Metallic Nanoparticles Adsorbed at the Pore Surface of Polymers with Various Porous Morphologies: Toward Hybrid Materials Meant for Heterogeneous Supported Catalysis.

Hybrid materials consisting of metallic nanoparticles (NPs) adsorbed on porous polymeric supports have been the subject of intense research for many years. Such materials indeed gain from intrinsic properties, e.g., high specific surface area, catalytic properties, porous features, etc., of both components. Rational design of such materials is fundamental regarding the functionalization of the support surface and thus the interactions required for the metallic NPs to be strongly immobilized at the pore surface. Herein are presented some significant scientific contributions to this rapidly expanding research field. This contribution will notably focus on various examples of such hybrid systems prepared from porous polymers, whatever the morphology and size of the pores. Such porous polymeric supports can display pores with sizes ranging from a few nanometers to hundreds of microns while pore morphologies, such as spherical, tubular, etc., and/or open or closed, can be obtained. These systems have allowed some catalytic molecular reactions to be successfully undertaken, such as the reduction of nitroaromatic compounds or dyes, e.g., methylene blue and Eosin Y, boronic acid-based C-C homocoupling reactions, but also cascade reactions consisting of two catalytic reactions achieved in a row.

Contribution of the "Click Chemistry" Toolbox for the Design, Synthesis, and Resulting Applications of Innovative and Efficient Separative Supports: Time for Assessment.

The last two decades have seen the rapid expansion of click chemistry methodology in various domains closely related to organic chemistry. It has notably been widely developed in the area of surface chemistry, mainly because of the high-yielding character of reactions of the "click" type. Especially, this powerful chemical reaction toolbox has been adapted to the preparation of stationary phases from the corresponding chromatographic supports. A plethora of selectors can thus be immobilized on either organic, inorganic, or hybrid stationary phases that can be used in different chromatographic modes. This review first highlights the few different chemical ligation strategies of the "click" type that are up to now mainly devoted to the development of functionalized supports for separation sciences. Then, it gives in a second part an up-to-date survey of the different studies dedicated to the preparation of click chemistry-based chromatographic supports while highlighting the powerful and versatile character of the "click" ligation strategy for the design, synthesis, and developments of more and more complex systems that can find promising applications in the area of analytical sciences, in domains as varied as enantioselective separation, glycomics, proteomics, genomics, metabolomics, etc.

Wood-Mimicking Bio-Based Biporous Polymeric Materials with Anisotropic Tubular Macropores.

Understanding physical phenomena related to fluid flow transport in plants and especially through wood is still a major challenge for the scientific community. To this end, we have focused our attention on the design of wood-mimicking polymeric architectures through a strategy based on the double porogen templating approach which relies on the use of two distinct types of porogens, namely aligned nylon threads and a porogenic solvent, to produce macro- and nanoporosity levels, respectively. A bio-based phenolic functional monomer, i.e., vanillin methacrylate, was employed to mimic either hard wood or soft wood. Upon free-radical polymerization with a crosslinking agent in the presence of both types of porogenic agents, followed by their removal, biporous materials with anistotropic tubular macropores surrounded by a nanoporous matrix were obtained. They were further fully characterized in terms of porosity and chemical composition via mercury intrusion porosimetry, scanning electron microscopy and X-ray microtomography. It was demonstrated that the two porosity levels could be independently tuned by varying structural parameters. Further, the possibility to chemically modify the pore surface and thus to vary the material surface properties was successfully demonstrated by reductive amination with model compounds via Raman spectroscopy and water contact angle measurements.

Development of Latent Fingerprints via Aryldiazonium Tetrachloroaurate Salts on Copper Surfaces: An XPS Study.

Surface studies of developed fingerprints have aided in the elimination of criminal cases before moving to the court. The combination of X-ray photoelectron spectroscopy (XPS) with the aryldiazonium gold(III), 4-O2NC6H4N2+AuCl4-, surface modifier has been shown to be a novel approach in latent fingerprint detection and development for the quantification of film elements. The robust gold-aryl film was developed on the reducing chemicals excreted in the sebaceous fingerprints without the need for external stimuli and at a lesser extent after contacting the free metal surface. The concurrent reduction of the diazonium functional group and gold(III) from [AuCl4]- developed a robust gold-aryl film, which showed increasing gold(0) quantity in the time range of 30-120 min over copper coins and model flat sheets. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) support the presence of reduced gold on the top of the latent fingerprints and the presence of CuO resulting from the reaction of the diazonium salt with copper metal. This research combines the quantification of deposits using XPS, a surface-sensitive technique for chemical analysis, in addition to surface imaging.

