Intermolecular communication on a liposomal membrane: enzymatic amplification of a photonic signal with a gemini peptide lipid as a membrane-bound artificial receptor

A supramolecular system that can activate an enzyme through photo-isomerization was constructed by using a liposomal membrane scaffold. The design of the system was inspired by natural signal transduction systems, in which enzymes amplify external signals to control signal transduction pathways. The liposomal membrane, which provided a scaffold for the system, was prepared by self-assembly of a photoresponsive receptor and a cationic synthetic lipid. NADH-dependent L-lactate dehydrogenase, the signal amplifier, was immobilized on the liposomal surface by electrostatic interactions. Recognition of photonic signals by the membrane-bound receptor induced photo-isomerization, which significantly altered the receptor's metal-binding affinity. The response to the photonic signal was transmitted to the enzyme by Cu(2+) ions. The enzyme amplified the chemical information through a catalytic reaction to generate the intended output signal.     

Switching of the enzymatic activity synchronized with signal recognition by an artificial DNA receptor on a liposomal membrane

We constructed a supramolecular system on a liposomal membrane that is capable of activating an enzyme via DNA hybridization. The design of the system was inspired by natural signal transduction systems, in which enzymes amplify external signals to control signal transduction pathways. The liposomal membrane, providing a platform for the system, was prepared by the self-assembly of an oligonucleotide lipid, a phospholipid and a cationic synthetic lipid. The enzyme was immobilized on the liposomal surface through electrostatic interactions. Selective recognition of DNA signals was achieved by hybridizing the DNA signals with the oligonucleotide lipid embedded in the liposome. The hybridized DNA signal was sent to the enzyme by a copper ion acting as a mediator species. The enzyme then amplified the event by the catalytic reaction to generate the output signal. In addition, our system demonstrated potential for the discrimination of single nucleotide polymorphisms.     

囊泡表面分子间通讯交流体系的构建: 利用受体的分子识别行为调控酶的活性

在人工双层膜囊泡表面, 构建了一个通过人工受体的分子识别行为控制酶反应活性的超分子体系. 体系以生物体细胞信号转导系统为模拟原型, 由作为受体的烷基胺、被受体识别的信号分子吡哆醛衍生物、乳酸脱氢酶、受体和酶之间的媒介物Cu^2＋以及作为体系载体的合成肽脂囊泡五个成分构成．通过UV-vis光谱法及动态光散射测定对体系进行了评价, 结果表明: 随着受体疏水参数增大, 其对信号分子的识别能力增强, 二者呈良好的线性关系; 通过信号分子与囊泡表面静电相互作用的研究表明信号分子具有选择性; 媒介物与信号分子–受体可形成化学计量比为1∶2的配合物, 其形成能力比媒介物与酶的结合能力更强．作为结论, 体系中烷基胺受体对磷酸吡哆醛信号分子的识别有效控制了处于囊泡表面的乳酸脱氢酶的活性．     

Enhanced Anticancer Efficacy by ATP‐Mediated Liposomal Drug Delivery

A liposome‐based co‐delivery system composed of a fusogenic liposome encapsulating ATP‐responsive elements with chemotherapeutics and a liposome containing ATP was developed for ATP‐mediated drug release triggered by liposomal fusion. The fusogenic liposome had a protein–DNA complex core containing an ATP‐responsive DNA scaffold with doxorubicin (DOX) and could release DOX through a conformational change from the duplex to the aptamer/ATP complex in the presence of ATP. A cell‐penetrating peptide‐modified fusogenic liposomal membrane was coated on the core, which had an acid‐triggered fusogenic potential with the ATP‐loaded liposomes or endosomes/lysosomes. Directly delivering extrinsic liposomal ATP promoted the drug release from the fusogenic liposome in the acidic intracellular compartments upon a pH‐sensitive membrane fusion and anticancer efficacy was enhanced both in vitro and in vivo.     

