Vesicle-like Aggregates Research Articles

Interface Adsorption and Aggregation Behavior of Sulfonate-Based Anionic Silicone Surfactants in Aqueous Solution.

A series of sulfonate silicone surfactants possessing different hydrophobic groups were synthesized. Their adsorption and thermodynamic parameters in aqueous solutions were investigated by surface tension measurements, conductivity, transmission electron microscopy and dynamic light scattering. The results suggested that the surface activity and aggregation behavior of these surfactants were clearly influenced by the hydrophobic groups, due to the fact that hydrophobic trimethylsilyl or triethylsilyl groups in these surfactants had good flexibility and high hydrophobicity. This research work will enrich the variety of silicone surfactants and provide theoretical guidance for their potential applications.

Chiral Binaphthalene Building Blocks for Self-Assembled Nanoscale CPL Emitters.

The introduction of biuret hydrogen-bonding sites onto chiral binaphthalene-based chromophores was investigated as a route to sub-micron-sized, vesicle-like aggregates endowed with chiroptical properties. The synthesis was conducted from the corresponding chiral 4,4'-dibromo-1,1'-bis(2-naphthol) via Suzuki-Miyaura coupling to afford luminescent chromophores whose emission spectrum could be tuned from blue to yellow-green through extension of the conjugation. For all compounds, the spontaneous formation of hollow spheres with a diameter of ca. 200-800 nm was evidenced by scanning electron microscopy, along with strong asymmetry in the circularly polarized absorption spectra. For some compounds, the emission also displayed circular polarization with values of glum = ca. 10-3 which could be increased upon aggregation.

Arylazopyrazole as a photo-switch for controllable self-assembly of pillar[6]arene-based supramolecular amphiphiles.

A photo-responsive host-guest molecular recognition between a cationic pillar[6]arene host and an arylazopyrazole derived guest was established. Based on this novel recognition motif, a photo-controllable supra-amphiphile was constructed. The spontaneous aggregation can be reversibly controlled by irradiation with UV (365 nm) and green light (520 nm), leading to a switch between spherical nanoparticles and vesicle-like aggregates.

Cationic Imidazolium Amphiphiles Bearing a Methoxyphenyl Fragment: Synthesis, Self-Assembly Behavior, and Antimicrobial Activity.

Novel cationic amphiphiles of the 3-alkyl-1-(4-methoxyphenyl)-1H-imidazol-3-ium bromide series bearing methoxyphenyl fragments (MPI-n) have been synthesized. Their aggregation properties in aqueous solutions, solubilization capacity, and hemolytic and antimicrobial activities have been investigated by a number of physicochemical methods. Using tensiometry, conductometry, and fluorescence spectroscopy, it was shown that the MPI-n have lower CMCs than their nonfunctionalized counterparts. The unusual alkyl-chain-length-dependent morphology of aggregates is testified for this homological series. Amphiphiles with 12, 14, and 16 alkyl tails are characterized by the formation of micellar aggregates, while a surfactant with a decyl tail is characterized by the formation of larger aggregates with lower surface curvature. The MPI-10 aggregate morphology was rationalized in terms of the packing parameter consideration and was supported by size measurements and the fluorescence probe techniques, which showed that vesicle-like aggregates in close-packing mode probably occur. MPI-n aggregates have exhibited a high solubilization capacity toward hydrophobic azo dye Orange OT. Importantly, amphiphiles studied showed (i) high bacteriostatic activity at the level of ciprofloxacin; (ii) high bactericidal action against all Gram-positive bacteria, including methicillin-resistant strains; (iii) bactericidal properties against Gram-negative bacteria; and (iv) low hemolytic activity.

Interactions between Mutant Bacterial Lipopolysaccharide (LPS-Ra) Surface Layers: Surface Vesicles, Membrane Fusion, and Effect of Ca2+and Temperature.

