De Novo Design of a Highly Stable Ratiometric Probe for Long-Term Continuous Imaging of Endogenous HClO Burst.

Long-term continuous imaging of endogenous HClO burst is of great importance for the elucidation of various physiological or pathological processes. However, most of the currently reported HClO probes have failed to achieve this goal due to their insufficient photobleaching resistance under a laser source. Herein, a highly stable ratiometric probe, HFTC-HClO 1, which is capable of continuously monitoring endogenous HClO burst over a long period of time, has been judiciously developed. Briefly, the de novo development of HFTC-HClO 1 mainly involved three main steps: (1) novel coumarins (HFTC 1-5) were designed and synthesized; (2) the most stable scaffold, HFTC 3, was selected through dye screening and cell imaging validation; and (3) based on HFTC 3, three candidate HClO probes were constructed, and HFTC-HClO 1 was finally selected due to its superior sensing properties toward HClO. Furthermore, HFTC-HClO 1 can quantitatively measure HClO levels in various real samples with excellent recovery (>90.4%), and the use of HFTC-HClO 1-coated test strips for qualitative analysis of HClO in real samples was also achieved. In addition, the application of HFTC-HClO 1 for long-term continuous monitoring of intracellular HClO burst was successfully demonstrated. Significantly, HFTC-HClO 1 was able to visualize HClO generated in the rheumatoid arthritis mouse model.

Theranostic Fluorescent Probes.

The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.

Intramolecular cascade reaction sensing platform for rapid, specific and ultrasensitive detection of nitrite.

Nitrite is a carcinogenic substance in food. Excessive consumption of nitrite severely endangers human health. However, rapid and accurate quantification of nitrite by a simple tool is still very challenging. In this work, we designed a practical sensing platform based on 8-(o-phenylenediamine)-boron dipyrromethene (BDP-OPD) to determine nitrite in food. BDP-OPD can take a specific diazotization-cyclization cascade reaction with nitrite to form boron dipyrromethene (BODIPY), giving rise to a remarkable chromogenic reaction along with high contrast fluorescence turn-on response towards nitrite. BDP-OPD has high sensitivity, rapid response, and good selectivity. Furthermore, a portable smartphone-based fluorescence device integrated with a self-programmed Python program was fabricated, which has been successfully used to determine nitrite in food with the advantages of rapid response, low cost, ease of operation, portability, and satisfactory recoveries (92-112%). The good sensing performance rendered BDP-OPD a promising fluorescence platform for on-site visual detection of nitrite.

Endogenous CO imaging in bacterial pneumonia with a NIR fluorescent probe.

Bacterial pneumonia is a serious respiratory illness that poses a great threat to human life. Rapid and precise diagnosis of bacterial pneumonia is crucial for symptomatic clinical treatment. Endogenous carbon monoxide (CO) is regarded as a significant indicator of bacterial pneumonia; herein, we developed a near-infrared (NIR) probe for fluorescence and photoacoustic (PA) dual-mode imaging of endogenous CO in bacterial pneumonia. NO2-BODIPY could rapidly and specifically react with CO to produce strong NIR fluorescence as well as ratiometric PA signals. NO2-BODIPY has outstanding features including fast response, fluorescence/PA dual mode signals, good specificity, and a low limit of detection (LOD = 20.3 nM), which enables it to image endogenous CO in cells and bacterial pneumonia mice with high sensitivity and high contrast ratio. In particular, NO2-BODIPY has two-photon excited (1340 nm, σ1 = 1671 GM) NIR fluorescence and has been utilized to image endogenous CO in bacterial pneumonia mice with deep tissue penetration. NO2-BODIPY has been demonstrated a good capability of fluorescence/PA dual-mode imaging of CO in bacterial pneumonia mice, providing a precise manner to diagnose bacterial pneumonia.

A practical chromogenic and fluorogenic dual-mode sensing platform for rapid quantification of sulfite in food.

