A Pretreatment‐Free,Polymer‐Based Platform Prepared by Molecular Imprinting and Post‐Imprinting Modifications for Sensing Intact Exosomes

Exosomes are small (30–100 nm) membrane vesicles that serve as regulatory agents for intercellular communication in cancers. Currently, exosomes are detected by immuno‐based assays with appropriate pretreatments like ultracentrifugation and are time consuming (>12 h). We present a novel pretreatment‐free fluorescence‐based sensing platform for intact exosomes, wherein exchangeable antibodies and fluorescent reporter molecules were aligned inside exosome‐binding cavities. Such antibody‐containing fluorescent reporter‐grafted nanocavities were prepared on a substrate by well‐designed molecular imprinting and post‐imprinting modifications to introduce antibodies and fluorescent reporter molecules only inside the binding nanocavities, enabling sufficiently high sensitivity to detect intact exosomes without pretreatment. The effectiveness of the system was demonstrated by using it to discriminate between normal exosomes and those originating from prostate cancer and analyze exosomes in tear drops.     

A Programmable Signaling Molecular Recognition Nanocavity Prepared by Molecular Imprinting and Post‐Imprinting Modifications

Inspired by biosystems, a process is proposed for preparing next‐generation artificial polymer receptors with molecular recognition abilities capable of programmable site‐directed modification following construction of nanocavities to provide multi‐functionality. The proposed strategy involves strictly regulated multi‐step chemical modifications: 1) fabrication of scaffolds by molecular imprinting for use as molecular recognition fields possessing reactive sites for further modifications at pre‐determined positions, and 2) conjugation of appropriate functional groups with the reactive sites by post‐imprinting modifications to develop programmed functionalizations designed prior to polymerization, allowing independent introduction of multiple functional groups. The proposed strategy holds promise as a reliable, affordable, and versatile approach, facilitating the emergence of polymer‐based artificial antibodies bearing desirable functions that are beyond those of natural antibodies.     

Molecularly Engineered Macrophage‐Derived Exosomes with Inflammation Tropism and Intrinsic Heme Biosynthesis for Atherosclerosis Treatment

Atherosclerosis (AS) is a major contributor to cardiovascular diseases worldwide, and alleviating inflammation is a promising strategy for AS treatment. Here, we report molecularly engineered M2 macrophage‐derived exosomes (M2 Exo) with inflammation‐tropism and anti‐inflammatory capabilities for AS imaging and therapy. M2 Exo are derived from M2 macrophages and further electroporated with FDA‐approved hexyl 5‐aminolevulinate hydrochloride (HAL). After systematic administration, the engineered M2 Exo exhibit excellent inflammation‐tropism and anti‐inflammation effects via the surface‐bonded chemokine receptors and the anti‐inflammatory cytokines released from the anti‐inflammatory M2 macrophages. Moreover, the encapsulated HAL can undergo intrinsic biosynthesis and metabolism of heme to generate anti‐inflammatory carbon monoxide and bilirubin, which further enhance the anti‐inflammation effects and finally alleviate AS. Meanwhile, the intermediate protoporphyrin IX (PpIX) of the heme biosynthesis pathway permits the fluorescence imaging and tracking of AS.     

基于分子印迹技术的吸附材料制备与应用进展

在简要介绍超分子理论的基础上,综述了分子印迹微球和分子印迹膜的制备方法,介绍了其在吸附金属、吸附脱硫、吸附有机小分子以及吸附蛋白质等方面的应用进展。     

Boronate‐Affinity Glycan‐Oriented Surface Imprinting: A New Strategy to Mimic Lectins for the Recognition of an Intact Glycoprotein and Its Characteristic Fragments

Lectins possess unique binding properties and are of particular value in molecular recognition. However, lectins suffer from several disadvantages, such as being hard to prepare and showing poor storage stability. Boronate‐affinity glycan‐oriented surface imprinting was developed as a new strategy for the preparation of lectin‐like molecularly imprinted polymers (MIPs). The prepared MIPs could specifically recognize an intact glycoprotein and its characteristic fragments, even within a complex sample matrix. Glycan‐imprinted MIPs could thus prove to be powerful tools for important applications such as proteomics, glycomics, and diagnostics.     

基于分子印迹电聚合膜的双酚A电化学传感器

以双酚A为模板分子,邻氨基苯硫酚为单体,采用自组装和电聚合方法,在电极表面制备了对双酚A有选择性的分子印迹聚合物膜.通过循环伏安法研究传感器对双酚A的响应特性.结果表明: 在6.0×10-7～5.5×10-5 mol/L浓度范围内峰电流值与浓度呈良好线性关系(r=0.991);检出限2.0×10-7 mol/L; 相对标准偏差<5%(n=9),达到稳定电流所用时间约2 min.此传感器具有良好的选择性、重现性及稳定性.通过交流阻抗技术和计时电流法表征了电极表面膜的电化学性质.将传感器初步用于实际样品的分析,获得了较满意的结果.     

