A novel fluorescent probe with aggregation induced emission (AIE) effect based on 1,4-dihydropyridine and its applications.

A fluorescent hydrazine hydrate probe (DMA) based on 1,4-dihydropyridine derivatives was designed and synthesized. The fluorescence emission peak of this probe is in the near-infrared region (667 nm), which has good selectivity to hydrazine hydrate and low detection limit (11 nM). Importantly, the probe exhibits aggregation-induced emission (AIE) characteristics. In addition, the probe is prepared with a portable test paper to realize the identification of hydrazine hydrate in the solution and the quantitative detection of hydrazine hydrate gas.

A novel ratiometric fluorescent probe for differential detection of HSO3- and ClO- and application in cell imaging and tumor recognition.

By connecting 1,8-naphthalimide and indole sulfonate, a ratio fluorescent probe capable of differential detection of hydrogen sulfite and hypochlorite was synthesized for the first time. It was able to achieve the qualitative detection of HSO3- and ClO- with high sensitivity and selectivity, respectively. It provides a multi-purpose probe and is based on different emission channels without mutual interference. The probe has the advantages of larger Stokes shift (ClO-: 115 nm, HSO3-: 88 nm), longer λem (ClO-: 515 nm, HSO3-: 548 nm) and better water solubility (DMF/PBS = 1:99, v/v). In addition, the probe is a ratio fluorescence probe, which can detect fluorescence intensity with two different emission waves. It provides internal self-calibration, reduces interference from the background and increases detection accuracy. In vitro cytotoxicity and imaging experiments show that the probe can effectively perform the detection of exogenous HSO3- and ClO- in cells. It can also achieve the detection of HSO3- and ClO- in the plasma environment. Because the probe can detect endogenous ClO-, it also has a good prospect for biological application in identifying tumor cells. Graphical abstract.

An innovative fluorescent probe based on dicyanoisoflurone derivatives for differential detection of Hg2+ and Cu2+ and its applications in bacteria, cell imaging and food analysis.

BACKGROUND: Heavy metal pollution has become one of the world's most important environmental pollution, especially Hg2+ is enriched, it is easy to enter the human body through the food chain, bind to the sulfhydryl group in the protein, cause mercury poisoning. Traditional methods for detecting Hg2+ have obvious drawbacks, such as poor selectivity and long detection time. Fluorescence detection has attracted attention because of its good sensitivity and specificity detection ability. In previously reported probes for detecting Hg2+, Cu2+ often interferes. Therefore, it is of great practical significance to synthesize a fluorescent probe that can distinguish between Hg2+ and Cu2+. RESULTS: We have successfully synthesized the probe DFS, a fluorescent probe that can differentially detect Hg2+ and Cu2+, and the probe DFS has good selectivity and anti-interference ability for Hg2+ and Cu2+. The fluorescence intensity at 530 nm increased rapidly when Hg2+ was detected; during the Cu2+ detection, the fluorescence intensity at 636 nm gradually decreased, fluorescence quenching occurred, and the detection limits of Hg2+ and Cu2+ were 7.29 × 10-9 M and 2.13 × 10-9 M, respectively. Through biological experiments, it was found that probe DFS can complete the fluorescence imaging of Hg2+ and Cu2+ in Staphylococcus aureus and HUVEC cells, which has certain research value in the field of environmental monitoring and microbiology, and the probe DFS has low cytotoxicity, so it also has broad application prospects in the field of biological imaging. In addition, the probe DFS also has good applicability for Hg2+ and Cu2+ detection in actual samples. SIGNIFICANCE AND NOVELTY: This is a fluorescent probe that can distinguish between Hg2+ and Cu2+, the fluorescence emission peak appears at 530 nm when Hg2+ is detected; when detecting Cu2+, fluorescence quenching occurs at 636 nm, the fluorescence emission peak distance between Hg2+ and Cu2+ differs by 106 nm. This reduces mutual interference between Hg2+ and Cu2+ during detection, it provides a new idea for the detection of Hg2+ and Cu2+.

