Cascade reaction triggered colorimetric array for identification of organophosphorus pesticides congeners.

A modern agriculture uses alternative pest control methods to boost productivity, leading to an accumulation of organophosphorus (OPPs) congeners. This necessitates an intuitive and quick way to identify OPPs congeners. A colorimetric sensor for detecting OPPs congeners using a double-enzyme cascade reaction has been successfully designed and constructed in this study. The OPPs regulate the color changes induced by manganese dioxide nanoflowers (MnO2 NFs) and specific alkaline phosphatases (ALP) during the etching of gold nanopyramids (Au NBPs). The ascorbic acid (AA) produced by ALP hydrolysis inhibits Au NBPs etching by MnO2 NFs oxidized 3, 3', 5, 5'-tetramethylbenzidine (TMB). By inhibiting ALP catalytic activity, OPPs prevent AA formation. In this process, Au NBPs will undergo further etching, resulting in various colors so they can be analyzed semi-quantitatively with the naked eye. It has been found that different types of OPPs inhibit enzymes differently and therefore result in varying degrees of etching of Au NBPs. Principal Component Analysis (PCA) is performed by smart devices that convert R, G, and B signals into digital signals. This colorimetric array tests various foods (tea, apple, and cabbage). Colorimetric visualization sensors combined with data analysis will be used in real-life product development.

Distinguishable Colorimetric Biosensor for Diagnosis of Prostate Cancer Bone Metastases.

Castration-resistant prostate cancer (PCa) causes severe bone metastasis (BM), which significantly increases mortality in men with PCa. Imaging tests and radiometric scanning require long analysis times, expensive equipment, specialized personnel, and a slow turnaround. New visualization technologies are expected to solve the above problems. Nonetheless, existing visualization techniques barely meet the urgency for precise diagnosis because the human eyes cannot recognize and capture even slight variations in visual information. By using dye differentiated superposition enhancement colorimetric biosensors, an effective method to diagnose prostate cancer bone metastases (PCa-BM) with excellent accuracy for naked-eye quantitative detection of alkaline phosphatase (ALP) is developed. The biomarker ALP specific hydrolytic product ascorbic acid can be detected by rhodamine derivatives (Rd) as gold nanobipyramids (Au NBPs) are deposited and grown. Color-recombining enhancement effects between Rd and Au NBPs significantly improved abundance. The 150 U L-1 threshold between normal and abnormal can be identified by color. And with color enhancement effect and double signal response, the ALP index is visually measured to diagnose PCa-BM and provide handy treatment recommendations. Additionally, the proposed colorimetric sensing strategy can be used to diagnose other diseases.

Nanohole-Array Induced Metallic Molybdenum Selenide Nanozyme for Photoenhanced Tumor-Specific Therapy.

Deficient catalytic sensitivity to the tumor microenvironment is a major obstacle to nanozyme-mediated tumor therapy. Electron transfer is the intrinsic essence for a nanozyme-catalyzed redox reaction. Here, we developed a nanohole-array-induced metallic molybdenum selenide (n-MoSe2) that is enriched with Se vacancies and can serve as an electronic transfer station for cycling electrons between H2O2 decomposition and glutathione (GSH) depletion. In a MoSe2 nanohole array, the metallic phase reaches up to 84.5%, which has been experimentally and theoretically demonstrated to exhibit ultrasensitive H2O2 responses and enhanced peroxidase (POD)-like activities for H2O2 thermodynamic heterolysis. More intriguingly, plenty of delocalized electrons appear due to phase- and vacancy-facilitated band structure reconstruction. Combined with the limited characteristic sizes of nanoholes, the surface plasmon resonance effect can be excited, leading to the broad absorption spectrum spanning of n-MoSe2 from the visible to near-infrared region (NIR) for photothermal conversion. Under NIR laser irradiation, metallic MoSe2 is able to induce out-of-balance redox and metabolism homeostasis in the tumor region, thus significantly improving therapeutic effects. This study that takes advantage of phase and defect engineering offers inspiring insights into the development of high-efficiency photothermal nanozymes.

Logic gate-driven dual-index balanced visualization strategy for tumor metastasis diagnosis.

Exfoliated tumor cells are integral to malignant tumors diagnosis. The process of clinical cytology of exfoliation involves several complex steps that require at least two days of preparation. Here, we develop a balanced-etching visual kit based on concentration differences of Glutathione/Glucose (GSH/Glu) to distinguish normal from exfoliated tumor cells rapidly and accurately. The balanced-etching visualization kit can be used to obtain color cards and screen exfoliated tumor cells initially (within 10 min). Furthermore, by utilizing logic gates and machine learning algorithms for RGB extraction of the color card obtained from the kit, accurate screening of exfoliated tumor cells is achieved. Finally, a series of clinical tumor samples, such as urine, pleural fluids, ascites, and gastric fluids, have been validated. With effective experimental methods, accurate disease information, and appropriate therapeutic programs, the novel diagnostic strategy is expected to promote precision medicine.