Catalytic Activity of Copper(II) Enzyme-like Catalysts,Prepared by Molecular Imprinting Technique in Oxidation of Phenols

Summary: Molecularly imprinted polymer copper(II) catalysts were prepared by suspension polymerization of 4-vinylpyridine, trimethylolpropane trimethacrylate (series A) and additional monomer – acrylonitrile (series B) in the presence of Cu(II) ions and template: 4-metoxybenzyl alcohol; two samples were also prepared by surface molecular imprinting technique utilizing W/O emulsion. The catalytic activity was tested in model oxidation reactions of hydroquinone and 2,5-di-tert-butylhydroquinone using hydrogen peroxide. The imprinted catalysts were more effective in both reactions than non-imprinted but their activity strongly depended on Cu(II) loading. Surface imprinted samples showed the highest activity (L_H up to 100%).     

Semi‐Covalent Surface Molecular Imprinting of Polymers by One‐Stage Mini‐emulsion Polymerization: Glucopyranoside as a Model Analyte

This paper describes a new type of surface imprinting technique that combines the advantages of both the semi‐covalent approach and one‐stage miniemulsion polymerization. This process has been successfully applied for the preparation of glucose surface‐imprinted nanoparticles. The selective artificial receptors for glucopyranoside were fully characterized by IR, TEM and BET analyses, and their molecular recognition abilities by binding experiments carried out in batch processes. The molecular affinity and selectivity of the glucose molecularly imprinted polymers were accurately quantified. These characteristics are essential for verification of the efficiency of the developed surface imprinting process. The imprinting effect was clearly demonstrated using the batch rebinding method. We have found that the glucose imprinted polymers produced using the optimized one‐stage mini‐emulsion exhibited quite fast kinetics of binding and equilibration with glucopyranoside templates, compared to polymers prepared by bulk polymerization technique, as well as extremely low levels of unspecific bindings. We also demonstrated that glucose molecular imprinted polymer (MIP) exhibited very good selectivity for its original template compared to other glycopyranoside derivatives, such as galactose. Finally, the extraction of the binding properties from isotherms of binding by fitting to the bi‐Langmuir and Freundlich models allowed the determination of the affinity constant distribution of the binding sites. This imprinting protocol allowed the determination of an affinity constant (K_D), involving exclusively H‐bonding interactions, for the glucose MIP ( P2C ) with the best template 1 , in CH₃CN as the solvent system.

     

Outer‐Membrane Protease (OmpT) Based E. coli Sensing with Anionic Polythiophene and Unlabeled Peptide Substrate

E. coli and Salmonella are two of the most common bacterial pathogens involved in foodborne and waterborne related deaths. Hence, it is critical to develop rapid and sensitive detection strategies for near‐outbreak applications. Reported is a simple and specific assay to detect as low as 1 CFU mL^?1 of E. coli in water within 6 hours by targeting the bacteria's surface protease activity. The assay relies on polythiophene acetic acid (PTAA) as an optical reporter and a short unlabeled peptide (LL37_FRRV) previously optimized as a substrate for OmpT, an outer‐membrane protease on E. coli. LL37_FRRV interacts with PTAA to enhance its fluorescence while also inducing the formation of a helical PTAA‐LL37_FRRV construct, as confirmed by circular dichroism. However, in the presence of E. coli LL37_FRRV is cleaved and can no longer affect the conformations and optical properties of PTAA. This ability to distinguish between an intact and cleaved peptide was investigated in detail using LL37_FRRV sequence variants.     

Carbon Dots Prepared by Hydrothermal Treatment of Dopamine as an Effective Fluorescent Sensing Platform for the Label‐Free Detection of Iron(III) Ions and Dopamine

A facile, economic and green one‐step hydrothermal synthesis route using dopamine as source towards photoluminescent carbon nanoparticles (CNPs) is proposed. The as‐prepared CNPs have an average size about 3.8 nm. The emission spectra of the CNPs are broad, ranging from approximately 380 (purple) to approximately 525 nm (green), depending on the excitation wavelengths. Due to the favorable optical properties, the CNPs can readily enter into A549 cells and has been used for multicolor biolabeling and bioimaging. Most importantly, the as‐prepared CNPs contain distinctive catechol groups on their surfaces. Due to the special response of catechol groups to Fe³⁺ ions, we further demonstrate that such wholly new CNPs can serve as a very effective fluorescent sensing platform for label‐free sensitive and selective detection of Fe³⁺ ions and dopamine with a detection limit as low as 0.32 μM and 68 nM , respectively. The new “mix‐and‐detect” strategy is simple, green, and exhibits high sensitivity and selectivity. The present method was also applied to the determination of Fe³⁺ ions in real water samples and dopamine in human urine and serum samples successfully.     