Lipopolysaccharides (LPS) are a major component of the protective outer membrane of Gram-negative bacteria. Understanding how the solution conditions may affect LPS-containing membranes is important to optimizing the design of antibacterial agents (ABAs) which exploit electrostatic and hydrophobic interactions to disrupt the bacteria membrane. Here, interactions between surface layers of LPS (Ra mutants) in aqueous media have been studied using a surface force apparatus (SFA), exploring the effects of temperature and divalent Ca2+ cations. Complementary dynamic light scattering (DLS) characterization suggests that vesicle-like aggregates of diameter ∼28-80 nm are formed by LPS-Ra in aqueous media. SFA results show that LPS-Ra vesicles adsorb weakly onto mica in pure water at room temperature (RT) and the surface layers are readily squeezed out as the two surfaces approach each other. However, upon addition of calcium (Ca2+) cations at near physiological concentration (2.5 mM) at RT, LPS multilayers or deformed LPS liposomes on mica are observed, presumably due to bridging between LPS phosphate groups and between LPS phosphates and negatively charged mica mediated by Ca2+, with a hard wall repulsion at surface separation D0 ∼ 30-40 nm. At 40 °C, which is above the LPS-Ra β-α acyl chain melting temperature (Tm = 36 °C), fusion events between the surface layers under compression could be observed, evident from δD ∼ 8-10 nm steps in the force-distance profiles attributed to LPS-bilayers being squeezed out due to enhanced fluidity of the LPS acyl-chain, with a final hard wall surface separation D0 ∼ 8-10 nm corresponding to the thickness of a single bilayer confined between the surfaces. These unprecedented SFA results reveal intricate structural responses of LPS surface layers to temperature and Ca2+, with implications to our fundamental understanding of the structures and interactions of bacterial membranes.

Controlling the Miscibility of X-Shaped Bolapolyphiles in Lipid Membranes by Varying the Chemical Structure and Size of the Polyphile Polar Headgroup.

Bolaamphiphiles are well-known naturally occurring structures that can increase the thermal and mechanical stability of the phospholipid membrane by incorporation in a transmembrane manner. Modifications of bolaamphiphiles to introduce particular structural elements such as a conjugated aromatic backbone and lateral side chains in the hydrophobic region lead to bolapolyphiles (BPs). We investigated the ability of BPs to form lyotropic phases in water. The BPs had an identical backbone and side chains, but different headgroup structures, leading to different abilities to act as hydrogen bond donors and acceptors. BPs with hydrophilic headgroups capable of acting as hydrogen bond donors as well as acceptors did not form lyotropic phases and were insoluble in water, independent of whether the polar groups were small or large. The extended lipophilic core structure and the multiple intermolecular hydrogen bonds between the headgroups prevented the formation of well-hydrated lyotropic aggregates. A BP with two large hydrophilic headgroups of several ethylene oxide moieties terminated by methyl groups formed sheet- and vesicle-like aggregates in water. These headgroups act only as hydrogen bond acceptors and cannot form hydrogen bonds in the absence of water. The miscibility of BPs with vesicles of 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) in water and the resulting aggregate structures were also investigated. For BPs with headgroups acting as donors and acceptors of hydrogen bonds, macroscopic phase separation occurred in the mixed membranes, and two different membrane domains, a DPPC-rich one containing only little polyphile and a BP-rich one containing varying amounts of lipid, were formed. For headgroups without the ability to act as hydrogen bond donors, small BP aggregates were formed that were homogeneously distributed over the membrane. The lateral organization of BPs in lipid membranes can thus be controlled by the nature of the BP headgroup.

Cationic amphiphilic bolaamphiphile-based delivery of antisense oligonucleotides provides a potentially microbiome sparing treatment for C. difficile.

