.0 µm penetration depth) and FLIM (τave = 50.0 ns) of endogenous miR-21 in living cells and tissues. The dual-mode platforms have promising applications in miRNA-based early detection and therapy and hold much promise for improving clinical efficacy.
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As cancer markers, hydrogen peroxide (H2 O2 ) and viscosity play an essential role in the development of tumors. Meanwhile, based on the performance of near-infrared (NIR) fluorescence imaging and the high efficiency of photodynamic therapy (PDT) and photothermal therapy (PTT) synergistic therapy, it is urgent to develop a dual-key (H2 O2 and viscosity) activated fluorescence probe for cancer phototherapy. Herein, a NIR-I/II fluorescence probe named BX-B is reported. In the presence of both H2 O2 and viscosity, the fluorescence signal of NIR-I (810 nm) and NIR-II (945 nm) can be released. In the presence of H2 O2 , the PDT and PTT effects are observed. BX-B is used to monitor its therapeutic effects in cancer cells and tumor-bearing mice due to the increased viscosity caused by PDT and PTT. In addition, the tumors of mice treated with BX-B are almost completely ablated after the laser irradiation based on its PDT and PTT synergistic therapy. This work provides a reliable platform for effective cancer treatment and immediate evaluation of therapeutic effects.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Animales , Ratones , Terapia Fototérmica , Fluorescencia , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Fototerapia , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacologíaRESUMEN
Cysteine (Cys) is a crucial biological thiol that has a vital function in preserving redox homeostasis in organisms. Studies have shown that Cys is closely related to the development of cancer. Thus, it is necessary to design an efficient method to detect Cys for an effective cancer diagnosis. In this work, a novel tumor-targeting probe (Bio-Cy-S) for dual-modal (NIR fluorescence and photoacoustic) Cys detection is designed. The probe exhibits high selectivity and sensitivity toward Cys. After reaction with Cys, both NIR fluorescence and photoacoustic signals are activated. Bio-Cy-S has been applied for the dual-modal detection of Cys levels in living cells, and it can be used to distinguish normal cells from cancer cells by different Cys levels. In addition, the probe is capable of facilitating dual-modal imaging for monitoring changes in Cys levels in tumor-bearing mice. More importantly, the excellent tumor-targeting ability of the probe greatly improves the signal-to-noise ratio of imaging. To the best of our knowledge, this is the first Cys probe to combine targeting and dual-modal imaging performance for cancer diagnosis.
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Cisteína , Colorantes Fluorescentes , Humanos , Ratones , Animales , Línea Celular Tumoral , Células HeLa , Imagen Óptica/métodosRESUMEN
Cancer is one of the major diseases that seriously endanger the health of all mankind. Accurate diagnosis of early cancer is the most promising way to reduce cancer harm and improve patient survival. However, many developed fluorescent probes for cancer imaging only have the function of identifying one marker, which cannot meet the needs of accurate diagnosis. Here, a fluorescent nanoprobe (CPH@ZIF-90) utilizing ZIF-90 to encapsulate SO2-sensitive dye (CPH) is synthesized for the sequential detection of ATP and SO2. The nanoprobe first interacts with ATP to release CPH, thus increasing the fluorescence at 685 nm and realizing the near-infrared (NIR) fluorescence detection of ATP. Then, SO2 acts on the released CPH through nucleophilic addition, affecting the π-conjugated structure of CPH and resulting in enhanced fluorescence at 580 nm. CPH@ZIF-90 exhibits satisfactory sensitivity and selectivity for sequential detection of ATP and SO2. Excitedly, CPH@ZIF-90 can sequentially image the endogenous ATP and SO2 in cells, showing sensitive fluorescence changes in dual channels (red and green). Due to the NIR emission properties of CPH@ZIF-90 and its ability to enrich in tumor, it is applied to monitor ATP and SO2 in mice and distinguish normal mice from tumor mice. The ability of CPH@ZIF-90 to sequentially detect two cancer-related biomarkers makes it provide meaningful assistance in accurate early diagnosis of cancer.