An innovative near-infrared fluorescent probe with FRET effect for the continuous detection of Zn2+ and PPi with high sensitivity and selectivity, and its application in bioimaging.

As the second most abundant transition metal element in the human body, zinc ions play an important role in the normal growth and development of the human body. We have successfully synthesized a near-infrared fluorescent probe with FRET effect for the detection of Zn2+. Probe DR6G has good selectivity and anti-interference ability for Zn2+. When Zn2+ is added to the probe DR6G solution, it responds completely within seconds, releasing red fluorescence with a detection limit of 2.02 × 10-8 M. As the main product of ATP hydrolysis, PPi is indispensable in various metabolic activities in cells and the human body. Due to the strong binding ability of Zn2+ and PPi, it is easy to form ZnPPi precipitation, so we added PPi to the solution to complete the Zn2+ detection, and realized the continuous detection of PPi, and the detection limit was 2.06 × 10-8 M. Since Zn2+ and PPi play an important role in vivo, it is of great practical significance to design and synthesize a fluorescent probe that can continuously detect Zn2+ and PPi. Biological experiments have shown that the probe DR6G has low cytotoxicity and can complete the detection of exogenous Zn2+ and PPi in cells and living mice in vitro. Bacterial experiments have shown that the DR6G probe also has certain research value in the field of environmental monitoring and microbiology. Due to the constant variation of the fluorescence signals of Zn2+ and PPi during detection, we designed the logic gate program. In practical applications, the probe DR6G can quantitatively detect Zn2+ in zinc-containing oral liquids and qualitatively detect PPi in toothpaste.

A novel "on-off-on" near-infrared fluorescent probe for Cu2+ and S2- continuous detection based on dicyanoisoflurone derivatives, and its application in bacterial imaging.

We have successfully synthesized a near-infrared fluorescent probe for the continuous detection of copper and sulfur ions. The probe has good selectivity and anti-interference ability against Cu2+ and S2-. The results show that after adding Cu2+ to the DL solution of the near-infrared fluorescent probe, Cu2+ forms a [DL + Cu2+] complex with the probe, which leads to fluorescence quenching due to the paramagnetism of Cu2+. The probe can be used for the quantitative detection of Cu2+ with a detection limit of 1.26 × 10-9 M. According to the Job's plot curve the binding stoichiometry between DL and Cu2+ is 1 : 1. Subsequently, S2- was added to the [DL + Cu2+] solution, because the precipitation dissolution equilibrium constant of CuS was Ksp = 1.27 × 10-36, so the binding capacity between Cu2+ and S2- was stronger, CuS precipitation was formed, and red fluorescence was re-released, and the quantitative detection of S2- was realized, and the detection limit was 3.50 × 10-8 M. Through bacterial imaging experiments, we found that the probe can accomplish the fluorescence imaging experiments of Staphylococcus aureus, indicating that the probe has good biopenetration and biocompatibility, and has application prospects in bioimaging and environmental monitoring. In addition, the probe DL has good suitability for Cu2+ and S2- detection in real samples.

Stromal cells in the tumor microenvironment: accomplices of tumor progression?

