Measuring the bending rigidity of microbial glucolipid (biosurfactant) bioamphiphile self-assembled structures by neutron spin-echo (NSE): interdigitated vesicles, lamellae and fibers

Bending rigidity, k, is classically measured for lipid membranes to characterize their nanoscale mechanical properties as a function of composition. Widely employed as a comparative tool, it helps understanding the relationship between the lipid's molecular structure and the elastic properties of its corresponding bilayer. Widely measured for phospholipid membranes in the shape of giant unilamellar vesicles (GUVs), bending rigidity is determined here for three self-assembled structures formed by a new biobased glucolipid bioamphiphile, rather associated to the family of glycolipid biosurfactants than phospholipids. In its oleyl form, glucolipid G-C18:1 can assemble into vesicles or crystalline fibers, while in its stearyl form, glucolipid G-C18:0 can assemble into lamellar gels. Neutron spin-echo (NSE) is employed in the q-range between 0.3 nm-1 (21 nm) and 1.5 nm-1 (4.1 nm) with a spin-echo time in the range of up to 500 ns to characterize the bending rigidity of three different structures (Vesicle suspension, Lamellar gel, Fiber gel) solely composed of a single glucolipid. The low (k= 0.30 $\pm$ 0.04 kbT) values found for the Vesicle suspension and high values found for the Lamellar (k= 130 $\pm$ 40 kbT) and Fiber gels (k= 900 $\pm$ 500 kbT) are unusual when compared to most phospholipid membranes. By attempting to quantify for the first time the bending rigidity of self-assembled bioamphiphiles, this work not only contributes to the fundamental understanding of these new molecular systems, but it also opens new perspectives in their integration in the field of soft materials

Myelin figures from microbial glycolipid biosurfactant amphiphiles

Myelin figures (MFs) -- cylindrical lyotropic liquid crystalline structures consisting of concentric arrays of bilayers and aqueous media -- arise from the hydration of the bulk lamellar phase of many common amphiphiles. Prior efforts have concentrated on the formation, structure, and dynamics of myelin produced by phosphatidylcholine (PC)-based amphiphiles. Here, we study the myelinization of glycolipid microbial amphiphiles, commonly addressed as biosurfactants, produced through the process of fermentation. The hydration characteristics (and phase diagrams) of these biological amphiphiles are atypical (and thus their capacity to form myelin) because unlike typical amphiphiles, their molecular structure is characterized by two hydrophilic groups (sugar, carboxylic acid) on both ends with a hydrophobic moiety in the middle. We tested three different glycolipid molecules: C18:1 sophorolipids and single-glucose C18:1 and C18:0 glucolipids, all in their nonacetylated acidic form. Neither sophorolipids (too soluble) nor C18:0 glucolipids (too insoluble) displayed myelin growth at room temperature (RT, 25 C). The glucolipid C18:1 (G-C18:1), on the other hand, showed dense myelin growth at RT below pH 7.0. Examining their growth rates, we find that they display a linear L $\alpha$ t (L, myelin length; t, time) growth rate, suggesting ballistic growth, distinctly different from the L $\alpha$ t^(1/2) dependence, characterizing diffusive growth such as what occurs in more conventional phospholipids. These results offer some insight into lipidic mesophases arising from a previously unexplored class of amphiphiles with potential applications in the field of drug delivery

Chemical Modification of Xylan

Our study is part of the general context of valuing by-products from the wood industry, which consists of the chemical modification of xylan by synthesis of branched copolymers such as xylan-g-PLLA. The used xylan is extracted from chestnut and 4-dimethylaminopyridine (DMAP) is the catalyst. In fact, the synthesis of xylan-graft-poly (L-lactide) copolymer starting from natural and renewable resource products xylan and L-lactide is performed under different conditions. The results of the grafting reaction are unfavorable due to longer time because of depolymerization reactions. Another result is the solubility and insolubility of the copolymers synthesized in water. This first result indicates that there is a change in the properties of xylan. Moreover, the solubility of the xylan-g-PLLA copolymers is different from one study to another. Grafting of PLLA onto xylan was confirmed by Fourier transform infrared (FT-IR) and 1HNMR analyzes. The dynamic mechanical analysis showed that the xylan-g-PLLA plastic materials have interesting thermomechanical properties

Design and synthesis of triphenylphosphonium-porphyrin@xylan nanoparticles for anticancer photodynamic therapy

Most photosensitizers (PS) suffer from a lack of water solubility and from a low selectivity toward tumor cells. Delivery systems using nanoparticles make it possible to improve PS water solubility, and also tumor targeting via the enhanced permeability and retention (EPR) effect. Among the organelles, mitochondria are attractive target sites for drug-delivery strategies since they perform a variety of key cellular processes. Our study was aimed at synthesizing nanoparticles consisting of xylan-carrying porphyrins attached to a triphenylphosphonium moiety, in order to enhance the PDT effect through mitochondrial targeting. Hybrid nanoparticles were designed that consisted of a silica core coated with xylan substituted with porphyrin derivatives carrying a triphenylphosphonium moiety. These hybrid nanoparticles have been constructed, along with their counterparts devoid of silica core, taking into consideration the controversy surrounding the use of silica nanoparticles. Phototoxicity experiments, conducted against the HCT-116 and HT-29 colorectal cancer cell lines, showed that nanoparticles with porphyrins bearing a triphenylphosphonium moiety exhibited an enhanced photocytotoxic effect in comparison with free porphyrin or nanoparticles with porphyrins without the triphenylphosphonium moiety

Design and synthesis of triphenylphosphonium-porphyrin@xylan nanoparticles for anticancer photodynamic therapy