Dual enzyme induced colorimetric sensor for simultaneous identifying multiple pathogens.

Rapid and accurate identification of foodborne pathogens improves public health. Currently employed methods are time-consuming, sensitive to environmental factors, and complex. This study develops a colorimetric sensor for detecting multiple bacteria with one probe using double-enzyme-induced colorimetry. Based on alkaline phosphatase (ALP) in bacteria decomposes L-ascorbic acid 2-magnesium phosphate salt hydrate into ascorbic acid (AA). Manganese dioxide flowers (MnO2 NFs) can oxidize TMB to etch gold nanorods (Au NRs), which can be inhibited by AA reduction to produce rich colors. Bacteria with varying ALP levels can be identified based on color changes and plasmon resonance wavelength signals produced from Au NRs. Furthermore, the conversion of RGB signals to digital signals and the use of linear discriminant analysis (LDA) allowed 99.57% accuracy in identifying multiple bacteria. It can simultaneously identify five foodborne pathogens across diverse environments (shrimp, meat, milk, etc.). This method may be useful for the rapid and simple identification of foodborne illnesses.

Ratiometric near-infrared upconversion fluorescence sensor for selectively detecting and imaging of Al3.

Near-infrared (NIR) fluorescent probes provide extremely sensitive Al3+ detection for human health purposes. This research develops novel Al3+ response molecules (HCMPA) and NIR upconversion fluorescent nanocarriers (UCNPs), which respond to Al3+ through ratio NIR fluorescence. UCNPs improve photobleaching and visible light lack in specific HCMPA probes. Additionally, UCNPs are capable of ratio response, which will further enhance signal accuracy. The NIR ratiometric fluorescence sensing system has been successfully used to detect Al3+ within the range 0.1-1000 nM with an accuracy limit of 0.06 nM. Alternatively, a NIR ratiometric fluorescence sensing system integrated with a specific molecule can image Al3+ within cells. This study demonstrates that a NIR fluorescent probe is an effective and highly stable method of measuring Al3+ in cells.

Multienzyme-Mimicking Au@Cu2O with Complete Antioxidant Capacity for Reactive Oxygen Species Scavenging.

Most enzyme catalysts are unable to achieve effective oxidation resistance because of the monotonous mimicking function or production of secondary reactive oxygen species (ROS). Herein, the Au@Cu2O heterostructure with multienzyme-like activities is deigned, which has significantly improved antioxidant capacity compared with pure Cu2O for the scavenging of highly cell-damaging secondary ROS, i.e.,·OH. Experiments and theoretical calculations show that the heterostructure exhibits a built-in electric field and lattice mismatch at the metal-semiconductor interface, which facilitate to generate abundant oxygen vacancies, redox couples, and surface electron deficiency. On the one hand, the presence of rich oxygen vacancies and redox couple can enhance the adsorption and activation of oxygen-containing ROS (including O2·- and H2O2). On the other hand, the electron transfer between the electron-deficient Au@Cu2O surface and electron donor would promote peroxide-like activity and avoid producing ·OH. Importantly, endogenous ·OH could be eliminated in both acidic and neutral conditions, which is no longer limited by the volatile physiological environment. Therefore, Au@Cu2O can simulate superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione peroxidase (GPx) to form a complete antioxidant system. The deigned nanoenzyme is explored in the real sample world such as A549 cells and zebrafish. This work provides theoretical and practical strategies for the construction of a complete antioxidant enzyme system.

Ultrasensitive Sandwich-Type SERS-Biosensor-Based Dual Plasmonic Superstructure for Detection of Tacrolimus in Patients.

Tacrolimus (FK506) is widely used in the prevention of organ transplant rejection and the treatment of autoimmune diseases, but it is difficult to detect within the low and narrow concentration range in practical clinical fields. A magnetic plasmonic superstructure-targets-plasmonic superstructure-based sandwich-type SERS biosensor is presented here to ultrasensitively detect FK506 in the blood of organ transplant patients. The spiky Fe3O4@SiO2@Ag flower magnetic superstructure and hollow Ag@Au superstructure enhanced the SERS signals by providing rich sharp tips, cavities, and abundant hot spot gaps. And the magnetic feature makes it easy to concentrate and separate the biological target. Using the designed sandwich-type SERS biosensor, FK506 could be detected within a range of 0.5-20 ng/mL with a detection limit of 0.33 ng/mL. All results indicated that the sandwich-type SERS biosensor has good stability, sensitivity, and anti-interference properties. It is noteworthy that this allowed us to successfully analyze FK506 in the blood of transplant patients, which is in strong agreement with the clinical results. Consequently, the attractive sandwich-type SERS biosensor can be used for the detection of FK506 in real samples, which is promising for clinical diagnosis.

