Signaling Recognition Events with Fluorescent Sensors and Switches.

Detection of chemical and biological agents plays a fundamental role in biomedical, forensic and environmental sciences1–4 as well as in anti bioterrorism applications.5–7 The development of highly sensitive, cost effective, miniature sensors is therefore in high demand which requires advanced technology coupled with fundamental knowledge in chemistry, biology and material sciences.8–13

In general, sensors feature two functional components: a recognition element to provide selective/specific binding with the target analytes and a transducer component for signaling the binding event. An efficient sensor relies heavily on these two essential components for the recognition process in terms of response time, signal to noise (S/N) ratio, selectivity and limits of detection (LOD).14,15 Therefore, designing sensors with higher efficacy depends on the development of novel materials to improve both the recognition and transduction processes. Nanomaterials feature unique physicochemical properties that can be of great utility in creating new recognition and transduction processes for chemical and biological sensors15–27 as well as improving the S/N ratio by miniaturization of the sensor elements.28

Gold nanoparticles (AuNPs) possess distinct physical and chemical attributes that make them excellent scaffolds for the fabrication of novel chemical and biological sensors (Figure 1).29–36 First, AuNPs can be synthesized in a straightforward manner and can be made highly stable. Second, they possess unique optoelectronic properties. Third, they provide high surface-to-volume ratio with excellent biocompatibility using appropriate ligands.30 Fourth, these properties of AuNPs can be readily tuned varying their size, shape and the surrounding chemical environment. For example, the binding event between recognition element and the analyte can alter physicochemical properties of transducer AuNPs, such as plasmon resonance absorption, conductivity, redox behavior, etc. that in turn can generate a detectable response signal. Finally, AuNPs offer a suitable platform for multi-functionalization with a wide range of organic or biological ligands for the selective binding and detection of small molecules and biological targets.30–32,36 Each of these attributes of AuNPs has allowed researchers to develop novel sensing strategies with improved sensitivity, stability and selectivity. In the last decade of research, the advent of AuNP as a sensory element provided us a broad spectrum of innovative approaches for the detection of metal ions, small molecules, proteins, nucleic acids, malignant cells, etc. in a rapid and efficient manner.37



Figure 1

Physical properties of AuNPs and schematic illustration of an AuNP-based detection system.



In this current review, we have highlighted the several synthetic routes and properties of AuNPs that make them excellent probes for different sensing strategies. Furthermore, we will discuss various sensing strategies and major advances in the last two decades of research utilizing AuNPs in the detection of variety of target analytes including metal ions, organic molecules, proteins, nucleic acids, and microorganisms.

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Gold nanoparticles in chemical and biological sensing.

The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less

Nonviral Vectors for Gene Delivery

The photoisomerization of azobenzene has been known for almost 75 years but only recently has this process been widely applied to biological systems. The central challenge of how to productively couple the isomerization process to a large functional change in a biomolecule has been met in a number of instances and it appears that effective photocontrol of a large variety of biomolecules may be possible. This critical review summarizes key properties of azobenzene that enable its use as a photoswitch in biological systems and describes strategies for using azobenzene photoswitches to drive functional changes in peptides, proteins, nucleic acids, lipids, and carbohydrates (192 references).

Azobenzene photoswitches for biomolecules.

Dendrimers in Supramolecular Chemistry: From Molecular Recognition to Self-Assembly.

As novel calixarene or macrocyclic types of extractants, 37, 38, 39, 40, 41, 42-hexakis(carboxymethoxy)-5, 11, 17, 23, 29, 35-hexakis(1, 1, 3, 3-tetramethylbutyl)calix[6]arene and 25, 26, 27, 28-tetrakis(carboxymethoxy)-5, 11, 17, 23-tetrakis(1, 1, 3, 3- tetramethylbutyl)calix[4]arene as well as p-(1, 1, 3, 3-tetramethylbutyl)phenoxy acetic acid, as their monomeric analog, and 2, 6-bis[2-carboxymethoxy-5-(1, 1, 3, 3-tetramethylbutyl)benzyl]-4-(1, 1, 3, 3-tetramethylbutyl)phenoxyacetic acid as a linear trimer analog, have been synthesized in order to investigate their extraction abilities of rare earth metal ions, RE3+ (RE=Y, La, Pr, Nd, Sm, Eu, Gd, Ho, Er), from an aqueous nitrate solution. It was found that the calixarene derivatives provide much higher extractability and greater separation efficiency than do the monomeric analog and the other acidic carboxylate extractants. The selectivity for rare earth elements in this system is not affected by the ring size. In extraction from an aqueous mixture of nitric acid-glycine, the stoichiometry of the extracted species was determined and the extraction equilibrium constants as well as the separation factors were evaluated for each extractant. A stripping test was also performed and the stripping of rare earths was found to be successfully achieved with diluted hydrochloric acid.