Synergistic actions of mixed small and large pores for capillary absorption through biporous polymeric materials.

Water absorption in porous media is an important process involved in numerous materials for various applications, such as in the building industry, food processing and bioengineering. Designing new materials with appropriate absorption properties requires an understanding of how absorption behavior depends on both the material's morphology and the properties of the solid matrix, i.e. hydrophilic/hydrophobic nature and swelling/deformation properties. Although the basic principles of imbibition are well-known for simple porous systems, much less is known about absorption in complex porous systems, in particular those containing several coexisting porous phases, such as wood for example. Here, water absorption is studied for model porous organic materials exhibiting several degrees of hydrophobicity and two pore size levels, either as monoporous materials (large or small pores) or as biporous materials (mixed large and small pores). The interconnected biporous structure is designed via a double porogen templating approach using cubic sodium chloride particles as templates for the generation of the larger pore size (250-400 µm) and i-PrOH as a porogenic solvent for the smaller pore size (2-5 µm). While absorption for the small pore material is well described by the classical Washburn theory, the large pore material shows a drastic reduction in the imbibition rate. This behavior is attributed to the slow breakthrough mechanism for the water interface at sharp edge connections between pores. Remarkably, this slow regime is suppressed for the biporous material and the imbibition rate is even higher than the sum of rates obtained for its monoporous counterparts, which highlights the synergistic action of mixed small and large pores.

Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer's disease-like transgenic mouse model.

Alzheimer's disease (AD) is a neurodegenerative disorder related, in part, to the accumulation of amyloid-ß peptide (Aß) and especially the Aß peptide 1-42 (Aß1-42). The aim of this study was to design nanocarriers able to: (i) interact with the Aß1-42 in the blood and promote its elimination through the "sink effect" and (ii) correct the memory defect observed in AD-like transgenic mice. To do so, biodegradable, PEGylated nanoparticles were surface-functionalized with an antibody directed against Aß1-42. Treatment of AD-like transgenic mice with anti-Aß1-42-functionalized nanoparticles led to: (i) complete correction of the memory defect; (ii) significant reduction of the Aß soluble peptide and its oligomer level in the brain and (iii) significant increase of the Aß levels in plasma. This study represents the first example of Aß1-42 monoclonal antibody-decorated nanoparticle-based therapy against AD leading to complete correction of the memory defect in an experimental model of AD.

Porous Gold Nanoparticle-Decorated Nanoreactors Prepared from Smartly Designed Functional Polystyrene-block-Poly(d,l-Lactide) Diblock Copolymers: Toward Efficient Systems for Catalytic Cascade Reaction Processes.

Original porous catalytic supports can be engineered via an effective and straightforward synthetic route to polystyrene-block-poly(d,l-lactide) diblock copolymer precursors displaying an acid-cleavable acetal junction between both blocks. To this purpose, we synthesized an acetal-containing heterodifunctional initiator, thus enabling to combine two different polymerization methods, i.e., first atom transfer radical polymerization (ATRP) of styrene, and then ring-opening polymerization (ROP) of d,l-lactide. Thanks to the labile nature of the acetal junction, oriented porous frameworks could be obtained upon trifluoroacetic acid-mediated cleavage of the latter, after orientation of the block copolymer nanodomains by solvent vapor annealing. The resulting porous materials bearing a reactive aldehyde function at the pore surface allowed for further chemical modification via reductive amination with amino-containing compounds, such as tetraethylenepentamine, thus leading to amine-functionalized porous polystyrene. In situ generated gold nanoparticles could then be immobilized within such functionalized porous nanoreactors, and these hybrid materials could find interesting applications in heterogeneous supported catalysis. In this regard, model catalytic reactions, including C-C homocoupling of benzeneboronic acid derivatives, hydride-mediated reduction of nitroaromatic compounds, and especially unprecedented "one-pot" cascade reactions consisting of the latter consecutive reactions from 3-nitrobenzeneboronic acid, were successfully monitored by different chromatographic and spectroscopic techniques.

Oleylamine as a beneficial agent for the synthesis of CoFe2O4 nanoparticles with potential biomedical uses.

