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.

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.

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.

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.

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.

[Clinical significance of protein Z detection in patients with malignant tumors].

BACKGROUND & OBJECTIVE: The blood of the patients with malignant tumors is in hypercoagulable state; its correlation to tumor migration evokes more and more attentions. Protein Z (PZ), a newly found anti-coagulation factor, is a vitamin K-dependent plasma protein which is synthesized by the liver. Its structure is very similar to the vitamin K-dependent coagulation factors, such as FXII, FIX, FX, and protein C, but its physiologic function and clinical significance are unclear. The alteration of PZ level correlates with the increased risk of coagulating abnormality-caused diseases, but its alteration in solid tumors is seldom reported. This study was to explore clinical significance of PZ and the correlation of PZ level to FXII:C; FIX:C and FX:C levels in malignant tumors. METHODS: Plasma levels of PZ, FXII:C, FIX:C, FX:C, and FX:Ag of 80 patients with malignant tumors (MT group) and 80 healthy donors (control group) were detected; their correlations were analyzed. RESULTS: The level of PZ was significantly lower in MT group than in control group [(1 210.89+/-251.13) ng/ml vs. (2,378.83+/-429.51) ng/ml, P<0.01], but the levels of FXII:C, FX:C, and FX:Ag were significantly higher in MT group than in control group [(162.42+/-36.57)% vs. (114.78+/-28.96)%, (120.27+/-33.96)% vs. (79.23+/-19.46)%, and (133.66+/-35.51)% vs. (93.0+/-17.73)%, P<0.01]. The levels of FIX:C were (119.86+/-56.38)% in MT group, and (109.21+/-36.46)% in control group (P>0.05). The level of PZ was negatively correlated with the levels of FXII:C; FX:C, and FX:Ag (P<0.01), but had no correlation with the level of FIX:C (P>0.05). The level of PZ was significantly lower in stage III-IV (locally advanced stage-advanced stage) patients than in stage II patients [(998.32+/-117.72) ng/ml vs. (1,326.69+/-245.70) ng/ml, P<0.01], but the levels of FXII:C, FX:C, and FX:Ag were significantly higher in stage III-IV patients than in stage II patients [(206.76+/-28.63)% vs. (136.09+/-26.80)%, (162.53+/-32.92)% vs. (101.89+/-23.44)%, (168.03+/-25.97)% vs. (105.41%+/-13.86)%, P<0.01]. CONCLUSIONS: PZ level is obviously decreased in the patients with malignant tumors, and negatively correlated with FXII:C, FX:C, and FX:Ag. PZ level descends along with the progression of malignant tumors, and maybe a poor prognostic factor of malignant tumors.