/pdf/solvent-extraction-of-trivalent-rare-earth-metal-ions-with-2v7xdi5ic7.pdf

Solvent Extraction of Trivalent Rare Earth Metal Ions with Carboxylate Derivatives of Calixarenes

Water-soluble fullerenes have attracted attention as promising compounds that have been used to forge new paths in the field of photo-biochemistry. To prepare water-soluble fullerenes, we employed lipid-membrane-incorporated fullerenes (LMICx; x=60 or 70) by using the fullerene exchange method from a gamma-cyclodextrin (gamma-CD) cavity to vesicles. LMIC60 have low toxicity in the dark and engender cell death by photoirradiation (lambda>350 nm). Furthermore, the photodynamic activity of LMIC70 is 4.7-fold that of LMIC60 for the same photon flux (lambda>400 nm). One of the reasons for the higher phototoxicity of LMIC70 is the higher generation of singlet oxygen (1O2) in LMIC70 than in LMIC60. The difference between LMIC60 and LMIC70 is considered to be simply derived from the amount of light absorption in the 400-700 nm region that is suitable for photodynamic therapy (PDT). To the best of our knowledge, this is the first case in which biological activity of C70 and its derivatives toward HeLa cells has been assayed.

Intracellular Uptake and Photodynamic Activity of Water‐Soluble [60]‐ and [70]Fullerenes Incorporated in Liposomes

The organization of lateral domains, called lipid rafts, in plasma membranes is essential for physiological functions, such as signaling and trafficking. In this study, we performed a systematic analysis of lateral phase separation under membrane tension. We applied osmotic pressure directed toward the outside of vesicles to induce membrane tension. Microscopic observations clarified the shifts in phase structures within bilayer membranes with change in tension and temperature. The miscibility transition temperature between one-liquid and two-liquid states was shown to increase under tension. We also observed a shift in the transition temperature between two-liquid and solid–liquid states in membranes under tension. We determined a quantitative phase diagram of phase organization with respect to the applied pressure and temperature. The results indicate that membrane tension can induce phase separation in homogeneous membranes. Our findings may provide insight into the biophysics of bilayer phase organization under tension, which is an intrinsic mechanical property of membranes.

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Lateral phase separation in tense membranes

Host—Guest Properties of New Water-Soluble Calixarenes Derived from p-(Chloromethyl)calixarenes

We have developed a method for the photomanipulation of lipid membrane morphology in which the shape of a vesicle can be switched by light through the use of a synthetic photosensitive amphiphile containing an azobenzene unit (KAON12). We prepared cell-sized liposomes from KAON12 and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and conducted real-time observations of vesicular transformation in the photosensitive liposome by phase-contrast microscopy. Budding transitions-either budding toward the centre of the liposome (endo-bud) or budding out of the liposome (exo-bud)-could be controlled by light. We discuss the mechanism of this transformation in terms of the change in the effective membrane surface area due to photoisomerization of the constituent molecules.

Takeshi Nagasaki

Papers

Solvent Extraction of Trivalent Rare Earth Metal Ions with Carboxylate Derivatives of Calixarenes

Intracellular Uptake and Photodynamic Activity of Water‐Soluble [60]‐ and [70]Fullerenes Incorporated in Liposomes

Lateral phase separation in tense membranes

Host—Guest Properties of New Water-Soluble Calixarenes Derived from p-(Chloromethyl)calixarenes

Reversible Control of Exo- and Endo-Budding Transitions in a Photosensitive Lipid Membrane