The multifunctional role of oleylamine (OAm) as a versatile and flexible reagent in synthesis as well as a desired surface ligand for the synthesis of CoFe2O4 nanoparticles (NPs) is described. CoFe2O4 NPs were prepared by a facile, reproducible and scalable solvothermal approach in the presence of pure OAm. By monitoring the volume of OAm, different shapes of NPs, spherical and truncated, were formed. The syntheses led to high yields of monodispersed and considerably small (9-11 nm) CoFe2O4 NPs with enhanced magnetization (M(s) = 84.7-87.5 emu g(-1)). The resulting hydrophobic CoFe2O4 NPs were easily transferred to an aqueous phase through the formation of reverse micelles between the hydrophobic chains of OAm and cetyltrimethylammonium bromide (CTAB) and transverse relaxivities (r2) were measured. The spherical NPs had a greater effect on water proton relaxivity (r2 = 553 mM(-1) s(-1)) at an applied magnetic field of 11.7 T. The NPs became fluorescent probes by exploiting the presence of the double bond of OAm in the middle of the molecule; a thiol-ene "click" reaction with the fluorophore bovine serum albumin (FITC-BSA) was achieved. The labeled/biofunctionalized CoFe2O4 NPs interacted with cancer (HeLa and A549) and non-cancer cell lines (MRC5 and dental MSCS) and cell viability was estimated. A clear difference of toxicity between the cancer and non-cancer cells was observed while low cytotoxicity in living cells was supported. Confocal laser microscopy showed that NPs entered the cell membranes and were firstly localized close to them provoking a membrane expansion and were further accumulated perinuclearly without entering the nuclei.

Facile synthesis of multicompartment micelles based on biocompatible poly(3-hydroxyalkanoate).

In this paper, a straightforward method to produce poly(3-hydroxyalkanoate)-based multicompartment micelles (MCMs) is presented. Thiol-ene addition is used to graft sequentially perfluorooctyl chains and poly(ethylene glycol) oligomers onto poly(3-hydroxyoctanoate-co-hydroxyundecenoate) oligomers backbone. Well-defined copolymers are obtained as shown by ¹H NMR and size-exclusion chromatography. After nanoprecipitation in water, novel PHA-based MCMs are evidenced by cryo-transmission electron microscopy. Moreover, the cytocompatibility of MCMs is demonstrated in vitro via cell viability assay.

Versatile and efficient targeting using a single nanoparticulate platform: application to cancer and Alzheimer's disease.

A versatile and efficient functionalization strategy for polymeric nanoparticles (NPs) has been reported and successfully applied to PEGylated, biodegradable poly(alkyl cyanoacrylate) (PACA) nanocarriers. The relevance of this platform was demonstrated in both the fields of cancer and Alzheimer's disease (AD). Prepared by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and subsequent self-assembly in aqueous solution of amphiphilic copolymers, the resulting functionalized polymeric NPs exhibited requisite characteristics for drug delivery purposes: (i) a biodegradable core made of poly(alkyl cyanoacrylate), (ii) a hydrophilic poly(ethylene glycol) (PEG) outer shell leading to colloidal stabilization, (iii) fluorescent properties provided by the covalent linkage of a rhodamine B-based dye to the polymer backbone, and (iv) surface functionalization with biologically active ligands that enabled specific targeting. The construction method is very versatile and was illustrated by the coupling of a small library of ligands (e.g., biotin, curcumin derivatives, and antibody), resulting in high affinity toward (i) murine lung carcinoma (M109) and human breast cancer (MCF7) cell lines, even in a coculture environment with healthy cells and (ii) the ß-amyloid peptide 1-42 (Aß(1-42)), believed to be the most representative and toxic species in AD, both under its monomeric and fibrillar forms. In the case of AD, the ligand-functionalized NPs exhibited higher affinity toward Aß(1-42) species comparatively to other kinds of colloidal systems and led to significant aggregation inhibition and toxicity rescue of Aß(1-42) at low molar ratios.

PEGylated nanoparticles bind to and alter amyloid-beta peptide conformation: toward engineering of functional nanomedicines for Alzheimer's disease.

We have demonstrated that the polyethylene glycol (PEG) corona of long-circulating polymeric nanoparticles (NPs) favors interaction with the amyloid-beta (Aß(1-42)) peptide both in solution and in serum. The influence of PEGylation of poly(alkyl cyanoacrylate) and poly(lactic acid) NPs on the interaction with monomeric and soluble oligomeric forms of Aß(1-42) peptide was demonstrated by capillary electrophoresis, surface plasmon resonance, thioflavin T assay, and confocal microscopy, where the binding affected peptide aggregation kinetics. The capture of peptide by NPs in serum was also evidenced by fluorescence spectroscopy and ELISA. Moreover, in silico and modeling experiments highlighted the mode of PEG interaction with the Aß(1-42) peptide and its conformational changes at the nanoparticle surface. Finally, Aß(1-42) peptide binding to NPs affected neither complement activation in serum nor apolipoprotein-E (Apo-E) adsorption from the serum. These observations have crucial implications in NP safety and clearance kinetics from the blood. Apo-E deposition is of prime importance since it can also interact with the Aß(1-42) peptide and increase the affinity of NPs for the peptide in the blood. Collectively, our results suggest that these engineered long-circulating NPs may have the ability to capture the toxic forms of the Aß(1-42) peptide from the systemic circulation and potentially improve Alzheimer's disease condition through the proposed "sink effect".

