Solid Lipid Nanoparticles for Image-Guided Therapy of Atherosclerosis.

Although the application of nanotechnologies to atherosclerosis remains a young field, novel strategies are needed to address this public health issue. In this context, the magnetic resonance imaging (MRI) approach has been gradually investigated in order to enable image-guided treatments. In this contribution, we report a new approach based on nucleoside-lipids allowing the synthesis of solid lipid nanoparticles (SLN) loaded with iron oxide particles and therapeutic agents. The insertion of nucleoside-lipids allows the formation of stable SLNs loaded with prostacycline (PGI2) able to inhibit platelet aggregation. The new SLNs feature better relaxivity properties in comparison to the clinically used contrast agent Feridex, indicating that SLNs are suitable for image-guided therapy.

Epoxy-terminated self-assembled monolayers containing internal urea or amide groups.

We report the synthesis of new coupling agents with internal amide or urea groups possessing an epoxy-terminal group and trimethoxysilyl-anchoring group. The structural characterizations of the corresponding self-assembled monolayers (SAMs) were performed by polarization modulation infrared reflection adsorption spectroscopy (PM-IRRAS). The molecular assembly is mainly based on the intermolecular hydrogen-bonding between adjacent amide or urea groups in the monolayers. Because of the steric hindrance of amide or urea groups, the distance between the alkyl chains is too large to establish van der Waals interactions, inducing their disorder. The reactivity of the epoxy-terminal groups was successfully investigated through reaction with a fluorescent probe. We show that SAMs containing internal urea or amide groups exhibited a higher density of accessible epoxide groups than the corresponding long-chain (C22) glycidyl-terminated SAM.

Control of stem-cell behavior by fine tuning the supramolecular assemblies of low-molecular-weight gelators.

Controlling the behavior of stem cells through the supramolecular architecture of the extracellular matrix remains an important challenge in the culture of stem cells. Herein, we report on a new generation of low-molecular-weight gelators (LMWG) for the culture of isolated stem cells. The bola-amphiphile structures derived from nucleolipids feature unique rheological and biological properties suitable for tissue engineering applications. The bola-amphiphile-based hydrogel scaffold exhibits the following essential properties: it is nontoxic, easy to handle, injectable, and features a biocompatible rheology. The reported glycosyl-nucleoside bola-amphiphiles (GNBA) are the first examples of LMWG that allow the culture of isolated stem cells in a gel matrix. The results (TEM observations and rheology) suggest that the supramolecular organizations of the matrix play a role in the behavior of stem cells in 3D environments.

Functionalized hydrogen-bonding self-assembled monolayers grafted onto SiO2 substrates.

A novel urea coupling agent possessing a vinyl-terminal group and trimethoxysilyl anchoring group was synthesized and grafted onto SiO(2)/Au substrates. This ureido coupling agent exhibits a good capacity to directly yield homogeneous SAMs with a surface smoothing. Polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) was used to monitor these SAMs. Indeed, the different functional groups (alkyl chain, urea, and vinyl) of this coupling agent were clearly observed in the PM-IRRAS spectra. Chemical modifications of the terminal function for the covalent immobilization of biomolecules were monitored by PM-IRRAS for the first time. We have demonstrated the successful reactions of the conversion of the vinyl-terminated SAMs successively into SAM-COOH and SAM-NHS without any degradation of the monolayer. The reactivity of activated esters was successfully investigated in order to immobilize the protein A.

PM-IRRAS investigation of self-assembled monolayers grafted onto SiO2/Au substrates.

Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) was used to characterize self-assembled monolayers (SAMs). Novel ester-terminated organosilicon coupling agents possessing a trialkoxysilyl headgroup and a urea group in the linear alkyl chains (4) were synthesized and grafted onto SiO(2)/Au substrates (SiO(2) film of 200 Å thickness deposited on gold mirror). This composite substrate allowed the anchoring of SAMs and preserved the high reflectivity for infrared radiation. PM-IRRAS spectra with very high signal-to-noise ratios have been obtained in the mid-infrared spectral range allowing monitoring of the grafted SAMs. Quantitative analysis of the measured signal is described to compare PM-IRRAS and conventional IRRAS spectra. This quantitative analysis has been validated since the band intensities in the corrected PM-IRRAS and conventional IRRAS spectra are identical. Orientation information on the different functional groups has been obtained comparing the corrected PM-IRRAS spectrum with the one calculated using isotropic optical constants of ester-terminated organosilicon coupling agents 4. The carbonyls of the urea groups are preferentially parallel to the substrate surface favoring intermolecular hydrogen bonding and consequently a close packing of the molecules attached to the surface. By contrast, the alkyl chains present gauche defects and are poorly oriented.

Low molecular weight hydrogels derived from urea based-bolaamphiphiles as new injectable biomaterials.

There is a critical need for soft materials in the field of regenerative medicine and tissue engineering. However, designing injectable hydrogel scaffolds encompassing both adequate mechanical and biological properties remains a key challenge for in vivo applications. Here we use a bottom-up approach for synthesizing supramolecular gels to generate novel biomaterial candidates. We evaluated the low molecular weight gels candidates in vivo and identified one urea-containing molecule, compound 16, that avoid foreign body reactions in mice. The self-assembly of bolaamphiphiles creates a unique hydrogel supramolecular structures featuring fast gelation kinetics, high elastic moduli, thixotropic, and thermal reversibility properties. This soft material, which inhibits recognition by macrophages and fibrous deposition, exhibits long-term stability after in vivo injection.

Cation Tuning of Supramolecular Gel Properties: A New Paradigm for Sustained Drug Delivery.

Hydrogels formed by the self-assembly of low-molecular-weight gelators (LMWGs) are promising scaffolds for drug-delivery applications. A new biocompatible hydrogel, resulting from the self-assembly of nucleotide-lipid salts can be safely injected in vivo. The resulting hydrogel provides sustained-release of protein for more than a week.

Carbamate-Based Bolaamphiphile as Low-Molecular-Weight Hydrogelators.

A new bolaamphiphile analog featuring carbamate moieties was synthesized in six steps starting from thymidine. The amphiphile structure exhibits nucleoside-sugar polar heads attached to a hydrophobic spacer via carbamate (urethane) functions. This molecular structure, which possesses additional H-bonding capabilities, induces the stabilization of low-molecular-weight gels (LMWGs) in water. The rheological studies revealed that the new bolaamphiphile 7 stabilizes thixotropic hydrogels with a high elastic modulus (G' > 50 kPa).