Rapid, portable and visualizing nitrite detection enabled by a rationally designed meso-aminoindole substituted pyronine-based fluorescent probe.

Nitrite (NO2-) widely exists in our daily diet, and its excessive consumption can lead to detrimental effects on the human central nervous system and an elevated risk of cancer. The fluorescence probe method for the determination of nitrite has developed rapidly due to its simplicity, rapidity and sensitivity. Despite establishing various nitrite sensing platforms to ensure the safety of foods and drinking water, the simultaneous achievement of rapid, specific, affordable, visualizing, and on-site nitrite detection remains challenging. Here, we designed a novel fluorescent probe by using Rhodamine 800 as the fluorescent skeleton and 5-aminoindole as the specific reaction group to solve this problem. The probe shows a maximal fluorescence emission at 602 nm, thereby avoiding background emission interference when applied to food samples. Moreover, this unique probe exhibited excellent sensing capabilities for detecting nitrite. These included: a rapid response time within 3 min, a noticeable color change that the naked eye can observe, a low detection limit of 13.8 nM, and a remarkable selectivity and specificity to nitrite. Besides that, the probe can detect nitrite quantitatively in barreled drinking water, ham sausage, and pickles samples, with good recoveries ranging from 89.0 % to 105.8 %. More importantly, based on the probe fixation and signal processing technology, a portable and smart sensing platform was fabricated and made convenient and rapid analysis the content of NO2- in real samples possible. The results obtained in this work provide a new strategy for the design of high-performance nitrite probes and feasible technology for portable, rapid and visual detection of nitrite, and this probe holds the potential as a practical tool for alleviating concern regarding nitrite levels.

Rapid quantitative evaluation of total polar materials (TPM) in frying oil based on an "off-on" fluorescence viscosity response probe.

The content of total polar material (TPM) is considered as a comprehensive indicator to evaluate the quality of edible oils which should be discarded and no longer be used when TPM content exceeding 27 %. Nevertheless, there is currently a lack of a convenient and efficient TPM detection method, which is a meaningful challenge. With the increase of TPM content, the viscosity of frying oil grows, and the two maintain a satisfactory positive correlation. Consequently, an "off-on" fluorescence probe TCF-PR method based on viscosity-response has been developed. There exists a good linear relationship between the fluorescence intensity of the probe and the TPM content of soybean oil ((R2 = 0.9936) and salad oil (R2 = 0.9878), accompanying with the advantage of fast response (3 s), which means the rapid detection of TPM can be realized to determine the quality of frying oil in the field of food safety.

A novel amidine-based fluorescent probe TPE-4+ for rapid detection of anionic surfactant sodium dodecyl sulfate.

An accurate, fast, and simple surfactant detection method is of great significance for monitoring surfactants pollution. Sodium dodecyl sulfate (SDS) is one of the most commonly used anionic surfactants and has been listed as an important monitoring pollutant for surfactant residues. Herein, a novel fluorescent probe named TPE-4+ with four amidines as the recognition functional group and tetraphenylethene as the fluorophore was fabricated. Due to the special intramolecular environment, the probe showed selectively identification towards SDS which made an aggregation induced fluorescence enhencement. Under the optimum conditions, the fluorescence enhencement of TPE-4+ is linearly related to the concentration of SDS in the range of 5.0-60.0 µM with limit of detection (LOD) of 0.010 µM and limit of quantification (LOQ) of 0.034 µM. Relative to the reported methods, the probe in our work showed better selectivity and sensitivity. The proposed method was successfully applied for the SDS determination of disinfecting bowls.

A highly water-soluble hydrogen-bond-induced emission carbon dots for ratiometric fluorescent detection of water content in organic solvents.