Multifunctional Giant Amphiphiles via simultaneous copper(I)-catalyzed azide-alkyne cycloaddition and living radical polymerization.

A novel class of chemically addressable, multifunctional Giant Amphiphiles was synthesized in excellent yields and polydispersity following simultaneous or sequential living radical polymerization and the click, copper(I)-catalysed azide-alkyne cycloaddition (CuAAC). This new approach allows chemical tailoring of the biomacromolecules and in situ formation of nanocontainers.

Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells.

BACKGROUND: Because of the described hazards related to inhalation of manufactured nanoparticles, we investigated the lung toxicity of biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticles displaying various surface properties on human bronchial Calu-3 cells. METHODS: Positively and negatively charged as well as neutral nanoparticles were tailored by coating their surface with chitosan, Poloxamer, or poly (vinyl alcohol), respectively. Nanoparticles were characterized in terms of size, zeta potential, and surface chemical composition, confirming modifications provided by hydrophilic polymers. RESULTS: Although nanoparticle internalization by lung cells was clearly demonstrated, the cytotoxicity of the nanoparticles was very limited, with an absence of inflammatory response, regardless of the surface properties of the PLGA nanoparticles. CONCLUSION: These in vitro results highlight the safety of biodegradable PLGA nanoparticles in the bronchial epithelium and provide initial data on their potential effects and the risks associated with their use as nanomedicines.

Biodegradable nanoparticles meet the bronchial airway barrier: how surface properties affect their interaction with mucus and epithelial cells.

Despite the wide interest raised by lung administration of nanoparticles (NPs) for the treatment of various diseases, little information is available on their effect toward the airway epithelial barrier function. In this study, the potential damage of the pulmonary epithelium upon exposure to poly(lactide-co-glycolide) (PLGA) NPs has been assessed in vitro using a Calu-3-based model of the bronchial epithelial barrier. Positively and negatively charged as well as neutral PLGA NPs were obtained by coating their surface with chitosan (CS), poloxamer (PF68), or poly(vinyl alcohol) (PVA). The role of NP surface chemistry and charge on the epithelial resistance and mucus turnover, using MUC5AC as a marker, was investigated. The interaction with mucin reduced the penetration of CS- and PVA-coated NPs, while the hydrophilic PF68-coated NPs diffused across the mucus barrier leading to a higher intracellular accumulation. Only CS-coated NPs caused a transient but reversible decrease of the trans-epithelial electrical resistance (TEER). None of the NP formulations increased MUC5AC mRNA expression or the protein levels. These in vitro results highlight the safety of PLGA NPs toward the integrity and function of the bronchial airway barrier and demonstrate the crucial role of NP surface properties to achieve a controlled and sustained delivery of drugs via the pulmonary route.

Colloidal properties of biodegradable nanoparticles influence interaction with amyloid-ß peptide.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the extracellular deposition of amyloid-ß peptides (Aß). During the past few years, promising approaches based on nanotechnologies have emerged to alter Aß aggregation and its related toxicity. This study aims to investigate the influence of the nanoparticle colloidal properties over the interaction with Aß peptide 1-42 (Aß(1-42)). Using capillary electrophoresis with laser-induced fluorescence detection, it was shown that biodegradable poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanoparticles were able to interact with Aß(1-42) peptide leading to its uptake in rather short time periods. In addition, we highlighted the crucial role of the nanocarrier colloidal properties on the uptake kinetics. Whereas nanoparticles stabilized by sodium cholate (lower size and higher negative surface charge) gave optimum uptake kinetics, nanoparticles stabilized with others surfactants presented lower interactions. In contrast, PEG density seemed to have no influence on the interaction when sodium cholate was used for the preparation. This study intends to give new insights into Aß(1-42) peptide interaction with nanoparticulate systems by helping to determine suitable nanoparticle characteristics regarding forthcoming therapeutic strategies against AD.

Nanotechnologies for Alzheimer's disease: diagnosis, therapy, and safety issues.