Sulfur dioxide (SO2) and its derivatives (HSO3- and SO32-) are widely used in food-processing. Whereas excessive consumption of sulfur dioxide and its derivatives (>0.70 mg·kg-1day-1) severely endangers human health. In this work, we rationally constructed a practical dual-mode probe (dicyanomethylene)-1-methyl-1,4-dihydroquinolin-2-yl)vinyl)-1-methylquinolinium (QMN), which underwent a specific 1, 4-Michael addition with sulfite to afford a noticeable color change from pale yellow to red along with a high-contrast fluorescence turn-on response at 598 nm. QMN has the advantages of rapid response, high signal-to-noise ratio, excellent selectivity, good water-solubility, large Stokes shift and low detection limit (LOD = 31.9 nM). QMN has been successfully used to on-site visually determine sulfite in a diversity of foods with satisfactory recoveries (91.33-111.33 %) and high accuracy (93.74-98.71 %). Furthermore, a portable smartphone-based fluorescence sensing platform was fabricated for on-site determination of sulfite in food with good performance.

Engineered Collaborative Size Regulation and Shape Engineering of Tremella-Like Au-MnOx for Highly Sensitive Bimodal-Type Lateral Flow Immunoassays.

Engineered collaborative size regulation and shape engineering of multi-functional nanomaterials (NPs) offer extraordinary opportunities for improving the analysis performance. It is anticipated to address the difficulty in distinguishing color changes caused by subtle variations in target concentrations, thereby facilitating the highly sensitive analysis of lateral flow immunoassays (LFIAs). Herein, tremella-like gold-manganese oxide (Au-MnOx ) nanoparticles with precise MnCl2 regulation are synthesized as immuno signal tracers via a facile one-step redox reaction in alkaline condition at ambient temperature. Avail of the tunable elemental composition and anisotropy in morphology, black-colored tremella-like Au-MnOx exhibits superb colorimetric signal brightness, enhanced antibody coupling efficiency, marvelous photothermal performance, and unrestricted immunological recognition affinity, all of which facilitate highly sensitive multi-signal transduction patterns. In conjunction with the handheld thermal reader device, a bimodal-type LFIA that combines size-regulation- and shape-engineering-mediated colorimetric-photothermal dual-response assay (coined as the SSCPD assay) with a limit of detection of 0.012 ng mL-1 for ractopamine (RAC) monitoring is achieved by integrating Au-MnOx with the competitive-type immunoreaction. This work illustrates the effectiveness of this strategy for establishing high-performance sensing, and the SSCPD assay may be extended to a wide spectrum of future point-of-care (POC) diagnostic applications.

Molecular engineering of fluorescence probe for real-time non-destructive visual screening of meat freshness.

Spoiled meat poses a great challenge to food security and human health, which should be addressed by the early monitoring and warning of the meat freshness. We herein exploited a molecular engineering strategy to construct a set of fluorescence probes (PTPY, PTAC, and PTCN) with phenothiazine as fluorophore and cyanovinyl as recognition site for the facile and efficient monitoring of meat freshness. These probes produce an obvious fluorescence color transition from dark red to bright cyan in response to cadaverine (Cad) through the nucleophilic addition/elimination reaction. The sensing performances were elaborately improved to achieve quick response (16 s), low detection limit (LOD = 3.9 nM), and high contrast fluorescence color change by enhancing the electron-withdrawing strength of cyanovinyl moiety. Furthermore, PTCN test strips were fabricated for portable and naked-eye detection of Cad vapor with fluorescence color change from crimson to cyan, and accurate determination of Cad vapor level with RGB color (red, green, blue) mode analysis. The test strips were employed to detect the freshness of real beef samples, and demonstrated a good capability of non-destructive, non-contact and visual screening meat freshness on site.

A colorimetric and fluorescent sensor for non-destructive screening of the freshness of shrimp and fish.