Ratiometrically pH-Insensitive Upconversion Nanoprobe: Toward Simultaneously Quantifying Organellar Calcium and Chloride and Understanding the Interaction of the Two Ions in Lysosome Function.

Calcium and chloride levels are closely related to lysosome dysfunction. However, the simultaneous measurement of calcium (Ca2+) and chloride (Cl-) in acidic subcellular organelles, which is conducive to a deep understanding of lysosome-related biological events, remains a challenge. In this study, we developed a pH-insensitive, ratiometric NIR nanoprobe for the simultaneous detection of Ca2+ and Cl- in acidic lysosomes and determined the roles of the two ions in lysosome function. The upconversion nanoprobe with blue, green, and red emissions was modified with a Ca2+-sensitive dye (Rhod-5N) and Cl--responsive fluorophore (10,10'-bis[3-carboxypropyl]-9,9'-biacridinium dinitrate, BAC). As a result of a dual-luminescence resonance energy transfer between upconversion nanoparticles (UCNPs) and Rhod-5N/BAC, the blue and green upconversion luminescence (UCL) of UCNPs were quenched and the red UCL was used as the reference signal. The ratiometric upconversion nanoprobe possesses a specific ability for the concurrent recognition of Ca2+ and Cl- ions independent of the influence of the environmental pH. To locate the probe in the lysosome, dextran was further modified with upconversion nanoparticles. Then, the nanoprobe with a high spatial resolution was constructed for the simultaneous monitoring of Ca2+ and Cl- in acidic lysosomes. Moreover, it was found that the reduction of lysosomal Cl- affects the release of lysosomal Ca2+, which further blocks the activities of specific lysosomal enzymes. The ratiometric NIR nanoprobe has great potential for decoding and evaluating lysosomal diseases.

Synthesis and Bioapplications of Ag2 S Quantum Dots with Near-Infrared Fluorescence.

Quantum dots (QDs) with near-infrared fluorescence (NIR) are an emerging class of QDs with unique capabilities owing to the deeper tissue penetrability of NIR light compared with visible light. NIR light also effectively overcomes organism autofluorescence, making NIR QDs particularly attractive in biological imaging applications for disease diagnosis. Considering latest developments, Ag2 S QDs are a rising star among NIR QDs due to their excellent NIR fluorescence properties and biocompatibility. This review presents the various methods to synthesize NIR Ag2 S QDs, and systematically discusses their applications in biosensing, bioimaging, and theranostics. Major challenges and future perspectives concerning the synthesis and bioapplications of NIR Ag2 S QDs are discussed.

Ratiometric Upconversion Luminescence Nanoprobe with Near-Infrared Ag2S Nanodots as the Energy Acceptor for Sensing and Imaging of pH in Vivo.

A luminescence resonance energy transfer (LRET) system was successfully developed using near-infrared (NIR) Ag2S nanodots (NDs) as the energy acceptors and upconversion nanoparticles (UCNPs) as the energy donors. The system possessing the properties of NIR excitation (980 nm) and NIR emission (795 nm) was used for the ratiometric detection and bioimaging of pH in tumor cells and zebrafish. Glutathione and mercaptopropionic acid (MPA) co-modified Ag2S NDs (GM-Ag2S NDs) were prepared by ligand exchange with an excellent pH-responsive property over a pH range of 4.0 to 9.0. The NIR GM-Ag2S NDs were covalently grafted with silica coated UCNPs, and an efficient LRET platform was developed via modulation of the thickness of the silica coating. Due to the LRET process between UCNPs and GM-Ag2S NDs, a ratiometric luminescence nanoprobe with the properties of NIR excitation-NIR emission was constructed for pH biosensing and bioimaging. On the basis of high contrast bioimaging, the nanoplatform can distinguish between tumor and normal tissue in the zebrafish model.

A ratiometric fluorescent assay for the detection and bioimaging of alkaline phosphatase based on near infrared Ag2S quantum dots and calcein.