Water in organic solvents is a prevalent impurity that significantly influences chemical reactions and industrial processes. Carbon dots (CDs) gained attention as promising tools for chemosensing due to their advantageous characteristics, including easy synthesis, cost-effectiveness, and excellent adjustability and stability. However, limited solubility in water and turn off fluorescence response mode hinder the practical utilization of CDs for water sensing. To tackle such dilemma, a highly water-soluble CDs with distinctive hydrogen-bond-induced emission (HBIE) was rationally designed through introducing sulfone group into the widely employed p-phenylenediamine precursor. The inclusion of sulfone group imparts the CDs with notable water solubility, as well as distinctive ratiometric fluorescent response towards water content, exhibiting high sensitivity and selectivity. Upon exposure to water, the emission color of CDs undergoes a real-time transition from blue to yellow-green, which can be readily discerned by naked eyes. The CDs have been successfully applied in detecting water in commercially available alcohol. This study presents a straightforward yet efficacious approach for rationally design of CDs with unique HBIE characteristics and ratiometric fluorescent response, offering great potential for practical chemosensing applications.

Ketocyanine-Based Fluorescent Probe Revealing the Polarity Heterogeneity of Lipid Droplets and Enabling Accurate Diagnosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has gradually become a pronoun for terrifying death owing to its high mortality rate. With the progression of HCC, lipid droplets (LDs) in HCC cells exhibit specific variations such as increased LDs number and decreased polarity, which can serve as the diagnostic target. However, developing an effective method to achieve HCC diagnosis and reveal LDs polarity heterogeneity is still a crucial challenge. Herein, the first high-performance LDs-targeting probe (1) is reported based on ketocyanine strategy with ultrasensitive polarity-responding ability and near-infrared emission. Probe 1 shows excellent sensitivity to polarity parameter Δf (0.027-0.290) with 808-fold fluorescence enhancement and the emission wavelength red-shifts 91 nm. In HCC cells, probe 1 shows a 2.5- to 5.9-fold fluorescence enhancement compared with normal and other cancer cells which exceeds clinical threshold of 2.0, indicating probe 1 can distinguish HCC cells. The LDs polarity heterogeneity is revealed and it displays a sequence, HCC cells < other cancer cells < normal cells, which may provide useful insight to engineer LDs-targeting probes for HCC cell discrimination. Finally, probe 1 realizes accurate HCC diagnosis on the cellular, organ, and in vivo levels, providing a satisfying tool for clinical HCC diagnosis and surgical navigation.

A Silicon-Rhodamine-Based Heavy-Atom-Free Photosensitizer for Mitochondria-targeted Photodynamic Therapy.

Silicon-xanthene derivatives (SiXs) have gained popularity in the field of bioimaging due to their advantageous far-red to near-infrared (NIR) absorption and emission wavelengths, notable brightness (ε × Φ), inherent mitochondrial targeting properties and high photo-stability, making them an excellent candidate for photodynamic therapy (PDT). Nevertheless, the utilization of SiXs as photosensitizers (PSs) for PDT in cancer treatment remains largely unexplored, primarily due to their limited capacity to generate cytotoxic reactive oxygen species (ROS). However, the potential of SiXs in PDT warrants further investigation. In this study, utilizing the spin-orbit charge transfer-induced intersystem crossing (SOCT-ISC) mechanism, we reported one novel heavy-atom-free, mitochondria-targeted, silicon-rhodamine-based photosensitizer (SiR-PXZ), which demonstrated excellent biocompatibility, minimal dark toxicity, favorable water-solubility and stability, and considerable singlet oxygen quantum yield under 660 nm light irradiation (ΦΔ = 0.16 in air-saturated PBS). Moreover, SiR-PXZ could be rapidly taken up by the mitochondria and efficiently induced apoptosis of cancer cells with an IC50 value of 1.2 µM. The in vivo studies showed that SiR-PXZ exhibited excellent anti-tumor effects, making it potentially valuable for clinical application. This study offers a source of ideas for the construction of SiXs-based photosensitizers for photodynamic cancer treatment in the future.

Light-responsive benzobisthiazole as oxidase mimic for rapid determination of glutathione in food and vegetable.