Signal‐responsive gating of porous membranes by polymer brushes

Various types of signal‐responsive polymers were grafted on surfaces of porous membranes as polymer brushes. The grafted polymers shrank and extended in response to environmental signals, such as pH, ionic strength, temperature, redox reaction and photo‐irradiation. The pore size was regulated by the extent of the polymer brush. The phenomenon was observed in situ by atomic force microscopy. As a result, the substance permeation through the porous membrane was controlled in response to the signals. The permeation control was rapid in comparison with hygrogel‐type membranes, and was reversibly performed. Copyright © 2000 John Wiley & Sons, Ltd.     

Spiropyran‐Conjugated Pluronic as a Dual Responsive Colorimetric Detector

Novel spiropyran‐conjugated Pluronic [polyethylene oxide (PEO)‐b‐polypropylene oxide (PPO)‐b‐polyethylene oxide (PEO)] micelles are developed as a new colorimetric detector showing photo‐ or thermo‐switchable behavior. Facile conjugation of spiropyran to Pluronic was confirmed by ¹H NMR, UV–Vis, and Fluorescence spectroscopy. A switchable photoluminescence is found depending on the irradiation with either UV or visible light, and temperature resulting from structural isomerization of spiropyran between spiropyran (SP) and merocyanine (MC) form. Cytotoxicity of the spiropyran‐conjugated Pluronic (SP‐PL) was evaluated following an MTT assay, whereas photo responsiveness of spiropyran within the micelles was determined by confocal laser scanning microscopy.     

Inter-Vesicle Signal Transduction Using a Photo-Responsive Zinc Ionophore

Transmission of chemical information between cells and across lipid bilayer membranes is of profound significance in many biological processes. The design of synthetic signalling systems is a critical step towards preparing artificial cells with collective behaviour. Here, we report the first example of a synthetic inter-vesicle signalling system, in which diffusible chemical signals trigger transmembrane ion transport in a manner reminiscent of signalling pathways in biology. The system is derived from novel ortho-nitrobenzyl and BODIPY photo-caged Zn^II transporters, in which cation transport is triggered by photo-decaging with UV or red light, respectively. This decaging reaction can be used to trigger the release of the cationophores from a small population of sender vesicles. This in turn triggers the transport of ions across the membrane of a larger population of receiver vesicles, but not across the sender vesicle membrane, leading to overall inter-vesicle signal transduction and amplification.     

A D‐Peptide Ligand of Nicotine Acetylcholine Receptors for Brain‐Targeted Drug Delivery

Lysosomes of brain capillary endothelial cells are implicated in nicotine acetylcholine receptor (nAChR)‐mediated transcytosis and act as an enzymatic barrier for the transport of peptide ligands to the brain. A D ‐peptide ligand of nAChRs (termed ^DCDX), which binds to nAChRs with an IC₅₀ value of 84.5 nM , was developed by retro–inverso isomerization. ^DCDX displayed exceptional stability in lysosomal homogenate and serum, and demonstrated significantly higher transcytosis efficiency in an in vitro blood–brain barrier monolayer compared with the parent L ‐peptide. When modified on liposomal surface, ^DCDX facilitated significant brain‐targeted delivery of liposomes. As a result, brain‐targeted delivery of ^DCDX modified liposomes enhanced therapeutic efficiency of encapsulated doxorubicin for glioblastoma. This study illustrates the importance of ligand stability in nAChRs‐mediated transcytosis, and paves the way for developing stable brain‐targeted entities.     

