Bioinspired artificial photonic nanoarchitecture using the elytron of the beetle Trigonophorus rothschildi varians as a 'blueprint'.

An unusual, intercalated photonic nanoarchitecture was discovered in the elytra of Taiwanese Trigonophorus rothschildi varians beetles. It consists of a multilayer structure intercalated with a random distribution of cylindrical holes normal to the plane of the multilayer. The nanoarchitectures were characterized structurally by scanning electron microscopy and optically by normal incidence, integrated and goniometric reflectance measurements. They exhibit an unsaturated specular and saturated non-specular component of the reflected light. Bioinspired, artificial nanoarchitectures of similar structure and with similar properties were realized by drilling holes of submicron size in a multilayer structure, showing that such photonic nanoarchitectures of biological origin may constitute valuable blueprints for artificial photonic materials.

Optical near-field excitations on plasmonic nanoparticle-based structures.

We investigate optical excitations on single silver nanospheres and nanosphere composites with the Finite Difference Time Domain (FDTD) method. Our objective is to achieve polarization control of the enhanced local field, pertinent to SERS applications. We employ dimer and quadrumer structures, which can display broadband and highly confined near-field-intensity enhancement comparable to or exceeding the resonant value of smaller sized isolated spheres. Our results demonstrate that the polarization of the enhanced field can be controlled by the orientation of the multimers in respect to the illumination, rather than the illumination itself. In particular, we report cases where the enhanced field shares the same polarization with the exciting field, and cases where it is predominantly perpendicular to the source field. We call the later phenomenon depolarized enhancement. Furthermore, we study a realizable nanolens based on a tapered self-similar silver nanosphere array. The time evolution of the fields in such structures show conversion of a diffraction limited Gaussian beam to a focused spot, through sequential coupling of the nano-array spheres' Mie-plasmons. For a longitudinally excited nanolens design we observed the formation of an isolated focus with size about one tenth the vacuum wavelength. We believe such nanolens will aid scanning near-field optical microscopy (SNOM) detection and the excitation of surface plasmon based guiding devices.

Wing scale microstructures and nanostructures in butterflies--natural photonic crystals.

The aim of our study was to investigate the correlation between structural colour and scale morphology in butterflies. Detailed correlations between blue colour and structure were investigated in three lycaenid subfamilies, which represent a monophylum in the butterfly family Lycaenidae (Lepidoptera): the Coppers (Lycaeninae), the Hairstreaks (Theclinae) and the Blues (Polyommatinae). Complex investigations such as spectral measurements and characterization by means of light microscopy, scanning electron microscopy and transmission electron microscopy enabled us to demonstrate that: (i) a wide array of nanostructures generate blue colours; (ii) monophyletic groups use qualitatively similar structures; and (iii) the hue of the blue colour is characteristic for the microstructure and nanostructure of the body of the scales.

Color-selecting reflectors inspired from biological periodic multilayer structures.

We propose a semi-infinite 1-D photonic crystal approach for designing artificial reflectors which aim to reproduce color changes with the angle of incidence found in biological periodic multilayer templates. We show that both the dominant reflected wavelength and the photonic bandgap can be predicted and that these predictions agree with exact calculations of reflectance spectra for a finite multilayer structure. In order to help the designer, the concept of spectral richness of angle-tuned color-selecting reflectors is introduced and color changes with angle are displayed in a chromaticity diagram. The usefulness of the photonic crystal approach is demonstrated by modelling a biological template (found in the cuticle of Chrysochora vittata beetle) and by designing a bio-inspired artificial reflector which reproduces the visual aspect of the template. The bioinspired novel aspect of the design relies on the strong unbalance between the thicknesses of the two layers forming the unit cell.

The design of cationic lipids for gene delivery.

