Mesoporous self-assembled nanoparticles of biotransesterified cyclodextrins and nonlamellar lipids as carriers of water-insoluble substances.

Soft mesoporous hierarchically structured particles were created by the self-assembly of an amphiphilic deep cavitand cyclodextrin ßCD-nC10 (degree of substitution n = 7.3), with a nanocavity grafted by multiple alkyl (C10) chains on the secondary face of the ßCD macrocycle through enzymatic biotransesterification, and the nonlamellar lipid monoolein (MO). The effect of the non-ionic dispersing agent polysorbate 80 (P80) on the liquid crystalline organization of the nanocarriers and their stability was studied in the context of vesicle-to-cubosome transition. The coexistence of small vesicular and nanosponge membrane objects with bigger nanoparticles with inner multicompartment cubic lattice structures was established as a typical feature of the employed dispersion process. The cryogenic transmission electron microscopy (cryo-TEM) images and small-angle X-ray scattering (SAXS) structural analyses revealed the dependence of the internal organization of the self-assembled nanoparticles on the presence of embedded ßCD-nC10 deep cavitands in the lipid bilayers. The obtained results indicated that the incorporated amphiphilic ßCD-nC10 building blocks stabilize the cubic lattice packing in the lipid membrane particles, which displayed structural features beyond the traditional CD nanosponges. UV-Vis spectroscopy was employed to characterize the nanoencapsulation of a model hydrophobic dimethylphenylazo-naphthol guest compound (Oil red) in the created nanocarriers. In perspective, these dual porosity carriers should be suitable for co-encapsulation and sustained delivery of peptide, protein or siRNA biopharmaceuticals together with small molecular weight drug compounds or imaging agents.

Label-free, optical sensing of the supramolecular assembly into fibrils of a ditryptophan-DNA hybrid.

The grafting of a short nucleic acid strand to ditryptophan dipeptide (WW) results in a peptide-DNA hybrid, which assembles into fibrils under controlled aggregation conditions as evidenced by label free optical sensing owing to the intrinsic fluorescence of the dipeptide.

Self-assembling DNA-peptide hybrids: morphological consequences of oligonucleotide grafting to a pathogenic amyloid fibrils forming dipeptide.

For the very first time, highly efficient synthesis of DNA-peptide hybrids to scaffold self-assembled nanostructures is described. Oligonucleotide conjugation to the diphenylalanine dipeptide triggers a morphological transition from fibrillar to vesicular structures which may potentially be used as delivery vehicles, since they exhibit pH triggered release.

Biological-like vesicular structures self-assembled from DNA-block copolymers.

The polymer modification of short nucleotide sequences has been achieved for future use as self-assembled biologically active structures with sizes in the nanometre range. Co-assembly of the resulting DNA-based amphiphilic block copolymers with native proteins demonstrates the self-assembly of biological-like vesicular structures.

Towards biologically active self-assemblies: model nucleotide chimeras.

With this article, we wish to give an overview of our main research activities assessing the potential of a suitable polymer modification of DNA fragments to self-assemble biologically active nanostructures. Specifically, the grafting of a hydrophobic polymer segment on DNA fragments results in amphiphilic nucleotide-based macromolecules, which, owing to both chemical and physical incompatibility, organize in self-assembled structures either on surfaces or in aqueous solution. Through the combination of the existing know-how in polymer chemistry with modern analytical techniques, we are currently focusing on establishing the mechanism of self-assembly of the polymer-modified nucleotide sequences in solution and on surfaces prior to the assessment of their hybridization capacity once involved in the ensemble. With the evaluation of the potential of the functional nanostructures to undergo biological-like adhesion through hybridization one can eventually foresee that the optimal functionality of these bio-inspired systems could be fine-tuned for biological applications such as drug delivery, gene therapy, tissue engineering and the design of either biomedical devices or biosensors.

Oligonucleotide nanostructured surfaces: effect on Escherichia coli curli expression.

Oligonucleotide model surfaces allowing independent variation of topography and chemical composition were designed to study the adhesion and biofilm growth of E.coli. Surfaces were produced by covalent binding of oligonucleotides and immobilization of nucleotide-based vesicles. Their properties were confirmed through a combination of fluorescence microscopy, XPS, ellipsometry, AFM and wettability studies at each step of the process. These surfaces were then used to study the response of three different strains of E.coli quantified in a static biofilm growth mode. This study led to convincing evidence that oligonucleotide-modified surfaces, independent of the topographical feature used in this study, enhanced curli expression without an increase in the number of adherent bacteria.

Nucleo-copolymers: oligonucleotide-based amphiphilic diblock copolymers.

For the first time, poly(butadiene) has been covalently linked to an oligonucleotide sequence and the resulting nucleo-copolymer exhibits amphiphilic properties in dilute aqueous solution, self-assembling into nanometer-sized vesicular structures.