Sami Halila

Oligosaccharide/Silicon-Containing Block Copolymers with 5 nm Features for Lithographic Applications

Block copolymers demonstrate potential for use in next-generation lithography due to their ability to self-assemble into well-ordered periodic arrays on the 3-100 nm length scale. The successful lithographic application of block copolymers relies on three critical conditions being met: high Flory-Huggins interaction parameters (χ), which enable formation of <10 nm features, etch selectivity between blocks for facile pattern transfer, and thin film self-assembly control. The present paper describes the synthesis and self-assembly of block copolymers composed of naturally derived oligosaccharides coupled to a silicon-containing polystyrene derivative synthesized by activators regenerated by electron transfer atom transfer radical polymerization. The block copolymers have a large χ and a low degree of polymerization (N) enabling formation of 5 nm feature diameters, incorporate silicon in one block for oxygen reactive ion etch contrast, and exhibit bulk and thin film self-assembly of hexagonally packed cylinders facilitated by a combination of spin coating and solvent annealing techniques. As observed by small angle X-ray scattering and atomic force microscopy, these materials exhibit some of the smallest block copolymer features in the bulk and in thin films reported to date.

A Brief and Informationally Rich Naming System for Oligosaccharide Motifs of Heteroxylans Found in Plant Cell Walls

The one-letter code system proposed here is a simple method to accurately describe structurally diverse oligosaccharides derived from heteroxylans. Substitutions or ‘molecular decoration(s)’ of main-chain d-xylosyl moieties are designated by unique letters. Hence, an oligosaccharide is described by a series of single letters, beginning with the non-reducing d-xylosyl unit. Superscripted numbers are used to indicate the linkage position(s) of main-chain substitution(s) and, where necessary, superscripted lowercase letter(s) indicate the nature of non-glycosidic groups (e.g., methyl, acetyl, or phenolic derivative moieties) that can be present on the substituents. Although relatively simple and practical to use, this abbreviated system lends itself to the naming of a large number of different combinations of structural building blocks and substituents. In its present state, this system is, therefore, adequate to name and differentiate all currently known complex oligosaccharides derived from heteroxylans and is sufficiently flexible to accommodate new structures as they become available.

Control of 10 nm scale cylinder orientation in self-organized sugar-based block copolymer thin films

The present paper describes the orientational control of 10 nm scale cylinders in sugar-based block copolymer thin films by simply varying the composition of the annealing co-solvent. The affinity of the block copolymer to the solvent vapor could be systematically adjusted in this way.

Redox-stimuli responsive micelles from DOX-encapsulating polycaprolactone-g-chitosan oligosaccharide

Chitosan-based amphiphilic graft copolymers are commonly obtained by modification of chitosan backbones with synthetic polymers hampering both bioactivity and biodegradability. In this work, we report the preparation of a series of chitosan oligosaccharide-grafted copolymers (PCL-g-COs) from coupling reactions between azide-pendent polycaprolactones (PCL-N3) and reducing-end alkynyl-modified chitosan oligosaccharides (COs-alkynyl). The resulting PCL-g-COs self-organized in water into nanoscale micelles (Rh<20 nm) having a COs shell and a PCL core. Locking of the core-micelles structure employing a disulfide-containing bis-alkyne cross-linker resulted in the formation of nano-vehicles which can be degraded in response to physiological (redox) stimuli. This feature was advantageously exploited to preferentially release an anticancer drug, doxororubicin, in response to the intracellular glutathione level.

Sulfated glycosaminoglycan-based block copolymer: preparation of biocompatible chondroitin sulfate-b-poly(lactic acid) micelles.

Despite a growing interest in amphiphilic polysaccharide-based diblock copolymers as functional polymeric drug delivery nanosystems, biologically relevant sulfated glycosaminoglycan systems were not yet investigated. Here, we report the synthesis and the self-assembly properties in water of chondroitin sulfate-b-poly(lactic acid) (CS-b-PLA(n)). The CS-b-PLA(n) were synthesized using click-grafting onto method implying reducing-end alkynation of low-molecular weight depolymerized CS (M(w) = 5000 g·mol(-1)) and azide-terminated functionalization of PLAn (M(w) = 6500 g·mol(-1) (n = 46) and M(w) = 1700 g·mol(-1) (n = 20)). The diblock copolymer self-assembled in water giving rise to spherical micelles that were characterized in solution using dynamic/static light scattering and at dry state by TEM technique. In vitro assays on healthy cells showed that at high concentrations, up to 10 μg·mL(-1), CS-b-PLA(n) were noncytotoxic. Those preliminary studies are promising in the perspective to use them as biocompatible nanovehicles for anticancer drug delivery.

