RESUMEN
Heightened oxidative stress is the principal driver behind the altered metabolism of neurotransmitters within the brains of Parkinson's disease (PD). Hypochlorous acid (HClO), a variant of reactive oxygen species (ROS), plays a crucial role in several lysosomal activities. An irregular concentration of HClO may result in significant molecular damage and contribute to the onset of neurodegenerative disorders. Despite this, the precise role of lysosomal HClO in PD remains unclear, due to its fast reactivity and low levels. This is further complicated by the lack of effective in situ imaging techniques for accurately tracking its dynamics. Therefore, it is of great significance to use effective tools to map the lysosomal HClO during the pathological process of PD. In this study, we propose a fluorogenic probe named Lys-PTZ-HClO for the specific and sensitive detection of HClO. Lys-PTZ-HClO exhibits features like a fast response time (10 s) and a low detection limit (0.72 µM). Benefiting from its superior properties, the probe was used to visualize the basal HClO levels, and the variation of HClO levels in lysosomal of living cells. More importantly, this probe was successfully applied for the first time to reveal increased lysosomal HClO in a cellular model of PD.
Asunto(s)
Colorantes Fluorescentes , Ácido Hipocloroso , Lisosomas , Enfermedad de Parkinson , Ácido Hipocloroso/análisis , Ácido Hipocloroso/metabolismo , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Lisosomas/química , Lisosomas/metabolismo , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Imagen ÓpticaRESUMEN
Diabetes, as a metabolic disorder, has been implicated in organ dysfunction, often correlated with aberrant changes in viscosity. Lysosomal viscosity serves as an indicator of the lysosome's condition and activity, as it always varies synchronously with the change of lysosome's positioning, structure, and internal constituents. Diabetes, a condition within the metabolic disease category, has the potential to disrupt organ function due to irregular changes in viscosity. Therefore, early and precise diagnosis of diabetes is crucial for the prevention and management of diabetic conditions. Understanding the correlation between viscosity variations and lysosomal changes in vivo is vitally important for researching associated diseases. In this study, we developed Lyso-V, a near-infrared (NIR) fluorescent probe targeting lysosomes, with ultrasensitivity to viscosity changes. This probe, designed with a donor-π-bridge-acceptor (D-π-A) structure, exhibits a significant increase in NIR fluorescence intensity (approximately 690 times) when responding to viscosity, due to a twisted intramolecular charge transfer (TICT) mechanism. Furthermore, the probe designed specifically for lysosomes, enables the detection of changes in lysosomal viscosity as well as autophagy processes. Notably, through the application of this probe, we have detected an increased viscosity within the pathological model of the diabetic mouse. Moreover, Lyso-V was employed to measure the viscosity in diabetic mice. Owing to the multifaceted nature of the Lyso-V probe, it is anticipated to act as a practical and potent resource for deepening our understanding of the pathophysiological aspects of diabetes and aiding in its early detection.
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Diabetes Mellitus Experimental , Colorantes Fluorescentes , Lisosomas , Lisosomas/química , Lisosomas/metabolismo , Animales , Colorantes Fluorescentes/química , Viscosidad , Ratones , Humanos , Masculino , Rayos Infrarrojos , Imagen ÓpticaRESUMEN
Dipeptidyl peptidase 4 (DPP4) plays a key role in glucose metabolism, which has been a close target for diabetes pathology and treatment. It is significant for the evaluation of cellular DPP4 activity in various biological systems. Fluorescence imaging technology is currently a popular method for detecting enzymes in living cells due to its advantages of high selectivity, high sensitivity, high spatiotemporal resolution, and real-time visualization. Herein, a near-infrared (NIR)-emissive probe NEDP with a large Stokes shift (153 nm) was developed for the assay of DPP4 activity. Upon addition of DPP4, NEDP can emit a significant turn-on NIR fluorescence signal (673 nm) with high sensitivity and specificity. Moreover, NEDP can successfully be used for imaging of intracellular DPP4, confirming the regulation of DPP4 expression in hyperglucose and its treatment in living cells. Most importantly, NEDP can not only monitor the changes of DPP4 in vivo but also show that DPP4 in diabetes is mainly up-regulated in the liver, and the level of DPP4 is positively correlated with the pathological damage of the liver. In addition, NEDP can identify the serum of diabetic patients from healthy people through the fluorescence response to DPP4. These results demonstrated that the designed probe NEDP provides a prospective visual tool to explore the relationship between DPP4 and diabetes and would be applied for detecting serum of diabetes in the clinic.