Alzheimer's disease (AD) represents the most common form of dementia worldwide, affecting more than 35 million people. Advances in nanotechnology are beginning to exert a significant impact in neurology. These approaches, which are often based on the design and engineering of a plethora of nanoparticulate entities with high specificity for brain capillary endothelial cells, are currently being applied to early AD diagnosis and treatment. In addition, nanoparticles (NPs) with high affinity for the circulating amyloid-ß (Aß) forms may induce "sink effect" and improve the AD condition. There are also developments in relation to in vitro diagnostics for AD, including ultrasensitive NP-based bio-barcodes, immunosensors, as well as scanning tunneling microscopy procedures capable of detecting Aß(1-40) and Aß(1-42). However, there are concerns regarding the initiation of possible NP-mediated adverse events in AD, thus demanding the use of precisely assembled nanoconstructs from biocompatible materials. Key advances and safety issues are reviewed and discussed.

Selegiline-functionalized, PEGylated poly(alkyl cyanoacrylate) nanoparticles: Investigation of interaction with amyloid-ß peptide and surface reorganization.

Alzheimer's disease (AD) is a neurodegenerative disorder for which the research of new treatments is highly challenging. Since the fibrillogenesis of amyloid-ß peptide 1-42 (Aß(1-42)) peptide is considered as a major cause of neuronal degeneration, specific interest has been focused on aromatic molecules for targeting this peptide. In this paper, the synthesis of selegiline-functionalized and fluorescent poly(alkyl cyanoacrylate) nanoparticles (NPs) and their evaluation for the targeting of the Aß(1-42) peptide are reported. The synthetic strategy relied on the design of amphiphilic copolymers by tandem Knoevenagel-Michael addition of cyanoacetate derivatives, followed by their self-assembly in aqueous solutions to give the corresponding NPs. Different cyanoacetates were used: (i) hexadecyl cyanoacetate (HDCA) to form the hydrophobic core of the NPs; (ii) rhodamine B cyanoacetate (RCA) for fluorescent purposes; (iii) methoxypoly(ethylene glycol) cyanoacetate (MePEGCA) for stealth properties and (iv) selegiline-poly(ethylene glycol) cyanoacetate (SelPEGCA) to obtain the desired functionality. Two different amphiphilic copolymers were synthesized, a selegiline-containing copolymer, P(MePEGCA-co-SelPEGCA-co-HDCA), and a rhodamine-labelled counterpart, P(MePEGCA-co-RCA-co-HDCA), further blended at variable ratios to tune the amount of selegiline moieties displayed at the surface of the NPs. Optimal formulations involving the different amphiphilic copolymers were determined by the study of the NP colloidal characteristics. Interestingly, it was shown that the zeta potential value of the selegiline-functionalized nanoparticles dramatically decreased, thus emphasizing a significant modification in the surface charge of the nanoparticles. Capillary electrophoresis has then been used to test the ability of the selegiline-functionalized NPs to interact with the Aß(1-42) peptide. In comparison with non functionalized NPs, no increase of the interaction between these functionalized NPs and the monomeric form of the Aß(1-42) peptide was observed, thus highlighting the lack of availability of the ligand at the surface of the nanoparticles. A mechanism explaining this result has been proposed and was mainly based on the burial of the hydrophobic selegiline ligand within the nanoparticles core.

New method based on capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) to monitor interaction between nanoparticles and the amyloid-ß peptide.

A novel application of capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) was proposed to efficiently detect and monitor the interaction between polymeric nanoparticles and the ß-Amyloid peptide (Aß(1-42)), a biomarker for Alzheimer's Disease (AD), at concentrations close to physiological conditions. The CE-LIF method allowed the interaction between PEGylated poly(alkyl cyanoacrylate) nanoparticles (NPs) and the soluble Aß(1-42) peptide monomers to be highlighted. These results were confirmed by surface plasmon resonance (SPR) and confocal laser scanning microscopy (CLSM). Whereas SPR showed an interaction between the NPs and the Aß(1-42) peptide, CLSM allowed the formation of large aggregates/assemblies at high NP and peptide concentrations to be visualized. All these results suggested that these nanoparticles could bind the Aß(1-42) peptide and influence its aggregation kinetics. Interestingly, the non-PEGylated poly(alkyl cyanoacrylate) NPs did not alter the aggregation kinetics of the Aß(1-42) peptide, thus emphasizing the high level of discrimination of the CE-LIF method with respect to NPs.

Design of fluorescently tagged poly(alkyl cyanoacrylate) nanoparticles for human brain endothelial cell imaging.

Rhodamine B-tagged poly(alkyl cyanoacrylate) amphiphilic copolymers have been synthesised, characterised and successfully used to prepare fluorescent nanoparticles for human brain endothelial cell imaging, allowing their uptake and intracellular trafficking to be finely observed.