Conventional antibiotics for C. difficile infection (CDI) have mechanisms of action without organismal specificity, potentially perpetuating the dysbiosis contributing to CDI, making antisense approaches an attractive alternative. Here, three (APDE-8, CODE-9, CYDE-21) novel cationic amphiphilic bolaamphiphiles (CABs) were synthesized and tested for their ability to form nano-sized vesicles or vesicle-like aggregates (CABVs) which were characterized based on their physiochemical properties, their antibacterial activities, and their toxicity toward colonocyte (Caco-2) cell cultures. The antibacterial activity of empty CABVs were tested against cultures of E. coli, B. fragilis and E. faecalis, and against C. difficile by “loading” CABVs with 25-mer antisense oligonucleotides (ASO) targeting dnaE. Our results demonstrate that empty CABVs have minimal colonocyte toxicity until concentrations of 71 μM, with CODE-9 demonstrating the least toxicity. Empty CABVs had little effect on C. difficile growth in culture (MIC90 ≥160 μM). While APDE-8 and CODE-9 nanocomplexes demonstrated high MIC90 against C. difficile cultures (>300 μM), CYDE-21 nanocomplexes demonstrated MIC90 at CABV concentrations of 19 μM. Empty CABVs formed from APDE-8 and CODE-9 had virtually no effect on E. coli, B. fragilis and E. faecalis across all tested concentrations, while empty CYDE-21 demonstrated MIC90 of >160 μM against E. coli and >40μM against B. fragilis and E. faecalis.Empty CABVs have limited antibacterial activity and they can deliver an amount of ASO effective against C. difficile at CABV concentrations associated with limited colonocyte toxicity, while sparing other bacteria. With further refinement, antisense therapies for CDI may become a viable alternative to conventional antibiotic treatment.

Hydrophilicity and flexibility of the spacer as critical parameters on the aggregation behavior of long alkyl chain cationic gemini surfactants in aqueous solution

Abstract Series of quaternary ammonium-based gemini surfactants with long alkyl chains (C12 and C18) containing different spacers and substituents attached to the polar head group have been synthesized and their aggregation properties in aqueous solution examined. The effect of the hydrophobic chain, the nature and structure of the spacer group and the polarity of the head group on the aggregation behavior of such dimeric surfactants has been investigated. The critical micelle concentration (cmc) values of gemini surfactants in aqueous solution were determined by conductivity, steady state fluorescence and potentiometric measurements. The size of aggregates formed by investigated amphiphiles above the cmc in aqueous solution was examined by dynamic light scattering. Gemini surfactants show cmc values significantly lower than those of comparable single chain surfactants. The tendency of trimeric surfactants with a rigid spacer to form aggregates is higher than that of the corresponding dimeric surfactants. As occurs for monomeric ionic surfactants, the cmc of gemini surfactants decreases with the elongation of the hydrophobic chain. However, the effect of lengthening the alkyl chain on the cmc depends on the structure of the spacer. C12 gemini surfactants with a rigid hydrophobic spacer exhibit cmc higher than those containing a flexible hydrophobic spacer. For gemini surfactants with C18 alkyl chains this effect is even more pronounced and leads to differences in cmc values greater than one order of magnitude. The structure of the spacer, flexible or rigid chain, has been found to be a critical parameter on the self-assembly of long chain gemini surfactants. Spherical micelles are spontaneously formed above the cmc for C12 gemini surfactants, whereas trimeric and C18 gemini surfactants seems to form vesicle-like aggregates when self-aggregation occurs.

Out of Equilibrium Self-Assembly of Janus Nanoparticles: Steering It from Disordered Amorphous to 2D Patterned Aggregates

Solvent evaporation driven self-assembly of Janus nanoparticles (J-NPs) has been simulated employing lattice-gas models to investigate the possible emergence of new superlattices. Depending on the chemical nature of NP faces (hence solvophilicity and relative interaction strength), zebra-like or check-like patterns and micellar agglomerates can be obtained. Vesicle-like aggregates can be produced by micelle-based corrals during heterogeneous evaporation. Patterns formed during aggregation appear to be robust against changes in evaporation modality (i.e., spinodal or heterogeneous) or interaction strengths, and they are due to a strictly nanoscopic orientation of single J-NPs in all cases. Due to the latter feature, the aggregate size growth law N(t) ∝ ta has its exponent a markedly depending on the chemical nature of the J-NPs involved in spite of the unvaried growth mechanism. We interpret such a finding as connected to the increasingly stricter orientation pre-requirements for successful (binding) NP landing upon going from isotropic (a ≃ 0.50), to "zebra" (a ≃ 0.38), to "check" (a ≃ 0.23), and finally to "micelle" (a = 0.15-0.17) pattern forming NPs.