A Sensitive Electrochemical Immunosensor for α‐Fetoprotein Detection with Colloidal Gold‐Based Dentritical Enzyme Complex Amplification

A sensitive and specific electrochemical immunosensor was developed with α‐fetoprotein (AFP) as the model analyte by using gold nanoparticle label for enzymatic catalytic amplification. A self‐assembled monolayer membrane of mercaptopropionic acid (MPA) was firstly formed on the electrode surface through gold‐sulfur interaction. Monoclonal mouse anti‐human AFP was covalently immobilized to serve as the capture antibody. In the presence of the target human AFP, gold nanoparticles coated with polyclonal rabbit anti‐human AFP were bound to the electrode via the formation of a sandwiched complex. With the introduction of goat anti‐rabbit IgG conjugated with alkaline phosphatase, the dentritical enzyme complex was formed through selective interaction of the secondary antibodies with the colloidal gold‐based primary antibody at the electrode, thus affording the possibility of signal amplification for AFP detection. Current response arising from the oxidation of enzymatic product was significantly amplified by the dentritical enzyme complex. The current signal was proportional to the concentration of AFP from 1.0 ng mL^?1 to 500 ng mL^?1 with a detection limit of 0.8 ng mL^?1. This system could be extended to detect other target molecules with the corresponding antibody pairs.     

Artificial Signal Transduction with Primary and Secondary Messengers

The complete, entirely artificial, signal‐transduction process was realized with a pair of tailored transmembrane units that were equipped with receptor‐ and reactive sites at both amphiphilic ends. Thus, docking of the primary messenger, transmission of the signal, and release of the secondary messenger could all be imitated in a single experimental setup. The system imitates the signaling principle of receptor tyrosine kinases and employs bisphosphonate head‐groups for oligoamine‐recognition and a pair of thiol nucleophiles and pyridine disulfide tail‐groups for intravesicle S_N2 displacement. This system operates in a unidirectional fashion, does not suffer from intervesicle competition, and is highly sensitive towards the lipid composition of the membrane and the nature of the primary messenger.     

Biometallization‐Based Electrochemical Magnetoimmunosensing Strategy for Avian Influenza A (H7N9) Virus Particle Detection

A highly sensitive electrochemical immunosensor for avian influenza A (H7N9) virus (H7N9 AIV) detection was proposed by using electrochemical magnetoimmunoassay coupled with biometallization and anodic stripping voltammetry. This strategy could accumulate the enzyme‐generated product on the surface of the magneto electrode by means of silver deposition, which amplified the detection signal about 80 times. The use of magnetic beads (MBs) and the magneto electrode could also amplify the detection signal. Furthermore, a bi‐electrode signal transduction system was introduced into this immunosensor, which is also beneficial to the immunoassay. A concentration as low as 0.011 ng mL^?1 of H7N9 AIV could be detected in about 1.5 h with good specificity. This study not only provides a simple and sensitive approach for virus detection but also offers an effective signal enhancement strategy for the development of highly sensitive MB‐based electrochemical immunoassays.     

Tunable Supramolecular Assembly and Photoswitchable Conversion of Cyclodextrin/Diphenylalanine‐Based 1D and 2D Nanostructures

A photocontrolled, interconvertible supramolecular 2D‐nanosheet/1D‐nanotube system was constructed through the supramolecular assembly of adamantanyl‐modified diphenylalanine with azobenzene‐bridged bis(β‐cyclodextrin). The nanosheet exhibited a greater fluorescence enhancement effect than the nanotube. Significantly, these nanosheets and nanotubes could interconvert via the photocontrolled trans/cis isomerization of azobenzene linkers in bis(β‐cyclodextrin), and this photo‐switchable one‐dimensional/two‐dimensional morphological interconversion was reversible and recyclable. This enables convenient routes to highly ordered nanostructures with various morphologies and dimensions that can be controlled by external stimuli.     

The Regulation of the Calcium Signal by Membrane Pumps

Calcium may have a static, structure‐stabilizing role in biological organs like the bones and the teeth, or may fulfill a dynamic function in cells as a regulator of signal‐transduction pathways. This is made possible by the properties of the Ca²⁺ ion (e.g., high dehydration rate, great flexibility in coordinating ligands, largely irregular geometry of the coordination sphere). Since Ca²⁺ is a universal carrier of signals, the control of its homeostasis is of central importance for the organism. It involves exchanges between the skeleton (which is the major calcium reservoir) and the extracellular and intracellular fluids. It also involves the intestine and the kidney, the organs of Ca absorption and release, respectively. The highly integrated homeostasis process consists of a number of hormonally controlled feedback loops, and an elaborate system of membrane channels, exchangers, and pumps that control the Ca²⁺ flux into and out of cells.     

