Targeting protein-loaded CB[8]-mediated supramolecular nanocarriers to cells

Supramolecular amphiphiles, consisting of ternary complexes of cucurbit[8]uril (CB[8]), an alkylated paraquat derivative and a tetraethylene glycol-functionalized azobenzene, self-assemble into vesicles of about 200 nm in diameter. The outer surface of the vesicles was functionalized with cell-targeting ligands. These vesicles were employed for loading and delivery of proteins into cells. Supramolecular amphiphile-derived vesicles show great promise as nanocarriers of functional molecules to be transferred into cells

Programmed disassembly of supramolecular nanoparticles stabilized by heteroternary CB[8] host-guest interactions

Controlled release is an important determinant of the in-vivo performance of drug delivering nanoparticles (NPs). Therefore the control over and understanding of the release mechanism, e.g. by disassembly or degradation of the carrier, is essential for the optimization of NP formulations. This paper presents a supramolecular toolbox approach for the formation and UV-induced disassembly of supramolecular nanoparticles (SNPs) which are either exclusively stabilized by cucurbit[8]uril (CB[8])/methyl viologen (MV)/azobenzene (Azo) interactions or CB[8]/MV/naphthol (Np) interactions, or by a combination of both. Photoisomerization of the Azo units enables UV-triggered disassembly of the CB[8]/MV/Azo host-guest complex. Depending on the valency of the electron-rich guest moieties (Np or Azo), either SNPs with a UV-responsive shell or a UV-responsive core were formed by assembling SNPs using a mixture of Azo and Np bearing guest molecules. In contrast, non-responsive SNPs or SNPs which disintegrate at both the core and the shell were formed by using exclusively CB[8]/MV/Np or CB[8]/MV/Azo interactions, respectively

Dual stimuli-responsive self-assembled supramolecular nanoparticles

Supramolecular nanoparticles (SNPs) encompass multiple copies of different building blocks brought together by specific noncovalent interactions. The inherently multivalent nature of these systems allows control of their size as well as their assembly and disassembly, thus promising potential as biomedical delivery vehicles. Here, dual responsive SNPs have been based on the ternary host–guest complexation between cucurbit[8]uril (CB[8]), a methyl viologen (MV) polymer, and mono- and multivalent azobenzene (Azo) functionalized molecules. UV switching of the Azo groups led to fast disruption of the ternary complexes, but to a relatively slow disintegration of the SNPs. Alternating UV and Vis photoisomerization of the Azo groups led to fully reversible SNP disassembly and reassembly. SNPs were only formed with the Azo moieties in the trans and the MV units in the oxidized states, respectively, thus constituting a supramolecular AND logic gate

Multivalent interaction of cyclodextrin vesicles, carbohydrate guests, and lectins: A kinetic investigation

An artificial glycocalix self-assembles when unilamellar bilayer vesicles of amphiphilic β-cyclodextrins are decorated with maltose-and lactose-adamantane conjugates by host-guest interactions. The maltose-decorated vesicles aggregate in the presence of lectin concanavalin A whereas the lactose-decorated vesicles aggregate in the presence of lectin peanut agglutinin. The kinetics of the orthogonal multivalent interfacial interactions present in this ternary system of vesicles, carbohydrates, and lectins were studied by time-dependent measurements of the optical density at 400 nm. The average vesicle and vesicle aggregate sizes were monitored by dynamic light scattering. The aggregation process was evaluated as a function of lectin concentration, vesicle concentration, and surface coverage of the vesicles by the carbohydrate-adamantane conjugates. The initial rate of vesicle aggregation scales linearly with the lectin as well as the cyclodextrin vesicle concentration. Furthermore, each lectin requires a characteristic critical density of carbohydrates at the vesicle surface. These observations allow a prediction of the response of the ternary supramolecular system at different concentrations of its components. Also, the effective binding site separation in a multivalent receptor such as a multiple binding site protein can be accurately determined. This methodology can be extended to multivalent noncovalent interactions in other ligand-receptor systems at interfaces. © 2010 American Chemical Society.Fil: Vico, Raquel Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Voskuhl, Jens. Westfalische Wilhelms Universitat; AlemaniaFil: Ravoo, Bart Jan. Westfalische Wilhelms Universitat; Alemani

Sugar-Decorated Sugar Vesicles: Lectin-Carbohydrate Recognition at the Surface of Cyclodextrin Vesicles

An artificial glycocalix self-assembles when unilamellar bilayer vesicles of amphiphilic beta-cyclodextrins are decorated with maltose and lactose by host-guest interactions. To this end, maltose and lactose were conjugated with adamantane through a tetra(ethyleneglycol) spacer. Both carbohydrate-adamantane conjugates strongly bind to beta-cyclodextrin (K(a) approximate to 4 x 10(4) M(-1)). The maltose-decorated vesicles readily agglutinate (aggregate) in the presence of the lectin concanavalin A, whereas the lactose-decorated vesicles agglutinate in the presence of peanut agglutinin. The orthogonal multivalent interaction in the ternary system of host vesicles, guest carbohydrates, and lectins was investigated by using isothermal titration calorimetry, dynamic light scattering, UV/Vis spectroscopy, and cryogenic transmission electron microscopy. It was shown that agglutination is reversible, and the noncovalent interaction can be suppressed and eliminated by the addition of competitive inhibitors, such as D-glucose or beta-cyclodextrin. Also, it was shown that agglutination depends on the surface coverage of carbohydrates on the vesicles

Agglutination of bacteria using poyvalent nanoparticles of aggregation-induced emissive thiophthalonitrile dyes

A novel class of aggregation-induced emissive bis(phenylthio)phthalonitrile dyes were synthesized. These dyes assembled into nanoparticles that were equipped with mannose units. The nanoparticles underwent selective interactions with lectins and bacteria. The bright fluorescent aggregates aid in the visualization of the agglutination of bacteria

Covalent Attachment of Aggregation-Induced Emission Molecules to the Surface of Ultrasmall Gold Nanoparticles to Enhance Cell Penetration

Three different alkyne-terminated aggregation-induced emission molecules based on a para-substituted di-thioether were attached to the surface of ultrasmall gold nanoparticles (2 nm) by copper-catalyzed azide–alkyne cycloaddition (click chemistry). They showed a strong fluorescence and were well water-dispersible, in contrast to the dissolved AIE molecules. The AIE-loaded nanoparticles were not cytotoxic and easily penetrated the membrane of HeLa cells, paving the way for an intracellular application of AIE molecules, e.g., for imaging

Probing the self-assembly and stability of oligohistidine based rod-like micelles by aggregation induced luminescence

The synthesis and self-assembly of a new C2-symmetric oligohistidine amphiphile equipped with an aggregation induced emission luminophore is reported. We observe the formation of highly stable and ordered rod-like micelles in phosphate buffered saline, with a critical aggregation concentration below 200 nM. Aggregation induced emission of the luminophore confirms the high stability of the anisotropic assemblies in serum.</p