Construction of a Soluble Supramolecular Glutathione Peroxidase Mimic based on Host-Guest Interaction

A soluble glutathione peroxidase mimic with the optimum structure (NCD-Te-NCD2.2) was constructed based on the supramolecular host-guest interaction. The self-assembled structure and catalytic mechanism of NCD-Te-NCD2.2 were detailed investigation. It was proved that NCD-Te-NCD2.2 could form the hollow vesicle-like aggregates in water. And saturation kinetics measurement indicated that NCD-Te- NCD2.2 exhibited the typical enzyme catalytic behavior. Furthermore, benefited from the hydrophobic microenvironment in vesicle-like aggregates, NCD-Te-NCD2.2 exhibited the specific recognition ability for hydrophobic substrates, which was one of the important characteristics of native glutathione peroxidase. The successful construction of NCD-Te-NCD2.2 not only provides an efficient preparation method for soluble GPx mimic but also highlights for construction of other giant supramolecular biomimetic enzymes. Keywords: Biomimetics, enzyme activity, glutathione peroxidase, supramolecular, host-guest interaction.

Aqueous dispersion of metal oxide nanoparticles, using siloxane surfactants

Siloxane surfactants containing tromethamol or carboxylate groups, with very good surface properties, are tested for the first time for biocompatibility using MTT cytotoxicity test. They are used for encapsulation of superparamagnetic iron oxide nanoparticles (SPION), and of a combination of these with nystatin as model un-soluble drug, in order to obtain stable aqueous dispersions. The initial magnetite and chromite nanoparticles have been synthesized previously by thermal decomposition thus being covered by dodecylamine and oleic acid. Their aqueous dispersions were obtained by physical methods using very low concentrations of siloxane surfactants, and were investigated by DLS, TEM, cryo-TEM and EDX. One such formulation was tested by MTT method and the results showed high cell viability. The nanoparticles covered with siloxane surfactants exhibited various types of morphology: individual particles, vesicle-like aggregates or composite particles, all having diameters roughly between 20 and 200nm. The encapsulation of both SPION and nystatin confirmed our previous results on nystatin solubilization by encapsulation within the hydrophobic wall of surfactant vesicles.

Self-Assembly of Janus Ellipsoids II: Janus Prolate Spheroids

In self-assembly, the anisotropy of the building blocks and their formation of complex structures have been the subject of considerable recent research. Extending recent research on Janus particles and completing the study of Janus spheroids, we conduct a systematic investigation on the self-assembly of Janus prolate spheroids based on a primitive model that we proposed. Janus prolate spheroids are particles that have a prolate spheroidal body and two hemi-surfaces along the major axis coded with different chemical properties. Using Monte Carlo simulations, we investigate the effects of the aspect ratio on the self-assembly process. In contrast to the vesicle-like aggregates for Janus oblate spheroids, we obtain various ordered cluster structures for Janus prolate spheroids through self-assembly. With an increasing aspect ratio, we find a transition of cluster morphology, from vesicles to tubular micelles and micelles. In particular, a relatively small change in the aspect ratio leads to a rather significant change in morphology. We apply a cluster analysis to understand the mechanism associated with such a transition.