The freshness of fish and shrimp is closely associated with food safety, hence it is a wide concern to develop a facile and effective method for fast, non-destructive and visual screening the freshness of fish and shrimp. Herein, we developed a chromogenic and fluorogenic sensor (RFCC) based on resorufin for sensing of biogenic amines including cadaverine and putrescine. RFCC underwent aminolysis with cadaverine or putrescine, displaying a remarkable fluorescence turn on response at 593 nm along with obvious color change from colorless to pink. RFCC was fabricated into test strips to sense cadaverine vapor, and the RGB value of test strips showed a good linear relationship with the concentration of cadaverine (0.5 - 8.2 × 103 ppm). The RFCC tag was used to in situ screen the freshness of fish and shrimp according to obvious fluorescence change, and satisfactory results were achieved. Furthermore, this test strip was validated by total volatile base nitrogen (TVBN), providing a simple, low cost and portable tool to screen the freshness of fish and shrimp for consumers and suppliers without expensive instrumentation.

A resorufin-based fluorescence probe for visualizing biogenic amines in cells and zebrafish.

Biogenic amines (BAs) are a family of nitrogen-bearing natural organic molecules with at least one primary amine, which play an important role in living organisms. Elevated concentration of BAs may cause neuron disorder, Parkinson's disease and many other diseases. Therefore, it is essential to monitor BAs in living organisms. Herein, we reported a resorufin-based fluorescence probe for sensing of various BAs. Upon nucleophilic substitution reaction with BAs, the probe released resorufin, affording to strong fluorescence emission at 592 nm with rapid response (<8 min), good selectivity and a low detection limit (LOD = 0.47 µM). The probe has low cytotoxicity and good membrane permeability, and has been successfully used to visualize BAs in living cells and zebrafish with good performance.

Real-Time Fluorescence Screening Platform for Meat Freshness.

Meat's freshness is closely related to food safety and human health and has received increasing attention nowadays. To on-site visually screen meat freshness in a fast and non-destructive manner, we rationally constructed a series of fluorescent probes (JDCN, JDNS, and JDPY) with distinct electron-withdrawing substitution groups based on julolidine-fused coumarin. These probes underwent an aza-Michael addition followed by an elimination reaction with cadaverine to generate a colorimetric and ratiometric fluorescence response, and their sensing performance was rationally enhanced by improving the electron-withdrawing strength of substitution groups. Particularly, JDCN with a dicyanovinyl group as the reaction site exhibited outstanding sensing performance including rapid response (∼60 s), high selectivity, and low detection limit (14 nM). Furthermore, JDCN was fabricated into test kits to detect cadaverine vapor with a high-contrast fluorescence change from red to green. Based on two-color visualization of cadaverine vapor, on-site non-contact and non-destructive monitoring of meat freshness was successfully achieved. The good sensing performance rendered JDCN test kits a promising real-time fluorescence screening platform for rapid, non-destructive, and accurate evaluation of meat freshness.

Early diagnostic imaging of pneumonia with an ultra-sensitive two-photon near-infrared fluorescent probe.

The mortality rate of pneumonia increases significantly with the prolongation of illness. In the pursuit of a tool to accurately diagnose pneumonia in its early stages, we designed and synthesized a two-photon near-infrared fluorescent probe (DCQN) to identify increased concentrations of the inflammation marker SO2. The probe was found to specifically react with SO2 by undergoing a 1,4-addition reaction to generate near-infrared fluorescence with good sensitivity (6 s), a large Stokes shift (110 nm) and low detection limit (1.49 nM). DCQN has near-infrared emission as well as good two-photon performance, which can image exogenous and endogenous SO2 in cells and avoid interference from background fluorescence from cells. Furthermore, this study achieved accurate imaging of a pneumonia lesion site in deep tissues to provide a tool for the fluorescence diagnostic imaging of pneumonia in situ.

A smartphone-adaptable chromogenic and fluorogenic sensor for rapid visual detection of toxic hydrazine in the environment.