Herein, a ratiometric fluorescent method was developed for alkaline phosphatase (ALP) detection based on near-infrared (NIR) Ag2S quantum dots (QDs) and calcein through the competitive approach. The system based on Ag2S QDs and calcein shows green (maximum emission at 512 nm from calcein) and near infrared (NIR) fluorescence (maximum 798 nm from Ag2S QDs) under the same excitation wavelength (468 nm). In the presence of Ce3+, the fluorescence intensity of calcein is decreased due to static quenching, while the fluorescence intensity of Ag2S QDs is enhanced through aggregation induced emission (AIE). The p-nitrophenyl phosphate is hydrolyzed by ALP, and the yield phosphate ions bind with Ce3+ with higher affinity than these of Ag2S QDs and calcein. Therefore, the green fluorescence from calcein is recovered while NIR fluorescence from Ag2S QDs is decreased. On the basis of these findings, a ratiometric fluorescence assay was developed for the measurement of ALP activity. The ratio of fluorescence intensity at 512 and 798 nm (F512/F798) was well associated with the ALP concentration ranging from 2 to 100 mU/mL with the detection limit of 1.28 mU/mL. The method was successfully applied for detecting ALP in human serum with an acceptable recovery and bioimaging intracellular ALP with good performance. In addition, the approach was also employed for the screening ALP inhibitor.

Label-free fluorometric assay for cytochrome c in apoptotic cells based on near infrared Ag2S quantum dots.

As an important biomarker, cytochrome c (Cyt c) plays a crucial role in mitochondrial electron transport chain and cell apoptosis. Herein, a label-free near-infrared (NIR) Ag2S quantum dots (QDs)-based fluorescent strategy was constructed for the sensitive and selective detection of Cyt c. In this system, Cyt c was hydrolyzed by trypsin, and the resulting heme-peptide fragment exhibited peroxidase-like activity for catalytic decomposition of H2O2 into hydroxyl radical (·OH). The presence of caffeic acid in this system resulted into the formation of caffeic acid-quinone due to the strong oxidizing ability of ·OH. The production of caffeic acid-quinone led to the fluorescence quenching of Ag2S QDs through electron transfer mechanism. Based on the cascade reaction, we successfully developed a label-free approach to detect Cyt c using Ag2S QDs as nanoprobes. Under the optimized conditions, the fluorescence intensity of Ag2S QDs was linearly relative to the concentration of Cyt c over the range from 2.0 to 150 nM with a detection limit of 1.7 nM. In addition, this strategy was successfully applied for quantitative detection of Cyt c in cell lysates of H2O2 or etoposide (anticancer drug)-induced apoptotic cells, providing great potential application for cell-based oxidation pressure determination and screening of anticancer drugs.

Near-Infrared Fluorescent Ag2S Nanodot-Based Signal Amplification for Efficient Detection of Circulating Tumor Cells.

The level of circulating tumor cells (CTCs) plays a critical role in tumor metastasis and personalized therapy, but it is challenging for highly efficient capture and detection of CTCs because of the extremely low concentration in peripheral blood. Herein, we report near-infrared fluorescent Ag2S nanodot-based signal amplification combing with immune-magnetic spheres (IMNs) for highly efficient magnetic capture and ultrasensitive fluorescence labeling of CTCs. The near-infrared fluorescent Ag2S nanoprobe has been successfully constructed through hybridization chain reactions using aptamer-modified Ag2S nanodots, which can extremely improve the imaging sensitivity and reduce background signal of blood samples. Moreover, the antiepithelial-cell-adhesion-molecule (EpCAM) antibody-labeled magnetic nanospheres have been used for highly capture rare tumor cells in whole blood. The near-infrared nanoprobe with signal amplification and IMNs platform exhibits excellent performance in efficient capture and detection of CTCs, which shows great potential in cancer diagnostics and therapeutics.

Transition metal dichalcogenide quantum dots: synthesis, photoluminescence and biological applications.

The unique electronic, physical and chemical properties of nanostructured transition metal dichalcogenide (TMD) materials have received great attention, specifically, with the decrease of size to several nanometers, particles named TMD quantum dots (QDs). The inherent properties of TMD QDs make them promising for a variety of applications, including catalytic, luminescence and biomedical. In this review, we first briefly introduce the controlled synthesis of TMD QDs using mechanical exfoliation, ion intercalation-assisted liquid exfoliation, free radical and electrochemical shear and hydrothermal/solvothermal reaction. We then summarize recent progress on chemical and biological applications of TMD QDs in detail.

Rare earth ions enhanced near infrared fluorescence of Ag2S quantum dots for the detection of fluoride ions in living cells.