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Diabetes Mellitus Experimental , Dipeptidil Peptidasa 4 , Colorantes Fluorescentes , Hígado , Dipeptidil Peptidasa 4/metabolismo , Dipeptidil Peptidasa 4/sangre , Animales , Humanos , Ratones , Hígado/metabolismo , Hígado/patología , Colorantes Fluorescentes/química , Diabetes Mellitus Experimental/metabolismo , Imagen Óptica , Rayos Infrarrojos , MasculinoRESUMEN
Carboxylesterases (CESs) are critical for metabolizing ester-containing biomolecules and are specifically important in liver metabolic disorders. The modulation of CESs is also an important issue in pharmacology and clinical applications. Herein, we present a near-infrared (NIR) CES fluorescent probe (NCES) based on the protection-deprotection of the hydroxyl group for monitoring CES levels in living systems. The NCES probe has good selectivity and sensitivity for CESs with a limit of detection (LOD) of 5.24 mU mL-1, which allows for tracing the fluctuation of cellular CES after treatment with anticancer drugs and under inflammation and apoptosis states. Furthermore, NCES can be successfully applied for guiding liver cancer surgery with high-contrast in vivo imaging and detecting clinical serum samples from liver cancer patients. This work showed that the NCES probe has great potential in drug development, imaging applications for medical diagnosis, and early-stage detection for clinical liver diseases.
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Antineoplásicos , Neoplasias Hepáticas , Humanos , Carboxilesterasa , Hidrolasas de Éster Carboxílico , Imagen Óptica/métodosRESUMEN
Diabetes and its complications, such as diabetes liver disease, is a major problem puzzling people's health. The detection of redox states in its pathological process can effectively help us gain a deeper understanding of the disease. The pair of oxidation-reduction substances peroxynitrite (ONOO- ) and glutathione (GSH) is considered to be closely related to their occurrence and development. Thus, direct visualization of ONOO- and GSH in diabetes liver disease is critical to evaluate the disease at the molecular level. Herein, two activatable agents NTCF-ONOO- and NTCF-GSH are prepared for selectively detecting ONOO- and GSH through protection and deprotection strategies based on hydroxyl and amino groups of near-infrared fluorophore. Fluorescence imaging of exogenous and endogenous ONOO- and GSH changes in living cells and in vivo is observed. The ONOO- and GSH level in the diabetes liver disease cellular model are visualized and the possible redox imbalance mechanism related to the oxidized (NAD+ ) and reduced (NADH) nicotinamide adenine dinucleotides is explored in this process. Moreover, these probes can sensitively recognize ONOO- and GSH in the process of oxidative stress resulting from streptozotocin and streptozotocin/acetaminophen-induced complex diabetic liver disease in vivo. In addition, they can be applied for monitoring the clinical serum sample related with diabetic patients.