Accurate determination of glutathione (GSH) in food and vegetable is significant to instruct the appropriate supplementation of GSH in the human body. Light-responsive enzyme mimics have been widely used in detecting GSH due to controllable temporal and spatial accuracy. However, exploring a potential organic mimic enzyme with excellent catalytic efficiency keeps challenging. Herein, a benzobisthiazole organic oxidase mimic was successfully prepared by a simple and low-cost method. Based on its high light-responsive oxidase-like activity, it was used for high reliable colorimetric determination of GSH in food and vegetable for only 1 min with a large linear range of 0.02-30 µM and a low detection limit of 5.3 nM. This study provides a novel strategy to obtain powerful light-responsive oxidase mimics and holds great potential for rapid and accurate detection of GSH in food and vegetables.

Three birds, one stone: Disinfecting and turning waste medical masks into valuable carbon dots for sodium hydrosulfite and Fe3+ detection enabled by a simple hydrothermal treatment.

Disposable medical masks are widely used to prevent respiratory infections due to their ability to block virus particles from entering the human body. The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of medical masks, leading to their widespread use around the world. However, a large number of disposable medical masks have been discarded, some carrying viruses, which have posed a grave threat to the environment and people's health, as well as wasting resources. In this study, a simple hydrothermal method was used for the disinfection of waste medical masks under high-temperature conditions as well as for their transformation into high-value-added carbon dots (CDs, a new type of carbon nanomaterial) with blue-emissive fluorescence, without high energy consumption or environmental pollution. Moreover, the mask-derived CDs (m-CDs) could not only be used as fluorescent probes for sensing sodium hydrosulfite (Na2S2O4), which is widely used in the food and textile industries but is seriously harmful to human health, but also be used for detecting Fe3+ which is harmful to the environment and human health due to its wide use in industries.

Broad-Specificity Screening of Pyrethroids Enabled by the Catalytic Function of Human Serum Albumin on Coumarin Hydrolysis.

Sensing systems based on cholinesterase and carboxylesterase coupled with different transduction technologies have emerged for pesticide screening owing to their simple operation, fast response, and suitability for on-site analysis. However, the broad spectrum and specificity screening of pyrethroids over organophosphates and carbamates remains an unmet challenge for current enzymatic sensors. Human serum albumin (HSA), a multifunctional protein, can promote various chemical transformations and show a high affinity for pyrethroids, which offer a route for specific and broad-spectrum pyrethroid screening. Herein, for the first time, we evaluated the catalytic hydrolysis function of human serum albumin (HSA) on the coumarin lactone bond and revealed that HSA can act as an enzyme to catalyze the hydrolysis of the coumarin lactone bond. Molecular docking and chemical modifications indicate that lysine 199 and tyrosine 411 serve as the catalytic general base and contribute to most of the catalytic activity. Utilizing this enzymatic activity, a broad specific ratiometric fluorescence pyrethroids sensing system was developed. The binding energetics and binding constants of pesticides and HSA show that pyrethroids bind to HSA more easily than organophosphates and carbamates, which is responsible for the specificity of the sensing system. This study provides a general sensor platform and strategy for screening pesticides and reveals the catalytic activity of HSA on the hydrolysis of the coumarin lactone bond, which may open innovative horizons for the chemical sensing and biomedical applications of HSA.

Lysosome Imaging Based on Fluorescent Carbon Dots.

Lysosomes play key roles in different cellular processes such as autophagy, phagocytosis, and apoptosis. Lysosomal dysfunction is related to many diseases. Fluorescence lysosome staining strategy is valuable for the researches on the lysosome involvement in different pathological diagnosis. Here we describe fluorescence lysosome staining methods with carbon dots for the identification of lysosomes in living and fixed cells.

Carbon dots as light-responsive oxidase-like nanozyme for colorimetric detection of total antioxidant capacity in fruits.