Synthetic gene delivery vectors are gaining increasing importance in gene therapy as an alternative to recombinant viruses. Among the various types of non-viral vectors, cationic lipids are especially attractive as they can be prepared with relative ease and extensively characterised. Further, each of their constituent parts can be modified, thereby facilitating the elucidation of structure-activity relationships. In this forward-looking review, cationic lipid-mediated gene delivery will mainly be discussed in terms of the structure of the three basic constituent parts of any cationic lipid: the polar headgroup, hydrophobic moiety and linker. Particular emphasis will be placed on recent advances in the field as well as on our own original contributions. In addition to reviewing critical physicochemical features (such as headgroup hydration) of monovalent lipids, the use of headgroups with known nucleic-acid binding modes, such as linear and branched polyamines, aminoglycosides and guanidinium functions, will be comprehensively assessed. A particularly exciting innovation in linker design is the incorporation of environment-sensitive groups, the intracellular hydrolysis of which may lead to more controlled DNA delivery. Examples of pH-, redox- and enzyme-sensitive functional groups integrated into the linker are highlighted and the benefits of such degradable vectors can be evaluated in terms of transfection efficiency and cationic lipid-associated cytotoxicity. Finally, possible correlations between the length and type of hydrophobic moiety and transfection efficiency will be discussed. In conclusion it may be foreseen that in order to be successful, the future of cationic lipid-based gene delivery will probably require the development of sophisticated virus-like systems, which can be viewed as "programmed supramolecular systems" incorporating the various functions required to perform in a chronological order the different steps involved in gene transfection.

Band structure and omnidirectional photonic band gap in lamellar structures with left-handed materials.

We theoretically investigate the photonic band structure of one-dimensional superlattices composed of alternating layers of right-handed and left-handed materials (RHM and LHM). The dispersion curves are mainly studied by assuming that the dielectric permittivity and magnetic permeability are constant in each layer. It is shown that such structures can exhibit new types of electromagnetic modes and dispersion curves that do not exist in usual superlattices composed only of RHM. In particular, we emphasize the possibility of bands that originate from the interface modes localized at the boundary between a LHM and RHM or from confined modes in one type of layers. These waves are evanescent in both or in one constituent of the superlattice. One of the pass bands may lie below the light lines of the constituting material and go down to the static limit of a vanishing frequency omega, even at a value of the wave vector k(//) (parallel to the layers) that is different from zero. For a given value of the wave vector k(//), the dispersion curves omega versus k(z) (where k(z) is the Bloch wave vector of the periodic system along the axis of the superlattice) may exist only in a limited part of the superlattice Brillouin zone and exhibit a zigzag behavior instead of a monotonic behavior as in usual superlattices. With an appropriate choice of the parameters, we show that it is possible to realize an absolute (or omnidirectional) band gap for either transverse electric (TE) or transverse magnetic (TM) polarization of the electromagnetic waves. A combination of two multilayer structures composed of RHM and LHM is proposed to realize, in a certain range of frequency, an omnidirectional reflector of light for both polarizations.

Simple nanometric plasmon multiplexer.

We present a simple multiplexing structure made of two discrete plasmon wires coupled by two metal nanoclusters. We show that this simple nanosystem can transfer one plasmon wavelength from one wire to the other. Closed-form relations between the transmission coefficients and the nanocluster distances are given to optimize the desired directional plasmon ejection.

Role of photonic-crystal-type structures in the thermal regulation of a Lycaenid butterfly sister species pair.

One of the possible functions of the photonic-crystal structure found on the wing scales of some butterflies is investigated. The optical and electron microscopic investigation of two male butterflies-blue (colored) and brown (discolored)-representing a sister species pair and originating from different altitudes, revealed that the blue color can be attributed unambiguously to the fine, spongelike medium, called "pepper-pot structure," present between the ridges and the cross ribs in the scales of the colored butterfly. Only traces of this structure can be found on the scales of the discolored butterfly. Other physical measurements, mainly optical reflectivity, transmission, and thermal measurements, are correlated with structural data and simulation results. The thermal measurements reveal that under identical illumination conditions the high-altitude butterfly reaches a temperature 1.3-1.5 times the temperature reached by the low-altitude butterfly. This is attributed to the photonic-crystal-like behavior of the pepper-pot structure, which significantly reduces the penetration of light with wavelength in the blue region of the spectrum into the body of the scales. This sheds some light on the adaptation that enhances the survival chance of the butterfly in a cold environment rich in blue and UV radiation.

Sterically stabilized BGTC-based lipoplexes: structural features and gene transfection into the mouse airways in vivo.