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Diabetes Mellitus , Hepatopatías , Humanos , Ácido Peroxinitroso , Colorantes Fluorescentes/farmacología , Estreptozocina , Imagen Óptica , GlutatiónRESUMEN
Ferroptosis plays an important role in the early stage of myocardial ischemia/reperfusion (MI/R) injury, which is closely associated with the antioxidant damage of mitochondrial cysteine (Cys)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis. Visualization of Cys and GSH in mitochondria is meaningful to value ferroptosis and further contributes to understanding and preventing MI/R injury. Herein a mitochondria-targetable thiols fluorescent probe (MTTP) was designed and synthesized based on sulfonyl benzoxadiazole (SBD) chromophore with a triphenylphosphine unit as the mitochondria-targeted functional group. Cys and GSH can be differentiated by MTTP with two distinguishable emission bands (583 nm and 520 nm) through the controllable aromatic substitution-rearrangement reaction. Importantly, MTTP is capable of monitoring ferroptosis and its inhibition by measuring mitochondrial Cys and GSH. MTTP was also employed to non-invasively detect ferroptosis during oxygen and glucose deprivation/reoxygenation (OGD/R)-induced MI/R injury in H9C2 cells. In a word, MTTP provides a visual tool that can simultaneously detect Cys and GSH to monitor ferroptosis processes during MI/R injury, which helps for more deeper understanding of the role of ferroptosis in MI/R injury-related diseases.
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Ferroptosis , Daño por Reperfusión Miocárdica , Humanos , Colorantes Fluorescentes/farmacología , Cisteína , Glutatión , Mitocondrias , Compuestos de SulfhidriloRESUMEN
Hepatocellular carcinoma (HCC) is a type of cancer associated with a high rate of mortality and morbidity. In order to achieve precise HCC theranostics, it is important to develop excellent fluorescent probes. However, the existing probes are not sensitive or specific enough to accurately identify HCC margins and contours. For diagnosing HCC and identifying tumors during surgery, it is urgent to engineer highly sensitive and selective fluorescent probes. Liver tumor progression is closely associated with leucine aminopeptidase (LAP) overexpression, a biomarker of liver cancer. Herein, we have rationally designed a NIR fluorescent probe, NLAP, which is specially activated by LAP. The probe exhibited high sensitivity (detection limit = 6.8 mU L-1) and superior affinity (Km = 2.98 µM) for LAP. With this probe, we distinguished cancer cells overexpressing LAP from normal cells and applied it intraoperatively to guide liver tumor excisions. Furthermore, NLAP was employed to successfully detect the LAP of intestinal and splenic metastatic tumors in orthotopic liver tumor mice by "in situ spraying" and good performances were demonstrated.
RESUMEN
Superoxide anion (O2â¢-) is an important reactive oxygen species (ROS) and participates in various physiological and pathological processes in the organism. The O2â¢- burst induced by ischemia-reperfusion (I/R) is associated with cardiovascular disease and promotes the cell apoptosis. In this work, a turn-on type Golgi-targeting fluorescent probe Gol-Cou-O2â¢- was rationally designed for sensitive and selective detection of O2â¢-. The minimum detection limit concentration for O2â¢- was about 3.9 × 10-7 M in aqueous solution. Gol-Cou-O2â¢- showed excellent capacity of detecting exogenous and endogenous O2â¢- in living cells and zebrafish, and was also used to capture the up-regulated O2â¢- level during the duration of I/R process in cardiomyocytes. Golgi Phosphoprotein 3 (GOLPH3) is a potential Golgi stress marker protein and plays a key role in cells apoptosis during I/R. The fluorescence imaging and flow cytometry assay results indicated that silencing GOLPH3 through siRNA could give rise to the down-regulated O2â¢- level and alleviation of apoptosis in I/R myocardial cells. Thus, development of Gol-Cou-O2â¢- provides a diagnostic tool for myocardial oxidative stress injury and distinct insights on roles of GOLPH3 in myocardial I/R injury.
