New hybrid magnetic nanoparticles based on chitosan-maltose derivative for antitumor drug delivery.

The aim of the present study is to obtain, for the first time, polymer magnetic nanoparticles based on the chitosan-maltose derivative and magnetite. By chemically modifying the chitosan, its solubility in aqueous media was improved, which in turn facilitates the nanoparticles' preparation. Resulting polymers exhibit enhanced hydrophilia, which is an important factor in increasing the retention time of nanoparticles in the blood flow. The preparation of nanoparticles relied on the double crosslinking technique (ionic and covalent) in reverse emulsion which ensures the mechanical stability of the polymer carrier. The characterization of both the chitosan derivative and nanoparticles was accomplished by Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance Spectroscopy, Scanning Electron Microscopy, Transmission Electron Microscopy, Atomic Force Microscopy, Vibrating Sample Magnetometry, and Thermogravimetric Analysis. The evaluation of morphological, dimensional, structural, and magnetical properties, as well as thermal stability and swelling behavior of nanoparticles was made from the point of view of the polymer/magnetite ratio. The study of 5-Fluorouracil loading and release kinetics as well as evaluating the cytotoxicity and hemocompatibility of nanoparticles justify their adequate behavior in their potential use as devices for targeted transport of antitumor drugs.

Self-assembly of proteins into a three-dimensional multilayer system: investigation of the surface of the human fungal pathogen Aspergillus fumigatus.

Hydrophobins are small surface active proteins that fulfil a wide spectrum of functions in fungal growth and development. The human fungal pathogen Aspergillus fumigatus expresses RodA hydrophobins that self-assemble on the outer conidial surface into tightly organized nanorods known as rodlets. AFM investigation of the conidial surface allows us to evidence that RodA hydrophobins self-assemble into rodlets through bilayers. Within bilayers, hydrophilic domains of hydrophobins point inward, thus making a hydrophilic core, while hydrophobic domains point outward. AFM measurements reveal that several rodlet bilayers are present on the conidial surface thus showing that proteins self-assemble into a complex three-dimensional multilayer system. The self-assembly of RodA hydrophobins into rodlets results from attractive interactions between stacked ß-sheets, which conduct to a final linear cross-ß spine structure. A Monte Carlo simulation shows that anisotropic interactions are the main driving forces leading the hydrophobins to self-assemble into parallel rodlets, which are further structured in nanodomains. Taken together, these findings allow us to propose a mechanism, which conducts RodA hydrophobins to a highly ordered rodlet structure. The mechanism of hydrophobin assembly into rodlets offers new prospects for the development of more efficient strategies leading to disruption of rodlet formation allowing a rapid detection of the fungus by the immune system.

Control of swelling of responsive nanogels by nanoconfinement.

The volume phase transition (VPT) behavior and the swelling properties of individual thermoresponsive poly(N-isopropylacrylamide) (PNIPAM)-based nanogels are investigated by in situ atomic force microscopy (AFM). Using a template-based synthesis method, cylindrical nanogels are synthesized for different polymerization times within nanopores (80 nm) of poly(ethylene terephthalate) (PET) track-etched membranes. The confinement conditions, characterized by the ratio Φ between the average chain length and the pore diameter, are varied between 0.35 and 0.8. After dissolving the membranes, the volume of individual nanogels composed of PNIPAM-g-PET diblock copolymers is numerically extracted from AFM images while varying the water temperature from 28 to 44 °C. From the measured volumes, the swelling of nanogels is investigated as a function of both the water temperature and the confinement conditions imposed during the synthesis. Contrary to the VPT, the maximum swelling of the nanogels is strongly affected by these confinement conditions. The volume of nanogels in the swollen state can reach 1.1 to 2.1 times their volume in the collapsed state for a ratio Φ of 0.8 and 0.5, respectively. These results open a new way to tune the swelling of nanogels, simply by adjusting the degree of confinement imposed during their synthesis within nanopores, which is particularly interesting for biomedical applications requiring a high degree of control over swelling properties, such as drug-delivery nanotools.

Variation of elastic properties of responsive polymer nanotubes.

The mechanical properties of thermo-responsive nanoribbons made of poly(N-isopropylacrylamide)-block-poly(ethylene terephthalate) (PNIPAM-b-PET) have been investigated. The nanoribbons are produced by grafting PNIPAM chains from the walls of nanopores of PET track-etched membranes, by dissolving the membranes. The swelling ratio and elastic modulus of the nanoribbons are evaluated as a function of polymer chain length and temperature, from atomic force microscopy (AFM) images and using the thermodynamic theory of swelling. Whereas the elastic properties of nanoribbons are similar to those of PNIPAM gels and brushes when the PNIPAM chain length is low, they increase by 2 orders of magnitude when the chain length becomes similar to the diameter of the nanopores used to synthesize them. This indicates that PNIPAM brushes synthesized in severe conditions of confinement are strongly cross-linked, either due to irreversible trapping of entanglements, or chemical cross-linking occurring in the dense reaction medium. This provides a way to modulate mechanical properties of soft nanostructures, by playing with the degree of confinement of the chains during synthesis.