Spontaneous Formation of Artificial Vesicles in Organic Media through Hydrogen-Bonding Interactions

The unusual spontaneous formation of submicrometer-sized vesicles from a small, nonamphiphilic bis-biuret difluorene derivative upon dissolution of the solid in an anhydrous organic solvent was investigated using multiple scattering techniques. Time-resolved light scattering (TLS) measurements confirm that the self-assembly process is driven by hydrogen-bonding interactions, leading to the formation of vesicles at a critical concentration ∼1 × 10–4 M in tetrahydrofuran as determined by absorbance and surface tension measurements. Results from cryogenic-scanning electron microscopy (cryo-SEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS) experiments are consistent with the existence of vesicle-like aggregates in solution. DLS studies indicate a broad distribution of aggregates with a mean hydrodynamic radius ⟨RH⟩ = 303 nm (polydispersity =0.49). SAXS profiles show two decay regimes (low-Q decay, very large aggregates; large-Q decay, smaller species). The analysis models the large aggregates as vesicles (hollow spheres) with a mean external radius Ro = 750 nm and an internal radius Ri = 720 nm while the smaller aggregates have a mean radius R = 2.2 nm. The results obtained by cryo-SEM show spherical aggregates of vesicles size in the range ca. 100 nm to 1 μm. Transmission electron microscopy (TEM) micrographs evidence the presence of aggregates whose morphology is compatible with budding and pearling processes as possible mechanisms for the formation of vesicles.

Lipid layer engineering of poly(lactide-co-glycolide) nanoparticles to control their uptake and intracellular co-localisation.

Poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were prepared by an O/W emulsion-solvent evaporation method with polyethyleneimine (PEI) in the water phase as a stabiliser. Layer-by-Layer (LbL) assembly was used to engineer the surface of the NPs. Then, the multilayer coated PLGA NPs were further modified via self-assembly with lipid vesicles composed of 1,2-dioleoyl-sn-glycero-3-choline (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS) at different molar ratios: 65 : 35, 75 : 25, 85 : 15 and 95 : 5. The influence of the lipid composition of the NPs on cellular uptake and uptake pathways for the HepG2 cell line was studied by means of flow cytometry and confocal laser scanning microscopy (CLSM). Macropinocytosis, clathrin-mediated and caveolae-mediated endocytosis are the main internalisation pathways of the lipid coated PLGA NPs. Lipid coated PLGA NPs tend to form vesicle-like aggregates in close proximity to the nucleus. Co-localisation studies indicate that lipid coated NPs could be associated with the endoplasmic reticulum (ER). Decreasing the proportion of negatively charged DOPS in the lipid coating results in a decrease in NP uptake and an increase in the presence of vesicle-like aggregates with an apparently higher association with the ER.

Pillar[6]arene-Based Photoresponsive Host–Guest Complexation

The trans form of an azobenzene-containing guest can complex with a pillar[6]arene, while it cannot complex with pillar[5]arenes due to the different cavity sizes of the pillar[6]arene and the pillar[5]arenes. The spontaneous aggregation of its host-guest complex with the pillar[6]arene can be reversibly photocontrolled by irradiation with UV and visible light, leading to a switch between irregular aggregates and vesicle-like aggregates. This new pillar[6]arene-based photoresponsive host-guest recognition motif can work in organic solvents and is a good supplement to the existing widely used cyclodextrin/azobenzene recognition motif.

Photocontrolled Self-Assembly and Disassembly of Block Ionomer Complex Vesicles: A Facile Approach toward Supramolecular Polymer Nanocontainers

A new concept of designing a photocontrollable supramolecular polymer nanocontainer through the electrostatic association between an azobenzene-containing surfactant (AzoC10) and a double-hydrophilic block ionomer, poly(ethylene glycol)-b-poly(acrylic acid) (PEG(43)-PAA(153)), is described. Such a block ionomer complex can self-assemble in aqueous solution and form vesicle-like aggregates, which are composed of a poly(ethylene glycol) corona and a poly(acrylic acid) shell associated with azobenzene-containing surfactant. The photoisomerization of azobenzene moieties in the block ionomer complex can reversibly tune the amphiphilicity of the surfactants, inducing the disassembly of the vesicles. Such block ionomer complex vesicles are further evaluated as nanocontainers capable to encapsulate and release guest solutes on demand controlled by light irradiation. For example, the vesicles encapsulating the fluorescein sodium display clear spherical images observed by fluorescence microscopy. However, such fluorescence-marked images disappear after releasing the solute from the vesicles triggered by the UV light. Such novel materials are of both basic and practical significance, especially as prospective nanocontainers for cargo delivery.