Asunto(s)
Daño por Reperfusión Miocárdica , Superóxidos , Animales , Colorantes Fluorescentes/toxicidad , Colorantes Fluorescentes/metabolismo , Daño por Reperfusión Miocárdica/diagnóstico por imagen , Daño por Reperfusión Miocárdica/patología , Pez Cebra , Especies Reactivas de Oxígeno/metabolismo , Oxígeno/metabolismo , Aparato de Golgi/metabolismoRESUMEN
Uranium is one of the most important radionuclides but could also cause potential health risks to human beings due to its radioactive and chemical toxicity. It is an urgent task to develop a simple but efficient sensing platform for UO22+, the main existing form of uranium in environment. Herein, a rhodamine-functionalized carbon dots (o-CDs-Rho) was synthesized and applied for UO22+ sensing through a simple but novel aggregation-enhanced FRET strategy. The weak FRET efficiency (16.2%) of o-CDs-Rho in dispersed solution is significantly enhanced (>77.2%) after UO22+ triggered aggregation due to the increased number of rhodamine acceptors around each CDs from dispersed 80 to aggregated 2800. This is the first ratiometric fluorescence sensor with an inverse change of fluorescence intensity at dual emission wavelengths under single-wavelength excitation for UO22+. Under optimized experiment conditions, o-CDs-Rho nanosensor shows a low detection limit of 53 nM and excellent selectivity. Meanwhile, the as-prepared nanosensor also shows high reliability and stability. These excellent properties make it successful in detecting uranium content in real samples.
RESUMEN
Ferrous ion (Fe2+) is a crucial metal ion in the body and participates in the diseases related to oxidation and reduction. Golgi apparatus is the main subcellular organelle of Fe2+ transport in cells, and the stability of its structure is related to the Fe2+ at an appropriate concentration. In this work, a turn-on type Golgi-targeting fluorescent chemosensor Gol-Cou-Fe2+ was rationally designed for sensitive and selective detection of Fe2+. Gol-Cou-Fe2+ showed excellent capacity of detecting exogenous and endogenous Fe2+ in HUVEC and HepG2 cells. It was used to capture the up-regulated Fe2+ level during the hypoxia. Moreover, the fluorescence of sensor was enhanced over time under Golgi stress combining with the reduce of Golgi matrix protein GM130. However, elimination of Fe2+ or addition of nitric oxide (NO) would restore the fluorescence intensity of Gol-Cou-Fe2+ and the expression of GM130 in HUVEC. Thus, development of chemosensor Gol-Cou-Fe2+ provides a new window for tracking Golgi Fe2+ and elucidating Golgi stress-related diseases.
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Colorantes Fluorescentes , Hierro , Colorantes Fluorescentes/química , Hierro/química , Aparato de Golgi/metabolismo , Fluorescencia , IonesRESUMEN
Dual-channel fluorescent probes could respond to a specific target and emit different wavelengths of fluorescence before and after the response. Such probes could alleviate the influence caused by the variation of the probe concentration, excitation intensity, and so on. However, for most dual-channel fluorescent probes, the probe and fluorophore faced spectral overlap, which reduced sensitivity and accuracy. Herein, we introduced a cysteine (Cys)-responsive and near-infrared (NIR) emissive AIEgen (named TSQC) with good biocompatibility to dual-channel monitor Cys in mitochondria and lipid droplets (LDs) during cell apoptosis through wash-free fluorescence bio-imaging. TSQC can label mitochondria with bright fluorescence around 750 nm, and after reacting with Cys, the reaction product TSQ could spontaneously target LDs with emissions around 650 nm. Such spatially separated dual-channel fluorescence responses could significantly improve detection sensitivity and accuracy. Furthermore, the Cys-triggered dual-channel fluorescence imaging in LDs and mitochondria during apoptosis induced by UV light exposure, H2O2, or LPS treatment is clearly observed for the first time. Besides, we also report here that TSQC can be used to image subcellular Cys in different cell lines by measuring the fluorescence intensities of different emission channels. In particular, TSQC shows superior utility for the in vivo imaging of apoptosis in acute and chronic epilepsy mice. In brief, the newly designed NIR AIEgen TSQC can respond to Cys and separate two fluorescence signals to mitochondria and LDs, respectively, to study Cys-related apoptosis.