Evaluation of total antioxidant capacity (TAC) in fruits is essential for dietary guidance and health monitoring. Here, we have exploited light-response carbon dots (CDs) as oxidase-like nanozyme to determine the TAC of fruits. The CDs possess excellent oxidase-like activity with light stimulation due to the accelerated intramolecular charge transfer caused by abundant electron donating/drawing groups in precursors. The scavenger experiment reveals that the catalytic intermediate could be hydroxyl radical, which can oxidize the colorimetric substrate. With the introduction of antioxidants, the oxidization of colorimetric substrate will be alleviated due to the scavenging of this intermediate by antioxidants. Based on this, we have successfully detected three antioxidants and obtained TAC of fruits with desirable results. This work affords a rapid, cost-effective and convenient analysis tool for TAC, as well as building a strong bridge between CDs and the development of photo-responsive oxidase-like nanozymes.

Natural flavylium-inspired far-red to NIR-II dyes and their applications as fluorescent probes for biomedical sensing.

Fluorescent probes that emit in the far-red (600-700 nm), first near-infrared (NIR-I, 700-900 nm), and second NIR (NIR-II, 900-1700 nm) regions possess unique advantages, including low photodamage and deep penetration into biological samples. Notably, NIR-II optical imaging can achieve tissue penetration as deep as 5-20 mm, which is critical for biomedical sensing and clinical applications. Much research has focused on developing far-red to NIR-II dyes to meet the needs of modern biomedicine. Flavylium compounds are natural colorants found in many flowers and fruits. Flavylium-inspired dyes are ideal platforms for constructing fluorescent probes because of their far-red to NIR emissions, high quantum yields, high molar extinction coefficients, and good water solubilities. The synthetic and structural diversities of flavylium dyes also enable NIR-II probe development, which markedly advance the field of NIR-II in vivo imaging. In the last decade, there have been huge developments in flavylium-inspired dyes and their applications as far-red to NIR fluorescent probes for biomedical applications. In this review, we highlight the optical properties of representative flavylium dyes, design strategies, sensing mechanisms, and applications as fluorescent probes for detecting and visualizing important biomedical species and events. This review will prompt further research not only on flavylium dyes, but also into all far-red to NIR fluorophores and fluorescent probes. Moreover, this interest will hopefully spillover into applications related to complex biological systems and clinical treatments, ranging in focus from the sub-organelle to whole-animal levels.

Visual Monitoring of Nucleic Acid Dynamic Structures during Cellular Ferroptosis Using Rationally Designed Carbon Dots with Robust Anti-Interference Ability to Reactive Oxygen Species.

Ferroptosis triggered by an iron-dependent accumulation of lipid reactive oxygen species (ROS) has drawn widespread attention. Directly visualizing the dynamic structures of nucleic acids during the ferroptosis of cells is of great importance considering their vital roles in numerous biological functions. However, direct imaging remains challenging, largely due to the extremely high concentrations of ROS generated during ferroptosis, which can affect the imaging of nucleic acid targeted fluorescent probes. To overcome this challenge, nucleic acid-responsive carbon dots (CDs) providing favorable optical properties together with high chemical stability were synthesized. Furthermore, the CDs penetrated the cell membrane quickly and accumulated in the nuclei of cells. The robust anti-interference ability to ROS allows the CDs to visualize the dynamic structures of nucleic acids during ferroptosis. Moreover, the CDs were successfully employed in the imaging of nucleic acids during cell division. The nuclei-targeting CDs show great potential as a powerful tool for imaging nuclei in ferroptosis-related biological and clinical research.

High-fidelity carbon dots polarity probes: revealing the heterogeneity of lipids in oncology.

Polarity is an integral microenvironment parameter in biological systems closely associated with a multitude of cellular processes. Abnormal polarity variations accompany the initiation and development of pathophysiological processes. Thus, monitoring the abnormal polarity is of scientific and practical importance. Current state-of-the-art monitoring techniques are primarily based on fluorescence imaging which relies on a single emission intensity and may cause inaccurate detection due to heterogeneous accumulation of the probes. Herein, we report carbon dots (CDs) with ultra-sensitive responses to polarity. The CDs exhibit two linear relationships: one between fluorescence intensity and polarity and the other between polarity and the maximum emission wavelength. The emission spectrum is an intrinsic property of the probes, independent of the excitation intensity or probe concentration. These features enable two-color imaging/quantitation of polarity changes in lipid droplets (LDs) and in the cytoplasm via in situ emission spectroscopy. The probes reveal the polarity heterogeneity in LDs which can be applied to make a distinction between cancer and normal cells, and reveal the polarity homogeneity in cytoplasm.