Hydrazine is an essential chemical in industries, but its high toxicity poses great threats to human health and environmental safety. Hence, it is of great significance to monitor the hydrazine in environment. In this work, we presented a chromogenic and fluorogenic dual-mode sensor RA for the detection of hydrazine based on nucleophilic substitution reaction. A linear relationship was obtained between the fluorescence intensity and the concentrations of N2H4 ranging from 0 to 35 µM (R2 = 0.9936). The sensor can determine hydrazine with fast response (within 12 min), low limit of detection (0.129 µM) and high selectivity. RA was successfully used to detect N2H4 in real water samples with good recoveries and the results corresponded to the standard method. Furthermore, the sensor-coated portable test papers were fabricated, which can visually quantify hydrazine solutions with obvious fluorescence transformation from colorless to red. Moreover, RA-loaded papers were used to create a smartphone-adaptable RGB values analytical method for quantitative N2H4 detection.

A molecular recognition platform for the simultaneous sensing of diverse chemical weapons.

Chemical warfare agents (CWAs) such as phosgene and nerve agents pose serious threats to our lives and public security, but no tools can simultaneously screen multiple CWAs in seconds. Here, we rationally designed a robust sensing platform based on 8-cyclohexanyldiamino-BODIPY (BODIPY-DCH) to monitor diverse CWAs in different emission channels. Trans-cyclohexanyldiamine as the reactive site provides optimal geometry and high reactivity, allowing trans-BODIPY-DCH to detect CWAs with a quick response and high sensitivity, while cis-BODIPY-DCH has much weaker reactivity to CWAs due to intramolecular H-bonding. Upon reaction with phosgene, trans-BODIPY-DCH was rapidly converted to imidazolone BODIPY (<3 s), triggering green fluorescence with good sensitivity (LOD = 0.52 nM). trans-BODIPY-DCH coupled with nerve agent mimics, affording a blue fluorescent 8-amino-BODIPY tautomer. Furthermore, a portable test kit using trans-BODIPY-DCH displayed an instant response and low detection limits for multiple CWAs. This platform enables rapid and highly sensitive visual screening of various CWAs.

Fast visual monitoring of the freshness of beef using a smart fluorescent sensor.

Spoiled meat contains many pathogenic bacteria; hence, the intake of spoiled food can lead to various illnesses. To screen the freshness of food, in this study, we devised a ratiometric fluorescence sensor dicyanovinyl coumarin (CMDC) for the determination of cadaverine, an important biomarker for the spoilage of meat. CMDC underwent aza-Michael addition with cadaverine, exhibiting high sensitivity, fast response (50 s), and distinct fluorescence color transition. Test strips fabricated using CMDC showed a noticeable color change from red to green when exposed to cadaverine vapor. The test strips were successfully used to visually monitor the spoilage of beef based on the fluorescence color change. Furthermore, the as-developed test strip coupled with a smartphone provides a simple tool for consumers and suppliers to obtain information about meat quality.

Recyclable europium functionalized metal-organic fluorescent probe for detection of tryptophan in biological fluids and food products.

An europium functionalized metal-organic fluorescent probe, Eu3+@UiO-66-FDC was constructed by post-synthetic modification through coordination interactions. Eu3+@UiO-66-FDC displayed high selectivity and sensitivity toward Tryptophan (Trp) among all the 20 natural amino acids and other general compounds in food and biological samples, with a wide linear concentration range (0-1000 µM), low detection limit (0.29 µM), and a rapid response (<1 min). Besides, this probe was utilized to detect Trp in rabbit blood serum and milk samples with good recoveries, which were verified by high-performance liquid chromatography (HPLC). Notably, this fluorescent probe proved to be a recyclable material. Hence, this work provides a reliable and recyclable fluorescent probe applicable toward the detection of Trp in biological fluids and/or food products.

Highly selective detection of Cu2+ in aqueous media based on Tb3+-functionalized metal-organic framework.