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Cisteína , Epilepsia , Humanos , Ratones , Animales , Cisteína/metabolismo , Colorantes Fluorescentes/metabolismo , Peróxido de Hidrógeno/metabolismo , Gotas Lipídicas/metabolismo , Límite de Detección , Células HeLa , Epilepsia/diagnóstico por imagen , Epilepsia/metabolismo , Mitocondrias/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the liver with poor prognosis. In order to improve the prognosis and overall survival of patients with HCC, it is important to identify it at early stage and resect it precisely. Cell microenvironment, active compounds, and enzymes may change during the cancerization of hepatocytes. Hypochlorous acid (HClO), one of the most significant signal molecules in the cellular signaling pathway, plays an important role in many cellular processes. To detect and treat liver cancers, it is imperative to study how HClO levels change in hepatocytes. However, developing fluorescent probes specific to liver cells to detect HClO still challenging. Herein, we designed and synthesized a NIR hepatocyte-specific fluorescent probe (MBH-MT) that displayed excellent optical properties for detecting HClO in biological samples. Cell imaging experiment conducted with the unique probe MBH-MT, showed that the biocompatible sensor is capable of monitoring HClO and distinguishing normal cells from cancer cells (e.g., HepG2, HUVEC, RAW264.7, L02 and HK-2 cells). An organ imaging experiment with the probe MBH-MT demonstrated its effectiveness in diagnosing and imaging hepatocellular carcinoma in vivo. MBH-MT's in situ imaging also demonstrated that it can target and image mouse hepatocellular carcinomas. Furthermore, MBH-MT has also successfully been used to diagnose and guide liver cancer surgery early. In the future, we expect that this powerful tool may be help in the detection and imaging of hepatocellular carcinoma, which may affect a large number of people.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Colorantes Fluorescentes , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Imagen Óptica/métodos , Ácido Hipocloroso/metabolismo , Microambiente TumoralRESUMEN
Drug-induced acute kidney injury (DIAKI) is associated with high morbidity and mortality. It remains a diagnostic and therapeutic dilemma due to failure of providing unambiguous real-time feedback on nephrotoxicity, which is regarded as a serious problem in clinics. Herein, we report a reversible fluorescence probe, NRN, to monitor the ONOO-/GSH in an acute kidney injury model. The NRN near-infrared fluorescent probe features a big Stokes shift (83 nm), which was oxidized by ONOO- and reduced by succussive glutathione (GSH) with excellent selectivity and good sensitivity (detection limit: 418 nM and 0.28 mM, respectively). Taking the reversibility of NRN toward ONOO- and GSH, real-time evaluations in vivo with cisplatin (CP) alone and CP combined with acetaminophen-stimulated acute kidney injury and the following remedy process with l-carnitine were realized for the first time. The experiments revealed that acute kidney injury caused by combined drugs might be more serious and irreversible under certain conditions. Therefore, NRN could act as a potential tool for understanding oxidative stress-related DIAKI disease processes.
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Lesión Renal Aguda , Colorantes Fluorescentes , Humanos , Ácido Peroxinitroso , Oxidación-Reducción , Glutatión , Imagen Óptica/métodos , Estrés Oxidativo , Riñón/metabolismoRESUMEN
Conventional chemotherapy (CT) is associated with severe side effects and inducible resistance, making it difficult to meet clinical requirements, forcing the development of new multifunctional prodrugs for precision medicine. In recent decades, researchers and clinicians have focused on developing of multifunctional chemotherapeutic prodrugs with tumor-targeting capability, activatable and traceable chemotherapeutic activity, as a powerful tool to improve theranostic outcomes in cancer treatment. The conjugates of near-infrared (NIR) organic fluorophores and chemotherapy reagents create an exciting avenue for real-time monitoring of drug delivery and distribution, as well as the combination of chemotherapy and photodynamic therapy (PDT). Therefore, there are great opportunities for researchers to conceive and exploit multifunctional prodrugs that can visualize chemo-drugs release and tumor treatment inâ vivo. In this review, the design strategy and the recent progress of multifunctional organic chemotherapeutic prodrugs for activating NIR fluorescence imaging-guided therapy are described and discussed in detail. Finally, the prospects and challenges of multifunctional chemotherapeutic prodrugs for NIR fluorescence imaging-guided therapy are provided.