Mechanisms for carbon dots-based chemosensing, biosensing, and bioimaging: A review.

Due to the favorable biocompatibility, photostability and fluorescence emissions, carbon dots (CDs) are being widely investigated as fluorescent probes. Current CD-based fluorescent probe designs depend largely on conventional fluorescence sensing mechanisms, for e.g. the inner filter effect, photoinduced electron transfer, and Förster resonance energy transfer. Although these mechanisms have been successful, it is still desirable to introduce new sensing mechanisms. In recent years, emerging mechanisms such as aggregation-induced emission, hydrogen-bond induced emission, and intramolecular charge transfer have been developed for CD-based probes. This review summarizes both conventional and emerging mechanisms, and discuss CDs in the context of chemosensing, biosensing, and bioimaging. We provide an outlook for several other mechanisms such as CN isomerization, the short-wavelength inner filter technique, excited-state intramolecular proton transfer, and twisted intramolecular charge transfer, which have been applied to organic fluorescent probes design but not as much in CD-based sensing systems. We envision that this review will provide insights that inspire further development of CD-based fluorescent probes as for biological applications.

Detection, detoxification, and removal of multiply heavy metal ions using a recyclable probe enabled by click and declick chemistry.

The pollution of water with heavy metal ions has generated great concern among both the public and academics due to the high toxicity, persistence, and non-degradability of heavy metals. The detection, detoxification, and removal of heavy metal ions are critical for monitoring water quality and treating polluted water. However, these tasks remain challenging due to lack of effective detection, detoxification, and removal strategies. By combining thiol-triggered click chemistry and heavy metal ion-triggered declick chemistry, a recyclable fluorescent probe for detecting numerous heavy metal ions was successfully developed through simple addition of thiol-containing heavy metal antidote to a carefully selected Michael acceptor-type fluorophore. The probe could be regenerated by adding equal amount of antidote to the detection solution without any purification step recycled up to 10 times. The generated water-soluble heavy metal ion-antidote complexes showed weak toxicity to biological systems, indicating successful detoxification. Finally, a simple, economical, and practical device for detecting, detoxifying, and removing heavy metal ions was fabricated by loading the recyclable fluorescent probe into polymer beads. The percent of detection, and removal are 98.10% and 97.59%, respectively. And detoxification percent is as high as 65.55%. The device is a promising candidate for water quality monitoring and treatment.

Lighting up Individual Organelles With Fluorescent Carbon Dots.

Cell organelles play crucial roles in the normal functioning of an organism, therefore the disruption of their operation is associated with diseases and in some cases death. Thus, the detection and monitoring of the activities within these organelles are of great importance. Several probes based on graphene oxide, small molecules, and other nanomaterials have been developed for targeting specific organelles. Among these materials, organelle-targeted fluorescent probes based on carbon dots have attracted substantial attention in recent years owing to their superior characteristics, which include facile synthesis, good photostability, low cytotoxicity, and high selectivity. The ability of these probes to target specific organelles enables researchers to obtain valuable information for understanding the processes involved in their functions and/or malfunctions and may also aid in effective targeted drug delivery. This review highlights recently reported organelle-specific fluorescent probes based on carbon dots. The precursors of these carbon dots are also discussed because studies have shown that many of the intrinsic properties of these probes originate from the precursor used. An overview of the functions of the discussed organelles, the types of probes used, and their advantages and limitations are also provided. Organelles such as the mitochondria, nucleus, lysosomes, and endoplasmic reticulum have been the central focus of research to date, whereas the Golgi body, centrosome, vesicles, and others have received comparatively little attention. It is therefore the hope of the authors that further studies will be conducted in an effort to design probes with the ability to localize within these less studied organelles so as to fully elucidate the mechanisms underlying their function.