Most photosensitizers (PS) suffer from a lack of water solubility and from a low selectivity toward tumor cells. Delivery systems using nanoparticles make it possible to improve PS water solubility, and also tumor targeting via the enhanced permeability and retention (EPR) effect. Among the organelles, mitochondria are attractive target sites for drug-delivery strategies since they perform a variety of key cellular processes. Our study was aimed at synthesizing nanoparticles consisting of xylan-carrying porphyrins attached to a triphenylphosphonium moiety, in order to enhance the PDT effect through mitochondrial targeting. Hybrid nanoparticles were designed that consisted of a silica core coated with xylan substituted with porphyrin derivatives carrying a triphenylphosphonium moiety. These hybrid nanoparticles have been constructed, along with their counterparts devoid of silica core, taking into consideration the controversy surrounding the use of silica nanoparticles. Phototoxicity experiments, conducted against the HCT-116 and HT-29 colorectal cancer cell lines, showed that nanoparticles with porphyrins bearing a triphenylphosphonium moiety exhibited an enhanced photocytotoxic effect in comparison with free porphyrin or nanoparticles with porphyrins without the triphenylphosphonium moiety

Synthèse et caractérisation de nouvelles porphyrines glucolysées peptidiques à motif RGD en vue de leur application en photothérapie dynamique

Certaines porphyrines et analogues sont utilisés comme photosensibilisateurs en photothérapie dynamique des cancers. Les porphyrines glucosylées sont, dans ce domaine particulièrement intéressantes. En outre, il est connu que les cellules endothéliales constitutives de la néovascularisation tumorale, ainsi que certaines cellules cancéreuses, surexpriment l'intégrine aVb3. Cette glycoprotéine transmembranaire est capable de se lier aux protéines de la matrice extracellulaire par l'intermédiaire de la séquence peptidique Arginine-Glycine-Acide Aspartique (RGD). Avec pour finalité leur application en photothérapie anticancéreuse, nous avons mis au point, au cours de ce travail, la synthèse de nouvelles méso-arylglucosylporphyrines portant le motif peptidique RGD. Ainsi, nous avons dans un premier temps synthétisé en phase solide une première famille de composés constituée de tritolyl et triglucosylporphyrines portant le tripeptide RGD fixé en position ortho ou para d'un groupement phényle. Par la suite, nous avons synthétisé une deuxième série de photosensibilisateurs portant un pentapeptide cyclique comportant la séquence RGD, cyclisé par réaction de métathèse sur support solide. Nous avons également formé par réaction de métathèse en phase solide un dimère de méso-arylglucosylporphyrines liées par un pont peptidique RGD. Tous les composés synthétisés ont été caractérisés par spectroscopie UV-Visible, RMN et spectrométrie de masse MALDI. De plus, certains de ces composés produisent de l'oxygène singulet et une étude préliminaire d'activité biologique a été réalisée sur la lignée promyélocytaire K562. Les résultats obtenus indiquent que cette nouvelle classe de photosensibilisateurs semble prometteuse pour la thérapie photodynamiqueLIMOGES-BU Sciences (870852109) / SudocSudocFranceF

Synthesis of novel phosphonated tripodal ligands for actinides chelation therapy

0040-4039Efficient synthetic routes for preparation of a new family of aldehyde-bisphosphonate conjugates were presented. These compounds appeared as promising intermediates for incorporation of bisphosphonate moiety in various substrates under mild conditions. We report here a first application to the synthesis of a series of three phosphonated tripods designed for actinides chelation therapy

Pseudo porphyrinyl amino acids based on 1,3,5-triazine scaffold: New tools for the synthesis of peptidic porphyrins

International audienc

An efficient route to dimeric porphyrin-RGD peptide conjugates via olefin metathesis.

International audienceWe report the efficient use of cross-metathesis for the solid-phase synthesis of a porphyrin dimer containing as a spacer a pentapeptide moiety with RGD sequence. Such compound appears as a promising candidate for application in PDT

Measuring the bending rigidity of microbial glucolipid (biosurfactant) bioamphiphile self-assembled structures by neutron spin-echo (NSE): interdigitated vesicles, lamellae and fibers

Bending rigidity, k, is classically measured for lipid membranes to characterize their nanoscale mechanical properties as a function of composition. Widely employed as a comparative tool, it helps understanding the relationship between the lipid’s molecular structure and the elastic properties of its corresponding bilayer. Widely measured for phospholipid membranes in the shape of giant unilamellar vesicles (GUVs), bending rigidity is determined here for three self-assembled structures formed by a new biobased glucolipid bioamphiphile, rather associated to the family of glycolipid biosurfactants than phospholipids. In its oleyl form, glucolipid G-C18:1 can assemble into vesicles or crystalline fibers, while in its stearyl form, glucolipid G-C18:0 can assemble into lamellar gels. Neutron spin-echo (NSE) is employed in the q-range between 0.3 nm-1 (21 nm) and 1.5 nm-1 (4.1 nm) with a spin-echo time in the range of up to 500 ns to characterize the bending rigidity of three different structures (Vesicle suspension, Lamellar gel, Fiber gel) solely composed of a single glucolipid. The low (k= 0.30 ¬± 0.04 kbT) values found for the Vesicle suspension and high values found for the Lamellar (k= 130 ± 40 kbT) and Fiber gels (k= 900 ± 500 kbT) are unusual when compared to most phospholipid membranes. By attempting to quantify for the first time the bending rigidity of self-assembled bioamphiphiles, this work not only contributes to the fundamental understanding of these new molecular systems, but it also opens new perspectives in their integration in the field of soft materials