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Antineoplásicos , Nanopartículas , Neoplasias , Fotoquimioterapia , Profármacos , Humanos , Profármacos/farmacología , Profármacos/uso terapéutico , Sistemas de Liberación de Medicamentos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Imagen Óptica , Nanomedicina Teranóstica , Nanopartículas/uso terapéutico , Línea Celular TumoralRESUMEN
Selective fluorescence imaging of analytes is a challenge for monitoring diseases as homologues interfere with the imaging agents. Leucine aminopeptidase (LAP), a kind of protease, is related to tumor pathogenesis. The known LAP fluorescent probes based on leucine recognition have limited selectivity. Herein, a selective t-butyl-alanine recognition unit for LAP through the ligand regulation strategy is prepared as a new near-infrared (NIR) fluorescent probe (DCM-LAP) having a large Stokes shift of 214 nm and a high sensitivity with a detection limit of 168 mU/L. DCM-LAP has an enhanced response toward LAP with NIR fluorescence at 656 nm based on intramolecular charge transfer. The probe is selective without being interfered with by biological enzymes including the aminopeptidase N (APN). DCM-LAP can image LAP activity in living cells. It can also visualize the cell invasion and migration processes. DCM-LAP is employed in the real-time imaging of LAP in tumor-bearing nude mice and guides in the accurate resection of breast tumors. It also distinguishes tumor tissues from normal with a high tumor-to-normal ratio (9.8). The DCM-LAP probe can thus assist in the investigations of LAP-associated clinical disease.
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Colorantes Fluorescentes , Neoplasias , Animales , Ratones , Leucil Aminopeptidasa , Ratones Desnudos , Neoplasias/diagnóstico por imagen , Imagen ÓpticaRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory disease destroying lungs irreversibly with high mortality rates. There are challenges in diagnosing IPF and treating it at an early stage. Mounting evidence suggests that hypochlorous acid (HClO) can help in diagnosing inflammation and relevant conditions. Pulmonary fibrosis is linked to the mitochondrial oxidative stress where excessive HClO production is a key molecular mechanism. Measuring mitochondrial HClO levels assists in the investigations of how the mitochondrial oxidative stress affects IPF. Herein, NIR-PTZ-HClO was developed and optimized as a probe for detecting fluctuations in HClO concentrations of cells and mice models through near-infrared (NIR) fluorescence. The probe featured large Stokes shift of 150 nm, NIR turn-on signal at 650 nm, high sensitivity (45-fold) and quick HClO detection (2 s). The probe is selective for HClO in the presence of range of other analytes. NIR-PTZ-HClO visualized both endogenous and exogenous HClO in living cells (RAW264.7, H460 and A549). The probe monitored HClO in mice models with IPF and moreover the HClO profile could be tracked during the IPF process. The probe also detected precipitous decrease in HClO levels in IPF mice treated with OFEV. NIR-PTZ-HClO probe has thus the potential for earlier diagnosis of lung fibrosis, thereby improving the treatment efficacy.