Isolation of Phenolic Compounds from Raspberry Based on Molecular Imprinting Techniques and Investigation of Their Anti-Alzheimer’s Disease Properties

Alzheimer’s disease is the most common neurodegenerative disease, characterized by memory loss and cognitive dysfunction. Raspberry fruits contain polyphenols which have antioxidant and anti-inflammatory properties. In this study, we used molecular imprinting technology to efficiently isolate phenolic components from the raspberry ethyl acetate extracts. Six phenolic components (ellagic acid, tiliroside, kaempferol-3-o-rutoside, gallic acid, ferulic acid and vanillic acid) were identified by UPLC-Q-TOF-MS analysis. Molecular docking was used to predict the anti-inflammatory effects and anti-Alzheimer’s potential of these isolated compounds, which showed a good binding ability to diseases and related proteins. However, the binding energy and docking fraction of ellagic acid, tiliroside, and kaempferol-3-o-rutoside were better than those of gallic acid, ferulic acid and vanillic acid. Additionally, by studying the effects of these six phenolic components on the LPS-induced secretion of inflammatory mediators in murine microglial (BV2) cells, it was further demonstrated that they were all capable of inhibiting the secretion of NO, IL-6, TNF-α, and IL-1β to a certain extent. However, ellagic acid, tiliroside, and kaempferol-3-o-rutoside have better inhibitory effects compared to others. The results obtained suggest that the phenolic components extracted from ethyl acetate extracts of raspberry by molecularly imprinted polymers have the potential to inhibit the progression of Alzheimer’s disease.     

A Molecular Platform for Multistate Near‐Infrared Electrochromism and Flip‐Flop,Flip‐Flap‐Flop,and Ternary Memory

A diruthenium complex with a redox‐active amine bridge has been designed, synthesized, and studied by single‐crystal X‐ray analysis and DFT and TDDFT calculations. It shows three well‐separated redox processes with exclusive near‐infrared (NIR) absorbance at each redox state. The electropolymerized film of a related vinyl‐functionalized complex displays multistate NIR electrochromism with low operational potential, good contrast ratio, and long retention time. Flip‐flop, flip‐flap‐flop, and ternary memories have been realized by using the obtained film (ca. 15–20 nm thick) with three electrochemical inputs and three NIR optical outputs that each displays three levels of signal intensity.     

Polymer‐based fluoride‐selective chemosensor: Synthesis,sensing property,and its use for the design of molecular‐scale logic devices

A new styryl‐type monomer, 2‐(4‐vinylbenzyloxy)‐1 ‐naphthaldehyde thiosemicarbazone (VNT), was synthesized and then copolymerized with methyl methacrylate (MMA) by reversible addition fragmentation chain transfer polymerization affording a series of poly(MMA‐co‐VNT)s with different functional unit content, predetermined molecular weight, and narrow molecular‐weight distribution. The desired copolymers were structurally confirmed by various spectroscopic characterizations. Colorimetric and fluorescent titration spectra revealed that the copolymers are highly selective toward fluoride anions over other competitive species including Cl^?, Br^?, I^?, H₂PO₄^?, AcO^?, and HSO₄^?. On addition of F^?, a remarkable colorless‐to‐yellow color change is easily observed by naked eyes. The influence of the copolymer composition and molecular weight on its sensing capacity was then carefully investigated. The results showed that higher VNT‐incorporation amount within the copolymer chains leads to higher sensitivity toward F^? ions. Interestingly, the chromogenic process of the polymeric sensor can be switched back and forth by successively adding F^? and HSO₄^? anions into the dimethyl sulfoxide solution of the polymer, which may be represented by a complementary “IMPLICATION/INHIBIT” logic gate at molecular level using both the ions as the chemical inputs. Based on such a reversible and reproducible sensing system, we designed a molecular‐scale sequential information processing circuit displaying “writing–reading–erasing–reading” behavior and “multiwrite” function in the form of binary logic. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Activity‐Based Sensing: A Synthetic Methods Approach for Selective Molecular Imaging and Beyond

Emerging from the origins of supramolecular chemistry and the development of selective chemical receptors that rely on lock‐and‐key binding, activity‐based sensing (ABS)—which utilizes molecular reactivity rather than molecular recognition for analyte detection—has rapidly grown into a distinct field to investigate the production and regulation of chemical species that mediate biological signaling and stress pathways, particularly metal ions and small molecules. Chemical reactions exploit the diverse chemical reactivity of biological species to enable the development of selective and sensitive synthetic methods to decipher their contributions within complex living environments. The broad utility of this reaction‐driven approach facilitates application to imaging platforms ranging from fluorescence, luminescence, photoacoustic, magnetic resonance, and positron emission tomography modalities. ABS methods are also being expanded to other fields, such as drug and materials discovery.