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Neoplasias , Dióxido de Azufre , Animales , Ratones , Adenosina Trifosfato , Colorantes Fluorescentes/química , Diagnóstico por Imagen , Neoplasias/diagnóstico por imagenRESUMEN
A near-infrared fluorescent probe (IC-V) for detecting viscosity is constructed. The probe has a large Stokes shift (170 nm) and an about 180-fold increase in fluorescence intensity at 700 nm. In addition, IC-V can not only distinguish cancer cells from normal cells, but also monitor viscosity in normal mice and tumor-bearing mice.
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Colorantes Fluorescentes , Neoplasias , Animales , Ratones , Humanos , Viscosidad , Neoplasias/diagnóstico por imagen , Microscopía Fluorescente/métodos , Imagen Óptica , Células HeLaRESUMEN
Herein, we report a novel visible light-induced photocatalytic system that enables intramolecular hydroarylation of unactivated alkenes. Thiosulfonate compounds were found to be the key radical precursor that mediates the Minisci-type intramolecular cyclization reaction. Under the optimal reaction conditions, a wide range of pyridyquinazolinone and pyrroloquinazolinone products were obtained in moderate to good yields.
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Viscosity is an important component of cell microenvironment, and abnormal mitochondrial viscosity is associated with many diseases such as tumor and fatty liver. Herein, a near-infrared fluorescence probe (QX-V) based on quinoline-xanthene dye for detecting viscosity is constructed. In high viscosity medium, the free rotation of single bond is inhibited and the fluorescence is released. The probe shows high sensitivity together with good selectivity. Notably, QX-V has a long excitation wavelength (710 nm) and emission wavelength (786 nm). At the same time, the probe is a positively charged molecule that can target mitochondria. QX-V can not only distinguish cancer cells from normal cells, but also make a distinction between normal cells and fatty hepatocytes. In addition, QX-V is used to image viscosity abnormality in tumor-bearing mice. The probe also has a good ability to image viscosity abnormality caused by liver injury in fatty-liver mice.
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Hígado Graso , Neoplasias , Humanos , Ratones , Animales , Colorantes Fluorescentes/química , Viscosidad , Imagen Óptica/métodos , Mitocondrias/química , Células HeLa , Hígado Graso/patología , Neoplasias/diagnóstico por imagen , Neoplasias/patologíaRESUMEN
Adenosine triphosphate (ATP), as an indispensable biomolecule, is the main energy source of cells and is used as a marker for diseases such as cancer and fatty liver. It is of great significance to design a near-infrared fluorescent nanoprobe with excellent performance and apply it to various disease models. Here, a near-infrared fluorescent nanoprobe (ZIF-90@SiR) based on a zeolitic imidazole framework is proposed. The fluorescent nanoprobes are synthesized by encapsulating the dye (SiR) into the framework of ZIF-90. Upon the addition of ATP, the structure of the ZIF-90@SiR nanoprobe is disrupted and SiR is released to generate near-infrared fluorescence at 670 nm. In the process of ATP detection, ZIF-90@SiR shows high sensitivity and good selectivity. Moreover, the ZIF-90@SiR nanoprobe has good biocompatibility due to its low toxicity to cells. It is used for fluorescence imaging of ATP in living cells and thus distinguishing normal cells and cancer cells, as well as distinguishing fatty liver cells. Due to excellent near-infrared fluorescence properties, the ZIF-90@SiR nanoprobe can not only distinguish normal mice and tumor mice but also differentiate normal mice and fatty liver mice for the first time.