BACKGROUND: Colloidal stability of lipid/DNA aggregates is a major requirement for cationic lipid-mediated transfection which is particularly difficult to fulfil at the high DNA concentrations used for in vivo gene delivery. Thus, we have investigated the potential of poly(ethyleneglycol) (PEG) conjugates for steric stabilization of lipoplexes formed by bis(guanidinium)-tren-cholesterol/dioleoyl phosphatidylethanolamine (BGTC/DOPE) liposomes, a class of cationic liposomes we have developed over the past few years. METHODS AND RESULTS: We demonstrate that adequate lipophilic PEG derivatives can stabilize BGTC/DOPE lipoplexes formed at high DNA concentration. We also report the results of cryotransmission electron microscopy studies indicating that PEG-stabilized lipoplexes form DNA-coated structures which assemble into clusters exhibiting various complex morphologies. Finally, we report data from in vivo transfection experiments suggesting that PEG-mediated colloidal stabilization of concentrated lipoplex solutions may allow enhanced transfection of the mouse airways via intranasal administration. CONCLUSION: Our results represent an important step towards the design of multimodular BGTC-based systems for improved in vivo gene transfection.

Direct photocleavage of HIV-DNA by quinacridine derivatives triggered by triplex formation.

Amino-p-quinacridine compounds (PQs) have been shown to stabilize strongly and specifically triple-helical DNA. Moreover, these derivatives display photoactive properties that make them efficient DNA cleavage agents. We exploited these two properties (triplex-specific binding and photoactivity) to selectively cleave a double-stranded (ds)DNA sequence present in the HIV-1 genome. Cleavage was first carried out on a linearized plasmid (3300 bp) containing the HIV polypurine tract (PPT) that allowed targeting by a triplex-forming oligonucleotide (TFO). PQ(3)(), the most active compound of the series, efficiently cleaved double-stranded DNA in the vicinity of the PPT when this sequence had formed a triplex with a 16-mer TFO. Investigation of the cleavage at the molecular level was addressed on a short DNA fragment (56 bp); the photoinduced cleavage by PQ(3)() occurred only in the presence of the triple helix. Nevertheless, unusual cleavage patterns were observed: damage was observed at guanines located 6-9 bp away from the end of the triple helical site. This cleavage is very efficient (up to 60%), does not require alkaline treatment, and is observed on both strands. A quinacridine-TFO conjugate produced the same cleavage pattern. This observation, along with others, excludes the hypothesis of a triplex-induced allosteric binding site of PQ(3 )()adjacent to the damaged sequence and indicates that PQ(3 )()preferentially binds in the vicinity of the 5'-triplex junction. Irradiation in the presence of TFO-conjugates with acridine (an intercalative agent) and with the tripeptide lys-tryp-lys led to a complete inhibition of the photocleavage reaction. These results are interpreted in terms of competitive binding and of electron-transfer quenching. Together with the findings of simple mechanistic investigations, they led to the conclusion that the photoinduced damage proceeds through a direct electron transfer between the quinacridine and the guanines. This study addresses the chemical mechanism leading to strand breakage and characterizes the particular photosensitivity of the HIV-DNA target sequence which could be an oxidative hot spot for addressed photoinduced strand scission by photosensitizers.

Human DNA topoisomerase I inhibitory activities of synthetic polyamines: relation to DNA aggregation.

DNA aggregation by polyamines has acquired importance as a prerequisite for the cellular uptake of DNA for gene therapy. Intracellular polyamines are constitutive components of mammalian cells and their availability is critical for cell proliferation. Interference of polyamine biosynthesis by synthetic polyamines leads to cytotoxicity. Optimization of the polyamine structural parameters is necessary to control their DNA aggregation, cytotoxic or enzyme inhibitory activities. We designed two series of tetra- and hexamines and compared their human DNA topoisomerase I (top1) inhibitory effects with the DNA aggregation properties. We show that hexamines are more efficient inhibitors of DNA relaxation by top1 than tetramines and that they suppress the top1-mediated DNA cleavage while tetramines do not. The DNA aggregation abilities within two series of polyamines correlate with the length of their central methylene chain. By contrast, the top1 inhibition within two series does not show the same correlation but demonstrates a threshold inhibitory effect on going from the (CH(2))(12) to the (CH(2))(14) central chain. We show further that the structures of DNA aggregates formed by polyamines with the (CH(2))(10-12) or with the (CH(2))(14-16) chains are very different. The first are a fluid cholesteric-type phases, whereas the second are well-structured aggregates similar to columnar liquid crystals with high packing density of DNA duplexes. The structures of polyamines-induced DNA aggregates are proposed to be crucial for top1 catalysis. The structure-function correlation described here may serve as a guide for rational design of polyamines with desired DNA-aggregation or anti-top1 activities.