The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), and cellular components include cancer cells and non-malignant cells such as immune cells and stromal cells. These three types of cells establish complex signals in the body and further influence tumor genesis, development, metastasis and participate in resistance to anti-tumor therapy. It has attracted scholars to study immune cells in TME due to the significant efficacy of immune checkpoint inhibitors (ICI) and chimeric antigen receptor T (CAR-T) in solid tumors and hematologic tumors. After more than 10 years of efforts, the role of immune cells in TME and the strategy of treating tumors based on immune cells have developed rapidly. Moreover, ICI have been recommended by guidelines as first- or second-line treatment strategies in a variety of tumors. At the same time, stromal cells is another major class of cellular components in TME, which also play a very important role in tumor metabolism, growth, metastasis, immune evasion and treatment resistance. Stromal cells can be recruited from neighboring non-cancerous host stromal cells and can also be formed by transdifferentiation from stromal cells to stromal cells or from tumor cells to stromal cells. Moreover, they participate in tumor genesis, development and drug resistance by secreting various factors and exosomes, participating in tumor angiogenesis and tumor metabolism, regulating the immune response in TME and extracellular matrix. However, with the deepening understanding of stromal cells, people found that stromal cells not only have the effect of promoting tumor but also can inhibit tumor in some cases. In this review, we will introduce the origin of stromal cells in TME as well as the role and specific mechanism of stromal cells in tumorigenesis and tumor development and strategies for treatment of tumors based on stromal cells. We will focus on tumor-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), tumor-associated adipocytes (CAAs), tumor endothelial cells (TECs) and pericytes (PCs) in stromal cells.

Shear Stress and ROS Dual-Responsive RBC-Hitchhiking Nanoparticles for Atherosclerosis Therapy.

Atherosclerosis (AS), a leading cause of death worldwide, is a chronic inflammatory disease rich in lipids and reactive oxygen species (ROS) within plaques. Therefore, lowering lipid and ROS levels is effective in treating AS and reducing AS-induced mortality. In this study, an intelligent biomimetic drug delivery system that specifically responded to both shear stress and ROS microenvironment was developed, consisting of red blood cells (RBCs) and cross-linked polyethyleneimine nanoparticles (SA PEI) loaded with a lipid-lowering drug simvastatin acid (SA), and RBCs were self-assembled with SA PEI to obtain biresponsive SA PEI@RBCs for the treatment of AS. SA PEI could achieve sustained release of SA in response to ROS and reduce ROS and lipid levels to achieve the purpose of treating AS. Shear stress model experiments showed that SA PEI@RBCs could respond to the high shear stress level (100 dynes/cm2) at plaques, realizing the desorption and enrichment of SA PEI and improving the therapeutic efficiency of SA PEI@RBCs. In vitro and in vivo experiments have confirmed that SA PEI@RBCs exhibits better in vivo safety and therapeutic efficacy than SA PEI and free SA. Therefore, shaping SA PEI@RBCs into a biomimetic drug delivery system with dual sensitivity to ROS and shear stress is an effective strategy and treatment to facilitate their delivery into plaques.

Advances in electrospun nanofibrous membrane sensors for ion detection.

Harmful metal ions and toxic anions produced in industrial processes cause serious damage to the environment and human health. Chemical sensors are used as an efficient and convenient detection method for harmful ions. Electrospun fiber membranes are widely used in the field of solid-state chemical sensors due to high specific surface area, high porosity, and strong adsorption. This paper reviews the solid-state chemical sensors based on electrospinning technology for the detection of harmful heavy metal ions and toxic anions in water over the past decade. These electrospun fiber sensors have different preparation methods, sensing mechanisms, and sensing properties. The preparation method can be completed by physical doping, chemical modification, copolymerization, surface adsorption and self-assembly combined with electrospinning, and the material can also be combined with organic fluorescent molecules, biological matrix materials and precious metal materials. Sensing performance aspects can also be manifested as changes in color and fluorescence. By comparing the literature, we summarize the advantages and disadvantages of electrospinning technology in the field of ion sensing, and discuss the opportunities and challenges of electrospun fiber sensor research. We hope that this review can provide inspiration for the development of electrospun fiber sensors.

A novel Near-Infrared fluorescent probe for Zn2+ and CN- double detection based on dicyanoisfluorone derivatives with highly sensitive and selective, and its application in Bioimaging.