Synthesis and Characterization of a New Gemini Surfactant Derived from 3α,12α-Dihydroxy-5β-cholan-24-amine (Steroid Residue) and Ethylenediamintetraacetic Acid (Spacer)

A new gemini steroid surfactant derived from 3alpha,12alpha-dihydroxy-5beta-cholan-24-amine (steroid residue) and ethylenediamintetraacetic acid (spacer) was synthesized and characterized in aqueous solution by surface tension, fluorescence intensity of pyrene, and light scattering (static and dynamic) measurements. These techniques evidence the existence of a threshold concentration (cac), below which a three layers film is formed at the air-water interface. Above the cac, two types of aggregates--micelles and vesicle-like aggregates--coexist in a metastable state. Filtration of a solution with a starting concentration of 2.6 mM (buffer 150 mM, pH 10) allows isolation of the micelles, which have an average aggregation number of 12, their density being 0.28 g cm(-3). Under conditions where only the vesicle-like aggregates are detected by dynamic light scattering, a value of 5.5 x 10(4) was obtained for their aggregation number at 30 microM, their density being 6.8 x 10(-4) g cm(-3). At high concentrations, the intensity ratio of the vibronic peaks of pyrene, I1/I3, (=0.68) is very close to published values for deoxycholate micelles, indicating that the probe is located in a region with a very low polarity and far from water. A hypothesis to explain the observed aggregation behavior (small aggregates are favored with increasing gemini concentration) is outlined.

Self-dissociation of water-soluble PANa/ETC nano-aggregates

Complexation between poly(sodium acrylate) (PANa) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (ETC) in water, which leads to the formation of vesicle-like aggregates, was studied. Different from reported nano-aggregates of polymer complexes that may dissociate when being stimulated, the nano-aggregates of PANa/ETC complexes dissociate automatically in the aqueous solution at ambient environment, exhibiting a behavior similar to that of the nano-aggregates composed of degradable polymers. In the newly formed nano-aggregates, there are hydrophobic domains with a hydrophobicity close to that of hexane. Along with the dissociation, the hydrophobic domains vanish gradually.

Photocontrolled Reversible Supramolecular Assemblies of an Azobenzene‐Containing Surfactant with α‐Cyclodextrin

Inclusion and exclusion of an azobenzene-containing surfactant with α-cyclodextrin (α-CD) can be used to fabricate photostimulus-responsive vesicle-like aggregates that can undergo assembly and disassembly reversibly (see picture). The movement of α-CD is like that of a molecular shuttle.

Core−Shell Reversion of Hybrid Polymeric Micelles Containing Gold Nanoparticles in the Core

The micellization of polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) in chloroform can be induced by the interaction between P4VP blocks and HAuCl4, forming micelles with PS as the shell and the P4VP/HAuCl4 complex as the core. Subsequent reduction of HAuCl4 leads to hybrid polymeric micelles (HPMs) containing gold nanoparticles (GNs) in the core. In this case, protonation of P4VP block by hydrochloride acid is necessary for the stabilization of HPMs. Further study demonstrates that switching the solvent gradually and continuously from chloroform to a methanol/chloroform (9/1, v/v) mixture, where protonated P4VP is soluble whereas PS is insoluble, leads to a core−shell reversion of the HPMs, forming vesicle-like aggregates with PS as the wall and protonated P4VP/GNs as the shell. The interaction between GNs and protonated pyridine repeating units is a necessary driving force for stable attachment of GNs to shell. When the P4VP block is deprotonated, the GNs will be released from the shell to form precipitates, whereas the vesicles are still stable in the solution. It is also found that during the core−shell reversion the aggregation of PS chains occurs at first among the shell of the HPMs, and then the dissociation of the core happens due to the continuous addition of methanol into the solution, leading to the core−shell reversion. This indicates that there is no intermediate state of the molecularly dispersed block copolymer existing between the HPMs and the RHPMs.