In this work, a metal-organic framework UiO-66-(COOH)2 has been synthesized and is further functionalized with Tb3+ through coordination interactions. The functionalized MOF, denoted as Tb3+@UiO-66-(COOH)2, is fully characterized and further developed as an excellent fluorescent probe to monitor Cu2+ ions in aqueous media by fluorescence quenching effect. Tb3+@UiO-66-(COOH)2 exhibits high selectivity and sensitivity, broad linear concentration range (0-200 µM), low detection limits (0.23 µM), fast response speed (within 1 min), as well as in situ naked eye observation under UV light for sensing Cu2+ ion. Furthermore, this probe was successfully employed to detect Cu2+ ion in real water with good recovery. Hence, this work developed a very excellent fluorescent sensor with high potential practical applications for detection of Cu2+ ion in environmental water samples.

A novel cross-linked nanoparticle with aggregation-induced emission properties for cancer cell imaging.

Fluorescent probes have been widely used in bioimaging as an efficient and convenient analytical tool. From the initial inorganic nanoparticles and small organic molecules to polymeric nanoparticles, scientific researchers have been trying to develop a probe with strong fluorescence and excellent biocompatibility. In this study, a tetraphenylethylene derivative with AIE properties and hyaluronic acid modified by methacrylic anhydride were combined to prepare a novel nanoparticle (HA-Ac-Pha-C) as a fluorescent probe by a photochemical cross-linking reaction. The fluorescence intensity and size of the nanoparticles were characterized by different techniques. It was confirmed that cross-linked nanoparticles not only showed stronger fluorescence, but also had better photostability while still maintaining 85.9% of the initial intensity after seven days. Moreover, cells and zebrafish imaging experiments also demonstrated that nanoparticles show specific fluorescence labeling for cancer cells and excellent biocompatibility in living organisms.

A distinctive mitochondrion-targeting, in situ-activatable near-infrared fluorescent probe for visualizing sulfur dioxide derivatives and their fluctuations in vivo.

Sulfur dioxide derivatives are intimately involved in some physiological processes in organisms, and high levels of these substances can cause many diseases. Herein, we rationally prepared a mitochondrion-targeting, in situ-activatable near-infrared (NIR) fluorescent probe (DCQN) by coupling 2-(3,5,5-trimethylcyclohex-2-enylidene)malononitrile with 3-quinolinium carboxaldehyde. DCQN displayed a NIR fluorescence turn-on signal to indicate the presence of HSO3-, along with a considerable hyperchromic shift from light yellow to purple via a 1,4-nucleophilic addition reaction. We were able to use DCQN to instantaneously and quantitatively determine the concentration of HSO3- with high specificity, a low detection limit (24 nM), a large Stokes shift (∼110 nm), and a high contrast ratio. Moreover, DCQN displayed good mitochondrion-targeting abilities and was in situ-activated by HSO3- to produce NIR fluorescence for imaging HSO3- in the mitochondria of live breast cancer cells. Furthermore, DCQN was used to monitor HSO3- in zebrafish with a high contrast ratio.

Hyaluronic Acid-Modified Fluorescent Probe for Dual Color Imaging of Living Cell.

Nanoprobes with biocompatibility and strong fluorescence have unique advantages in tumor detection and diagnosis. A nanoparticle with dual fluorescent signals for detecting and imaging of tumor cells was prepared, in which the outer layer of the particle is a hyaluronic acid-modified molecule with aggregation-induced emission properties, and the inner content is the boron-dipyrromethene (BODIPY) derivative. This nanoparticle has low critical micelle concentration, small size, and high fluorescence intensity. Cell imaging experiments showed that it is capable of stable cell imaging with a red and blue fluorescence conversion in response to cancer cells. Furthermore, the zebrafish experiment confirmed that it can be used for biological imaging. Nanoparticles with dual fluorescence response properties of the coated structure provide an effective way for detecting cancer cells.

A paper-based chemosensor for highly specific, ultrasensitive, and instantaneous visual detection of toxic phosgene.

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.