Self-consistent photonic band structure of dielectric superlattices containing nonlinear optical materials.

The theory of photonic crystals is extended to include the optical Kerr effect taking place in weak third-order, nonlinear materials present in the unit cell. The influence on the dispersion relations of the illumination caused by a single Bloch mode transiting through the crystal structure is examined. Special attention is given to the modification of the photonic gap width and position. Assuming an instantaneous change of refractive index with illumination, the nonlinear band structure problem is solved as a sequence of ordinary, linear band structure calculations, carried out in a plane-wave field representation.

Telomerase inhibitors based on quadruplex ligands selected by a fluorescence assay.

The reactivation of telomerase activity in most cancer cells supports the concept that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to inhibit telomerase activity. We used a fluorescence assay to identify molecules that stabilize G-quadruplexes. Intramolecular folding of an oligonucleotide with four repeats of the human telomeric sequence into a G-quadruplex structure led to fluorescence excitation energy transfer between a donor (fluorescein) and an acceptor (tetramethylrhodamine) covalently attached to the 5' and 3' ends of the oligonucleotide, respectively. The melting of the G-quadruplex was monitored in the presence of putative G-quadruplex-binding molecules by measuring the fluorescence emission of the donor. A series of compounds (pentacyclic crescent-shaped dibenzophenanthroline derivatives) was shown to increase the melting temperature of the G-quadruplex by 2-20 degrees C at 1 microM dye concentration. This increase in T(m) value was well correlated with an increase in the efficiency of telomerase inhibition in vitro. The best telomerase inhibitor showed an IC(50) value of 28 nM in a standard telomerase repeat amplification protocol assay. Fluorescence energy transfer can thus be used to reveal the formation of four-stranded DNA structures, and its stabilization by quadruplex-binding agents, in an effort to discover new potent telomerase inhibitors.

Efficient gene transfection by bisguanylated diacetylene lipid formulations.

We have previously shown that cationic cholesterol derivatives bearing guanidinium groups were efficient vectors for gene transfer. To further evaluate the potentiality of this novel class of cationic lipids, we undertook to study the transfection efficiency of guanidinium-based lipids with other hydrophobic moieties. Specifically, we synthesized a reagent where two guanidinium groups are linked to a diacetylene lipid which may provide the lipoplexes with favorable structural features. We report here that the cationic lipid bisguanidinium-diacetylene (BGDA) is highly efficient for in vitro gene transfection when formulated with dioleoylphosphatidyl ethanolamine (DOPE). We also show that liposomes composed of BGDA, DOPE, and a neutral diacetylene colipid, hydroxyethylenediacetylene (HEDA), are efficient for transfection. Thus, diacetylene-based lipids provide a novel scaffold for gene transfection and will be particularly useful for gaining new insights into the structure-activity relationships of the lipid/DNA complexes as they offer a means to study the effects of polymerizable domains.

Interaction of an acridine dimer with DNA quadruplex structures.

The reactivation of telomerase activity in most cancer cells supports the concept that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. The telomeric G-rich single-stranded DNA can adopt an intramolecular G-quadruplex structure in vitro, which has been shown to inhibit telomerase activity. The C-rich sequence can also adopt a quadruplex (intercalated) structure (i-DNA). Two acridine derivatives were shown to increase the melting temperature of the G- quadruplex and the C-quadruplex at 1 microM dye concentration. The increase in Tm value of the G-quadruplex was associated with telomerase inhibition in vitro. The most active compound, "BisA", showed an IC(50) value of 0.75 microM in a standard TRAP assay.

Comparison between experimental and computer simulations of current-voltage (I-V) characteristics of dielectric-coated photon-stimulated field emitters.

For the purpose of simulating photon-stimulated field emission by taking account of three-dimensional aspects, a transfer-matrix formulation of electronic scattering was combined with a Floquet expansion of the wave function for taking account of quanta exchanges between the electrons and the external radiation. With specific techniques to preserve numerical stability, this transfer-matrix formalism is well suited to compute the transmission of the field-emitted/photon-stimulated electrons between two electrodes. This theory is applied to the computation of Fowler-Nordheim curves describing the photon-stimulated field emission of a tungsten plane emitter (described by z< or =0), which supports a nanometric protrusion and a dielectric coating. The extraction bias ranges from 12 to 24V, for an inter-electrode distance of 4nm. The electromagnetic radiation has a wavelength of 0.67 microm and a power flux density ranging from 5.96 x 10(10) to 5.96 x 10(12) W/m2. The effects due to the protrusion and the dielectric coating are studied. These theoretical results are compared with the experimental data.