In this work, a novel phenomenon was discovered that the fluorescence intensity of silver sulfide quantum dots (Ag2S QDs) could be enhanced in the presence of rare earth ions through aggregation-induced emission (AIE). Based on the strong coordination between rare earth ions and F-, a facile and label-free strategy was developed for the detection of F- in living cells. Ag2S QDs were synthesized using 3-mercaptopropionic acid as sulfur source and stabilizer in aqueous solution. The near infrared (NIR) emitting QDs exhibited excellent photostalilty, high quantum yield and low toxic. Interestingly, the fluorescence intensity of QDs was obviously enhanced upon the addition of various rare earth ions, especially in the presence of Gd3+. The AIE mechanism was proved via the TEM, zeta potential and dynamic light scattering analysis. Moreover, the coordination between rare earth ions and F- could lead to the quenching of fluorescence QDs due to the weakening the AIE. Based on these findings, we developed a highly sensitive and selective method for detection of F-. The label-free NIR fluorescence probe was successfully used for F- bioimaging in live cells.

Black Phosphorus Quantum Dots as the Ratiometric Fluorescence Probe for Trace Mercury Ion Detection Based on Inner Filter Effect.

In this work, a novel ratiometric fluorescence sensor has been constructed for the selective and sensitive detection of Hg2+, which is based on the inner filter effect (IFE) of tetraphenylporphyrin tetrasulfonic acid (TPPS) toward black phosphorus quantum dots (BP QDs). Highly fluorescent BP QDs were successfully synthesized from bulk BP by sonication-assisted solvothermal method via a top-down route. In the presence of Hg2+, the IFE originating from spectral overlap between the excitation of BP QDs and the absorption of TPPS is inhibited and the fluorescence of BP QDs is restored. At the same time, the red fluorescence of TPPS is quenched due to its coordination with Mn2+. These phenomena result from the rapid coordination between Mn2+ and TPPS in the presence of Hg2+, which leads to the dramatic decrease of the absorption of TPPS. On the basis of these findings, we design a ratiometric fluorescence sensor for the detection of Hg2+. The as-constructed sensor reveals a good linear response to Hg2+ ranging from 1 to 60 nM with a detection limit of 0.39 nM. Furthermore, the sensing assay is applicable to detecting Hg2+ in real samples.

One-step synthesis of DNA functionalized cadmium-free quantum dots and its application in FRET-based protein sensing.

DNA functionalized quantum dots (QDs) are promising nanoprobes for the fluorescence resonance energy transfer (FRET)-based biosensing. Herein, cadmium-free DNA functionalized Mn-doped ZnS (DNA-ZnS:Mn2+) QDs were successfully synthesized by one-step route. As-synthesized QDs show excellent photo-stability with the help of PAA and DNA. Then, we constructed a novel FRET model based on the QDs and WS2 nanosheets as the energy donor-acceptor pairs, which was successfully applied for the protein detection through the terminal protection of small molecule-linked DNA assay. This work not only explores the potential bioapplication of the DNA-ZnS:Mn2+ QDs, but also provides a platform for the investigation of small molecule-protein interaction.

One-Step Synthesis of Water-Soluble MoS2 Quantum Dots via a Hydrothermal Method as a Fluorescent Probe for Hyaluronidase Detection.

In this work, a bottom-up strategy is developed to synthesize water-soluble molybdenum disulfide quantum dots (MoS2 QDs) through a simple, one-step hydrothermal method using ammonium tetrathiomolybdate [(NH4)2MoS4] as the precursor and hydrazine hydrate as the reducing agent. The as-synthesized MoS2 QDs are few-layered with a narrow size distribution, and the average diameter is about 2.8 nm. The resultant QDs show excitation-dependent blue fluorescence due to the polydispersity of the QDs. Moreover, the fluorescence can be quenched by hyaluronic acid (HA)-functionalized gold nanoparticles through a photoinduced electron-transfer mechanism. Hyaluronidase (HAase), an endoglucosidase, can cleave HA into proangiogenic fragments and lead to the aggregation of gold nanoparticles. As a result, the electron transfer is blocked and fluorescence is recovered. On the basis of this principle, a novel fluorescence sensor for HAase is developed with a linear range from 1 to 50 U/mL and a detection limit of 0.7 U/mL.

A facile and one-step ethanol-thermal synthesis of MoS2 quantum dots for two-photon fluorescence imaging.

Two-photon fluorescent (TPF) molybdenum disulfide quantum dots (MoS2 QDs) were synthesized through a facile and one-step solvothermal approach. The MoS2 QDs exhibit small size and high stability. Because of their low toxicity and TPF ability, the MoS2 QDs are successfully applied in two-photon fluorescence bio-imaging.