We have successfully synthesized NIRF as a near-infrared fluorescence probe for relay recognition of zinc and cyanide ions. The probe possesses well selectivity and anti-interference ability over common ions towards Zn2+ and CN-. The results showed that Zn2+ and the probe formed [NIRF-Zn2+] complex after added Zn2+ into the probe NIRF solution, which emited red fluorescence. The probe can be used for quantitative detection of Zn2+ with a detection limit of 4.61 × 10-8 M. It was determined that the binding stoichiometry between the NIRF and Zn2+ was 1:1 according to the job,s curve. Subsequently, CN- was added to the NIRF-Zn2+ solution, CN- combined with Zn2+ to generate [Zn(CN-)x]1-x due to the stronger binding ability between zinc ion and cyanogen, which lead to the red fluorescence disappeared. The quantitative detection of CN- was realized with a detection limit of 7.9 × 10*7 M. In addition, the probe has excellent specificity and selectivity for Zn2+ and CN-. And the probe can be stable in a wide range of pH. Through biological experiments, we found that it can complete cell imaging in macrophages and imaging of living mice, which has application prospects in Bioimaging. In addition, the probe NIRF has good applicability for Zn2+ and CN- detection in actual samples.

A novel fluorescent probe based on a triphenylamine derivative for the detection of HSO3- with high sensitivity and selectivity.

A novel highly active fluorescence chemical sensor (TBQN) for HSO3- was synthesized by the Knoevenagel reaction based on triphenylamine-benzothiazole as a new fluorophore. The probe possessed good selectivity toward HSO3- and anti-interference ability with common ions. The fluorescence and UV-vis spectra of the TBQN probe were significantly changed after the addition of HSO3-. At the same time, the probe solution released obvious green fluorescence. Moreover, the limit of detection for HSO3- was calculated to be 3.19 × 10-8 M. The TBQN probe displayed a rapid response to HSO3- and it took about 3 min to complete the recognition. The detection mechanism is the nucleophilic addition reaction between HSO3- and -C[double bond, length as m-dash]C- in the probe molecule. The π-conjugation and ICT (intramolecular charge transfer) transition in the TBQN molecule were destroyed by this addition, which resulted in the change of the fluorescence before and after the addition of HSO3-. Then, the mechanism was verified by theoretical calculations, 1H NMR measurements and mass spectroscopy. In addition, the probe showed low cytotoxicity and could be used for biological imaging in RAW264.7 cells.

A novel hydrophilic fluorescent probe for Cu2+ detection and imaging in HeLa cells.

Copper is an essential element in living systems and plays an important role in human physiology; therefore, methods to detect the concentration of copper ions in living organisms are important. Herein, we report a highly water-soluble naphthalimide-based fluorescent probe that can be used for the detection of Cu2+. The probe, BNQ, has high selectivity and sensitivity. The fluorescence intensity of the probe at 520 nm was visible to the naked eye under a UV lamp; upon the gradual addition of Cu2+, there was a colour change from green to nearly colourless. Furthermore, the detection limit of BNQ for Cu2+ was 45.5 nM. The detection mechanism was investigated using a Job's plot and density functional theory (DFT) calculations. In addition, owing to great biocompatibility, we were able to successfully use BNQ to detect Cu2+ in living HeLa cells with low toxicity.

A novel 100% aqueous solution near-infrared ratiometric fluorescent CN- probe based on 1,4-dihydropyridines, with a large fluorescent emission peak shift.

1,4-Dihydropyridines are a class of drugs with a wide range of biological activities and pharmacological effects. However, there are few reports on its optical activity, especially its application on fluorescent CN- probe. In this experiment, we designed and synthesized a fluorescent probe based on 1,4-dihydropyridines to detect CN-. Interestingly, the probe exhibited outstanding properties such as 100% water soluble, near infrared, ratiometric, fast response, high selectivity and anti-interference ability for other ions. The color change indicated that the probe can be used for naked eye identification. In particular, the probe showed a super large fluorescent emission peak shift (260 nm). In addition, the reaction mechanism of the probe has been studied by 1H NMR titration, high resolution mass spectrometry and theoretical calculations.