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Colorantes Fluorescentes , Fibrosis Pulmonar Idiopática , Ratones , Animales , Ácido Hipocloroso , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Inflamación , Microscopía FluorescenteRESUMEN
γ-Glutamyltransferase (GGT) has been recognized as an important clinical biomarker that is closely related to many diseases. Visualizing the GGT fluctuation facilitates early disease-related diagnosis and therapy. Herein, an activated probe (NIR-GGT) for the imaging of GGT activity was prepared. The probe consists of a stable NIR fluorophore with the tunable amino group decorated with the γ-glutamate group as a GGT-sensing unit linked by a self-elimination group. NIR-GGT can sensitively recognize GGT and cause a strong turn-on fluorescent and photoacoustic signal. The up-regulation of the GGT expression in acetaminophen-induced acute liver injury was imaged using NIR-GGT. The probe can track changes in the GGT level in the early stages of drug-induced acute liver injury (DIALI) and its remedy process by fluorescent and photoacoustic dual-modality imaging with a high temporal-spatial resolution. NIR-GGT can also be used to differentiate between tumor and para-carcinowa tissues in vivo. The probe may be a potential tool for the diagnosis of early-stage DIALI and accurate tumor resection in the clinical field.
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CO-releasing molecule-3 (CORM-3), mainly metal carbonyl compounds, is widely used as experimental tools to deliver CO, a biological "gasotransmitter", in mammalian systems. CORM-3 is also proposed as a potential new antimicrobial agent, which kills bacteria effectively and rapidly in vitro and in animal models. Organelle-targeting therapy, as a highly effective therapeutic strategy with little toxic and side effects, has important research significance and development prospects. Therefore, the development of effective methods for detecting and tracking CORM-3 at the subcellular level has important implications. In this paper, an easily available Golgi-targetable fluorescent probe (Golgi-Nap-CORM-3) was proposed for CORM-3 detection. In the probe Golgi-Nap-CORM-3, the phenyl sulfonamide group was selected as the Golgi-targetable unit, naphthalimide dye was chosen as a fluorophore, and the nitro group was selected as a CORM-3-responsive unit. Golgi-Nap-CORM-3 shows a CORM-3-reponsive increase of fluorescence emission at 520 nm. Using the excellent probe, the change of CORM-3 in HeLa cells, HepG2 cells, and zebrafish is successfully monitored. This study demonstrates very important information for the study of CORM-3 in vivo systems.
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Liver cancer is a malignant tumor with both high morbidity and mortality. The traditional treatment method is mainly based on hepatectomy for liver tumor. However, it is difficult to accurately distinguish the tumor tissue and its boundary with the naked eye and palpation, leading to an ambiguous resection result, finally causing high recurrence of liver cancer. Molecular fluorescent probes possessing numerous advantages, such as non-invasiveness, high sensitivity, and real-time imaging, have been extensively studied in liver cancer imaging and therapy. In this review, we briefly introduce the recent developments of always-on and activatable fluorescent probes in liver cancer imaging and therapy. Future potential challenges of the fluorescent probes for liver tumor imaging are also discussed. We expect that this review would improve the fluorescent probes development for real clinical application of liver cancer disease.
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Colorantes Fluorescentes , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen Molecular , Sondas Moleculares , Imagen Óptica/métodosRESUMEN
Carbon monoxide (CO) is regarded as one of the most important gaseous transmitters, playing a vital role in biological systems; meanwhile, abnormal levels of CO can be correlated with conditions such as lung disease, Alzheimer's disease, and cardiovascular disease. CO-releasing molecules (CORMs) are chemical agents used to release CO as an endogenous, biologically active molecule in order to treat diseases. CO-releasing molecule-3 (CORM-3), as a convenient and safe CO donor and therapeutic drug molecule, has been widely used to release exogenous CO in living cells to study the physiological and pathological roles of CO in living systems. Herein, we designed a NIR-emitting probe (NIR-CORM-3) with a large Stokes shift based on a 4-(dimethylamino)cinnamaldehyde lepidine derived fluorophore. A 4-nitrobenzyl group was selected as the CORM-3 recognizing moiety, and the probe is able to selectively and sensitively respond to CORM-3 (within only 15 min). Upon encountering CORM-3, NIR-CORM-3 releases a fluorophore with a response at 670 nm, and it shows a remarkable Stokes shift (up to 250 nm). In addition, NIR-CORM-3 has low cytotoxicity and exhibits outstanding NIR imaging abilities in living cells and mice.