DNA double helix destabilizing properties of cyclobisintercaland compounds and competition with a single strand binding protein.

The DNA helix destabilizing activity of a series of cyclobisintercaland compounds (CBIs) has been evaluated by measuring their ability to displace a 32P-labelled oligonucleotide primer (17-mer) hybridized to the single stranded DNA of M13. This destabilizing activity appears to be strongly dependent on the cyclic structure (the linear acyclic references are inactive) and the size of the macrocycle; both features being known to determine the preferential binding of the compound to ssDNA. Interestingly, CBIs induced the dissociation of the duplex template in a concentration range (0.5-1 microM) close to that required for the destabilizing activity of single stranded DNA binding proteins (SSBs). Therefore competition experiments between CBIs and an SSB protein (Eco SSB) for binding to a single stranded oligonucleotide target (36-mer) have been performed through gel electrophoresis and nitrocellulose binding assays and strong inhibitory effects on the formation of the SSB:36-mer complex have been observed.

Threading bis-intercalation of a macrocyclic bisacridine at abasic sites in DNA: nuclear magnetic resonance and molecular modeling study.

The macrocyclic bisacridine (CBA) has been reported previously to specifically recognize single-stranded nucleic acid structures, especially DNA hairpins. The binding of the drug with an abasic site-containing oligonucleotide, was investigated by (1)H NMR and molecular modeling. We have used a DNA undecamer, the d(C(1)G(2)C(3)A(4)C(5)X(6)C(7)A(8)C(9)G(10)C(11)) x d(G(12)C(13)G(14)T(15)G(16)T(17)G(18)T(19)G(2)(0)C(21)G(22)) duplex in which the X residue is a stable analogue of the abasic site [3-hydroxy-2-(hydroxymethyl) tetrahydrofuran]. Analysis of the NMR data reveals that the bisacridine molecule forms two different intercalation complexes in a 80/20 (+/- 10) ratio. For the major complex, a molecular modeling study was performed guided by nineteen intermolecular drug-DNA restraints, determined from NOESY spectra. In this model, the ligand interacts in the threading binding mode with an acridine ring intercalated between the C(7)-A(8) and T(15)-G(16) base pairs, while the other acridine ring resides in the abasic pocket. The two linker chains are positioned in the minor and in the major groove, respectively. A comparable study was performed to evaluate the interaction of CBA with the parent unmodified duplex in which X(6) was replaced by an adenine residue. No complex formation was observed when operating in identical conditions. This shows the selective binding of CBA to the abasic site and its potential interest to target the abasic site lesion.

Structural characteristics of supramolecular assemblies formed by guanidinium-cholesterol reagents for gene transfection.

We have recently discovered that cationic cholesterol derivatives characterized by guanidinium polar headgroups are very efficient for gene transfection in vitro and in vivo. In spite of being based on some rationale at the molecular level, the development of these new synthetic vectors was nevertheless empirical. Indeed, the factors and processes underlying cationic lipid-mediated gene transfer are still poorly understood. Thus, to get a better insight into the mechanisms involved, we have examined the supramolecular structure of lipid/DNA aggregates obtained when using reagent bis(guanidinium)-tren-cholesterol (BGTC), either alone or as a liposomal formulation with the neutral phospholipid dioleoyl phosphatidylethanolamine (DOPE). We here report the results of cryotransmission electron microscopy studies and small-angle x-ray scattering experiments, indicating the presence of multilamellar domains with a regular spacing of 70 A and 68 A in BGTC/DOPE-DNA and BGTC-DNA aggregates, respectively. In addition, DNA lipoplexes with similar lamellar patterns were detected inside transfected HeLa cells by conventional transmission electron microscopy. These results suggest that DNA condensation by multivalent guanidinium-cholesterol cationic lipids involves the formation of highly ordered multilamellar domains, the DNA molecules being intercalated between the lipid bilayers. These results also invite further investigation of the intracellular fate of the internalized lipid/DNA structures during their trafficking toward the cell nucleus. The identification of the basic features of active complexes should indeed help in the design of improved guanidinium-based vectors.