Xyloglucan-block-Poly(ϵ-Caprolactone) Copolymer Nanoparticles Coated with Chitosan as Biocompatible Mucoadhesive Drug Delivery System

The development of novel xyloglucan-block-poly(ϵ-caprolactone) (XGO-b-PCL) nanoparticles coated with the mucoadhesive polysaccharide chitosan is described. XGO-b-PCL nanoparticles show monodisperse size distribution (Rh  = 50 nm). Curcumin is successfully encapsulated within the PCL core within drug to polymer ratio of 1:5 (w/w). The coating of nanoparticles with chitosan results in an increased particle size and positive surface charge due to the polycation nature of the chitosan. Mucoadhesive properties of chitosan-coated nanoparticles are demonstrated by its exceptional ability to interact with mucin through electrostatic forces. Finally, in vitro studies show that curcumin-loaded nanoparticles exhibit higher cytotoxic effects against B16F10 melanoma cells than L929 fibroblast cells.

Oligosaccharide Carbohydrate Dielectrics toward High-Performance Non-volatile Transistor Memory Devices.

Oligosaccharides are one of the most promising biomaterials because they are abundant, renewable, diversified, and biosourced. The use of oligo- or polysaccharides for high-performance non-volatile organic field-effect-transistor memory is demonstrated herein. The charge-storage mechanism is attributed to charged hydroxyl groups that induce stronger hydrogen bonding, thus leading to the stabilization of trapped charges. This study reveals a promising future for green memory devices.

Preparation and enzymatic hydrolysis of nanoparticles made from single xyloglucan polysaccharide chain

In this work, polysaccharide nanoparticles based on tamarind seeds xyloglucan are prepared, analyzed in term of characteristic sizes and morphology, and degraded by the action of a glycoside-hydrolase. Obtained in an aqueous NaNO2 solution (0.1M), these unaggregated nanoparticles have a characteristic diameter of ca. 60 nm (DLS, AFM and TEM measures). They are not compact, but highly swollen and look like hyperbranched and dendrimer-like (soft sphere model) structures. This observation is coherent with the native structure of the xyloglucan macromolecules which are themselves branched. The enzymatic hydrolysis by cellulase of Trichoderma reesei of the xyloglucan nanoparticles is investigated. In particular, the apparent mass molecular weight drastically decreases meaning that the xyloglucan nanoparticles are effectively fully hydrolyzed by the endo-β-(1,4)-glucanase. Furthermore, we observe that the enzyme has to uncoil the nanoparticles before cutting the β-(1→4) bonds and digesting the xyloglucan.

A straightforward access to TMG-chitooligomycins and their evaluation as β-N-acetylhexosaminidase inhibitors

A chemo-biotechnological approach is reported for the synthesis of TMG-chitooligomycins, CO-n (NMe(3)). Their abilities to inhibit β-N-acetylhexosaminidases (HexNAcases), from Aspergillus oryzae (AoHex, fungi), Canavalia ensiformis (CeHex, plant) HexNAcases and a chitobiase from Serratia marcescens (SmCHB, bacteria) were studied and compared with their precursors CO-n (N). CO-n (NMe(3)) were revealed as potent inhibitors for AoHex and SmCHB with a proved chain length effect while CO-n (N) was a highly selective inhibitor of SmCHB. This route can be considered as the privileged way to produce easily and in large scale a wide range of size-defined chitooligosaccharide-based inhibitors to fine-tune the structure-activity relationships for inhibition of HexNAcases from various origins.

Oligosaccharide-based block copolymers: metal-free thiol-maleimide click conjugation and self-assembly into nanoparticles.

Amphiphilic oligosaccharide-based block copolymers (OBCPs) are able to self-assemble either into nanoparticles with biocompatible oligosaccharides corona in aqueous solution or in sub-nanopatterned thin-films originating from the high incompatibility between the different blocks. For these reasons, these biosourced OBCPs are valuable structures for applications in nanomedicine and nanoelectronics. Up to now, the synthesis of those OBCPs was obtained through grafting-onto method using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). However, complete removal of metal catalyst residues from the resultant copolymer chains is critical and hampers electronic and biomedical applications. In this study, we report an efficient and convenient metal-free click chemistry approach consisting in coupling thiol-containing oligosaccharide blocks to maleimide-terminated polystyrenes. Upon self-assembly in water, spherical micelles of similar size than those obtained by Cu(I)-catalyzed azide-alkyne cycloaddition were formed as evidenced using dynamic light scattering and transmission electron microscopy techniques.