Phase-dependent photochromism of a lactone-stabilized chromene from a flavylium reaction network

New trans‐2‐hydroxychalcones bearing a carboxylate group at position 2′ ( Ct ^?) were synthesized (compounds 2 and 3 ). These compounds lead to a network of chemical reactions depending on pH value, light, and solvent. In water, when the pH value is lowered, the ionized trans‐chalcone is protonated and the flavylium cation A H⁺ is formed at very acidic pH values through hemiketal B and cis‐chalcone Cc , with global acidity constants of pK′_a ≤?1 and ≈0.1, respectively, for 2 and 3 . The electron‐acceptor character of the carboxylic substituent not only increases the observed acidity of the flavylium cation, but also decreases the rate of the ring‐opening/‐closing from a subsecond timescale to hours relative to model compound 1 (without carboxylate). The photochemistry of the network was studied in detail by means of continuous irradiation, monitored by UV/Vis absorption and ¹H and ¹³C NMR spectroscopic analysis. Although compound 3 is only slightly photoactive, compound 2 ( Ct^? ) reacts in aqueous solutions (λ_irr=313 nm) to form B^? and Cc^? , with a global quantum yield of 0.15, and fully reverts back to Ct^? with a rate constant of k=6.7×10^?5 s^?1. The flavylium cation is no longer formed in methanol, and irradiation of Ct^? leads to the formation of B ^? and the new lactone‐trapped chromene species La . The formation of La takes place through a sequence of three photochemical steps: photoisomerization of Ct ^?, photo‐ring‐closing reaction of Cc ^?, and photolactonization of B ^?. Only the cis/trans isomerization and ring‐closing reactions are thermally reversible on a timescale of seconds and hours, respectively. A photochromic system was achieved in rigid matrices of methanol (at 77 K) and 1‐dodecanol (5 °C) by irradiating lactone La to give a red ortho‐quinone allide through a photo‐ring‐opening reaction; the color disappears with a rate constant of k=1.25×10^?2 s^?1 in 1‐dodecanol at 5 °C.     

Tetrathiafulvalene?Benzothiadiazoles as Redox‐Tunable Donor–Acceptor Systems: Synthesis and Photophysical Study

Electrochemical and photophysical analysis of new donor–acceptor systems 2 and 3 , in which a benzothiadiazole (BTD) unit is covalently linked to a tetrathiafulvalene (TTF) core, have verified that the lowest excited state can be ascribed to an intramolecular‐charge‐transfer (ICT) π(TTF)→π*(benzothiadiazole) transition. Owing to better overlap of the HOMO and LUMO in the fused scaffold of compound 3 , the intensity of the ¹ICT band is substantially higher compared to that in compound 2 . The corresponding CT fluorescence is also observed in both cases. The radical cation TTF^+. is easily observed through chemical and electrochemical oxidation by performing steady‐state absorption experiments. Interestingly, compound 2 is photo‐oxidized under aerobic conditions.     

Polarity‐Dependent Isomerization of an Unsymmetrical Overcrowded Ethylene Promoted by Zwitterionic Contribution in the Twisted Isomer

The twisted form of bianthrone is known as a metastable state provided by a photo‐induced or thermal‐induced isomerization of the folded form, and thus prevents the isolation and the detailed analysis of its electronic structure. In this study, an unsymmetrical bianthrone ( 2 ), consisting of the electron‐withdrawing anthrone and electron‐donating acridane, have been synthesized and shown to exhibit a solvent‐polarity‐dependent isomerization reaction between the folded and twisted isomers. With increasing the polarity of the solvent, 2 showed an isomerization reaction from the folded form to the twisted form. The stabilization of the twisted isomer in polar solvents can be interpreted as proof of its relatively large zwitterionic character. The DMF solution of 2 displayed paramagnetically‐broadened NMR signals from the thermally populated triplet state resulting from rotation of the weakened ethylenic double bond of the twisted isomer.     