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Cancer is one of the biggest public enemies of global health with its high morbidity and mortality. Achieving early diagnosis is the most effective means of reducing cancer harm, which requires the use of powerful tools to accurately identify biomarkers. However, most of the reported fluorescent probes for cancer diagnosis can only detect one substance, which makes it difficult to meet the requirements of high accuracy. Here, a fluorescent nanoprobe (CPQ@ZIF-90) for sequential detection of ATP and ONOO- is constructed by encapsulating the ONOO- sensitive unit CPQ within ZIF-90. CPQ@ZIF-90 first reacts with ATP to release CPQ, which greatly enhances the fluorescence at 740 nm. Then, the released CPQ continues to react with ONOO- and is oxidatively cleaved by ONOO- to form a coumarin product with a small π-conjugated structure, which significantly enhances the fluorescence at 510 nm. CPQ@ZIF-90 shows high sensitivity and selectivity for the detection of ATP and then ONOO-. Moreover, CPQ@ZIF-90 has good biocompatibility and successfully realizes the sequential detection of a dual-channel fluorescence change of ATP and ONOO- in living cells and zebrafish and accurately distinguishes normal cells from cancer cells. CPQ@ZIF-90 is expected to be a potential tool for accurate cancer diagnosis through sequential detection of two cancer markers.
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Neoplasias , Ácido Peroxinitroso , Adenosina Trifosfato , Animales , Biomarcadores , Cumarinas , Colorantes Fluorescentes/química , Neoplasias/diagnóstico por imagen , Ácido Peroxinitroso/química , Pez CebraRESUMEN
Viscosity is an essential microenvironmental parameter, which is related to various diseases such as acute inflammation. So it is necessary to develop a probe to monitor viscosity changes during the inflammatory progression in vivo. Herein, a HPQ (2-(2'-hydroxyphenyl)-4(3H)-quinazolinone)-based fluorescent probe named HPQ-BI-V is prepared for detecting viscosity in biological systems. The introduction of benzindole groups extends the π conjugation of HPQ, resulting in far-red emission wavelength at 610 nm. When the viscosity raises from 3.11 cP to 567.1 cP, the fluorescence signal increases 711 times, indicating the high sensitivity of the probe. Furthermore, this probe displays excellent selectivity for viscosity in comparison with other interfering analytes. Furthermore, the probe has excellent photostability and outstanding response capability in the physiological pH range. Given these advantages, HPQ-BI-V can be applied for detecting viscosity changes in HepG2 cells and zebrafish. In particular, the probe can successfully visualize viscosity changes in acute inflammatory mice induced by LPS and the assessment of anti-inflammatory drug.
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Colorantes Fluorescentes , Pez Cebra , Animales , Modelos Animales de Enfermedad , Células HeLa , Humanos , Inflamación/inducido químicamente , Ratones , Mitocondrias , ViscosidadRESUMEN
The concentration of tumor biomarker Mucin 1 (MUC 1) is highly related with many diseases, which can be employed for the early diagnosis of cancer. In this paper, an electrochemical ratiometric aptasensor with intrinsic self-calibration property for the detection of MUC 1 is presented. In this paper, Co-MOFs themselves were employed as signal substances. This strategy was fabricated by using gold nanoparticles@black phosphorus (BP) as the substrate on the electrode, followed by modification of DNA nanotetrahedrons (DTN) via Au-S bond. The terminal of DTN contains MUC 1 aptamer. In the presence of MUC 1, the signal of DNA-labeled Co-MOFs can be detected. The current signal of Co-MOFs increased and that of thionine (as reference) was unchanged upon the addition of MUC 1. Thus, an intrinsic self-calibration aptasensor was achieved. In order to simplify the modification procedure, the electrolyte solution thionine was employed as an inner reference probe. Moreover, coupling of the hybridization chain reaction (HCR) with these MOFs signal tags presents an enzyme-free method for signal amplification, endowing the proposed ratiometric biosensor detection with high reproducibility and high sensitivity. The current ratio (IIR/ISP) remained stable over 30 individual measurements performed on ten different working electrodes. Even ten repeated scans performed on a single electrode exhibited a constant current ratio. The electrochemical ratiometric aptasensor is highly sensitivity for MUC 1 with the detection limit of 1.34 fM. Our proposed ratiometric sensor has great potential for the detection of cancer-related biomarkers.