Low Polarity-Triggered Basic Hydrolysis of Coumarin as an AND Logic Gate for Broad-Spectrum Cancer Diagnosis.

The ability to accurately diagnose cancer is the cornerstone of early cancer treatment. The mitochondria in cancer cells maintain a higher pH and lower polarity relative to that in normal cells. A probe that reports signals only when both conditions are met may provide a reliable method for cancer detection with reduced false positives. Here, we construct an AND logic gate fluorescent probe using mitochondrial microenvironments as inputs. Utilizing the hydrolysis of a coumarin scaffold, the probe generates fluorescence signals ("ON") only when high pH (>7.0) and low polarity conditions exist simultaneously. Additionally, the higher mitochondrial membrane potential in cancer cells provides an additional level of selectivity because probe has increased affinity for cancer cell mitochondria. These capabilities endow the probe with a high contrast fluorescence diagnosis ability of cancer at cellular and tissue levels (as high as 51.9 fold), which is far exceeding the clinic threshold of 2.0 fold.

Quantitative Structure-Activity Relationship Enables the Rational Design of Lipid Droplet-Targeting Carbon Dots for Visualizing Bisphenol A-Induced Nonalcoholic Fatty Liver Disease-like Changes.

Lipid droplets (LDs) play indispensable roles in numerous physiological processes; hence, the visualization of the dynamic behavior of LDs in living cells is of great importance in physiological and pathological research. In this article, the quantitative structure-activity relationship (QSAR) theory was employed as an effective design strategy for the development of organelle-targeting carbon dots (CDs). The lipid-water partition coefficient (Log P) of the QSAR was adopted as a key parameter to predict the cellular uptake and subcellular localization of CDs in live cells. By carefully adjusting the molecular structure and lipophilicity of the precursors, p-phenylenediamine-derivatized nucleolus-targeting hydrophilic CDs were converted to lipophilic CDs [4-piperidinoaniline (PA) CDs] with inherent LD-targeting performance. The PA CDs were able to indicate the dynamic behavior of LDs and visualize the changes of bisphenol A-induced nonalcoholic fatty liver disease-like changes in a cellular model. The QSAR strategy of CDs demonstrated here is expected to be increasingly exploited as a powerful design tool for developing various organelle-targeting CDs.

Runx1/miR-26a/Jagged1 signaling axis controls osteoclastogenesis and alleviates orthodontically induced inflammatory root resorption.

BACKGROUND: MicroRNAs (miRNAs) are involved in the regulation of osteoclast biology and several pathogenic progression. This study aimed to identify the role of miR-26a in osteoclastogenesis and orthodontically induced inflammatory root resorption(OIIRR). METHODS: Rat orthodontic tooth movement (OTM) model was established by ligating a closed coil spring between maxillary first molar and incisor, and 50 g orthodontic force was applied to move upper first molar to middle for 7 days. Human periodontal ligament (hPDL) cells were isolated from periodontium of healthy donors, and then subjected to compression force (CF) for 24 h to mimic an in vitro OTM model. The levels of associated factors in vivo and in vitro were measured subsequently. RESULT: The distance of tooth movement was increased and root resorption pits were occurred in rat OTM model. The expression of miR-26a was decreased in vivo and vitro experiments. CF treatment enhanced the secretion of inflammatory factors receptor activator of nuclear factor-kappa B ligand (RANKL) and IL-6, osteoclast marker levels, and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, while miR-26a overexpression reversed these results. Furthermore, miR-26a overexpression inhibited the osteoclastogenesis and rescued the root resorption in OTM rats through inhibition of Jagged1. Additionally, Runx1 could bind to miR-26a promoter and promote its expression, thereby suppressing the osteoclastogenesis. CONCLUSION: We concluded that Runx1/miR-26a/Jagged1 signaling axis restrained osteoclastogenesis and alleviated OIIRR.