Total Synthesis of Farnesin through an Excited‐State Nazarov Reaction

The asymmetric total synthesis of farnesin, a rearranged ent‐kaurenoid, was achieved through a convergent approach involving photo‐Nazarov and intramolecular aldol cyclizations to build the syn‐syn‐syn hydrofluorenol ABC ring system and bicyclo[3.2.1]octane CD ring system in the first application of a UV‐light‐induced excited‐state Nazarov cyclization of a non‐aromatic dicyclic divinyl ketone in a total synthesis. Unlike the conventional acid‐promoted ground‐state Nazarov reaction, the excited‐state Nazarov reaction enables stereospecific formation of the highly strained syn‐syn‐syn‐fused hydrofluorenone scaffold through a disrotatory cyclization.     

Laser emission in a 3D nanoporous polymer replica of amorphous blue phase III

Wide‐temperature polymer stabilized cubic blue phases (BPI and BPII) facilitated the emergence of practically feasible band‐edge BP lasers. However, the mysterious “blue fog” amorphous BPIII always remained elusive in terms of its applicability to photonic devices due to its random amorphous structure devoid of photonic bandgaps and due to the difficulty in effectively identifying and stabilizing it for practical applications. We present the first photonic device based on amorphous BPIII by demonstrating that a three‐dimensional BPIII polymer scaffold or template, when infiltrated with liquid crystal and laser dye, forms a system where random lasing action is generated due to multiple scattering events occurring in the nanoporous and disordered polymer replica of BPIII. This study represents a facile approach for the development of photonic devices which favorably exploit unique polymer network morphologies for laser emission. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 551–557     

Dual Signal Amplification Electrochemical Biosensor for Lead Cation

Herein, a sensitive electrochemical Pb²⁺ sensor was developed which based on DNA‐functionalized Au nanoparticles(AuNPs) and nanocomposite modified electrode. The DNA‐functionalized AuNPs includes two types of DNA, namely a Pb²⁺‐mediated DNAzyme comprising a biotin labeled‐enzyme DNA and a substrate strand DNA with a typical stem‐loop structure, and a ferrocene‐labeled linear signal DNA. Without Pb²⁺, the hairpin loop impeded biotin binding to avidin on the electrode. However,when the goal Pb²⁺ exists, the substratum strand was divided into two fragments that lead to the enzyme strand was substratumed on the electrode and biotin was admited by avidin, bringing about DNA‐functionalized AuNP(AuNPs) deposition on the electrode surface.The differential pulse voltammetry (DPV) was used to measure electrochemical response signals connect to signal DNA.For the amplification characters of the DNA‐functionalized AuNPs and nanocomposite, the electrochemical detection signal of Pb²⁺ was greatly improved and revealed high specificity. Under optimum conditions, the resultant biosensor bringed out a high sensitivity and selectivity for the determination of Pb²⁺. The proposed method was able to detect as low as picomolar Pb²⁺ concentrations.     

Dynamic Inversion of Stereoselective Phosphate Binding to a Bisurea Receptor Controlled by Light and Heat

A chiral bisurea anion receptor, derived from a first‐generation molecular motor, can undergo photochemical and thermal isomerization operating as a reconfigurable system. The two possible cis configurations in the isomerization cycle are opposite in helicity, as is shown by CD spectroscopy. ¹H NMR titrations demonstrate that the P and M helical cis isomers hold opposite enantioselectivity in the binding of binol phosphate, while anion complexation by the intermediate trans isomer is not selective. The difference in the binding affinity of the enantiomers was rationalized by DFT calculations, revealing very distinct binding modes. Thus, the enantiopreferred substrate binding in this receptor can be inverted in a dynamic fashion using light and heat.