Surface-induced nucleation strategies: seeking symmetries between self-assembly of heteronucleants and crystals

The present paper presents the application of surfaces having defined and controlled attributes as heteronucleants for the crystallization of a model pharmaceutical molecule. The synthesis of the substrate was optimized in order to relate surface features to the crystallization outcome. Extremely flat and topographically uniform glass supports bearing amino and thiol head groups were successfully synthesized and characterized by means of contact angle, AFM and XPS analyses. Such surfaces were then used as supports for aspirin (ASA) crystallization in order to investigate their influence on nucleation kinetics. Compared to untreated glass, amino-functionalized glass was dramatically nucleation-active, whereas thiol-functionalized supports strongly repressed ASA heterogeneous nucleation. The promoting or inhibiting action towards the stabilization of ASA nuclei on a functionalized surface and their successive growth into crystals was therefore related to the chemistry of exposed head groups

Visible light assisted organosilane assembly on mesoporous silicon films and particles

Porous silicon (PSi) is a versatile matrix with tailorable surface reactivity, which allows the processing of a range of multifunctional films and particles. The biomedical applications of PSi often require a surface capping with organic functionalities. This work shows that visible light can be used to catalyze the assembly of organosilanes on the PSi, as demonstrated with two organosilanes: aminopropyl-triethoxy-silane and perfluorodecyl-triethoxy-silane. We studied the process related to PSi films (PSiFs), which were characterized by X-ray photoelectron spectroscopy (XPS), time of flight secondary ion mass spectroscopy (ToF-SIMS) and field emission scanning electron microscopy (FESEM) before and after a plasma patterning process. The analyses confirmed the surface oxidation and the anchorage of the organosilane backbone. We further highlighted the surface analytical potential of 13 C, 19 F and 29 Si solid-state NMR (SS-NMR) as compared to Fourier transformed infrared spectroscopy (FTIR) in the characterization of functionalized PSi particles (PSiPs). The reduced invasiveness of the organosilanization regarding the PSiPs morphology was confirmed using transmission electron microscopy (TEM) and FESEM. Relevantly, the results obtained on PSiPs complemented those obtained on PSiFs. SS-NMR suggests a number of siloxane bonds between the organosilane and the PSiPs, which does not reach levels of maximum heterogeneous condensation, while ToF-SIMS suggested a certain degree of organosilane polymerization. Additionally, differences among the carbons in the organic (non-hydrolyzable) functionalizing groups are identified, especially in the case of the perfluorodecyl group. The spectroscopic characterization was used to propose a mechanism for the visible light activation of the organosilane assembly, which is based on the initial photoactivated oxidation of the PSi matrixWe acknowledge MSC funding provided by the European Commission through FP7 grant THINFACE (ITN GA 607232) and by Ministerio de Economía y Competitividad through grant NANOPROST (RTC-2016-4776-1

A general and adaptive synthesis protocol for high-quality organosilane self‐assembled monolayers as tunable surface chemistry platforms for biochemical applications

The controlled modification of surface properties represents a pervasive requirement to be fulfilled when developing new technologies. In this paper, we propose an easy-to-implement protocol for the functionalization of glass with Self-Assembled Monolayers (SAMs). The adaptivity of the synthesis route was demonstrated by the controlled anchoring of thiol, amino, glycidyloxy, and methacrylate groups onto the glass surface. The optimization of the synthetic pathway was mirrored by extremely smooth SAMs (approx. 150 pm roughness), layer thickness comparable to the theoretical molecule length, absence of silane islands along the surface, quasi-unitary degree of packing, and tailored wettability and charge. The functionalization kinetics of two model silanes, 3-mercapto- and 3-amino-propyltrimethoxysilane, was determined by cross-comparing X-Ray Photoelectron Spectroscopy (XPS) and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) data. Our SAMs with tailored physico-chemical attributes will be implemented as supports for the crystallization of pharmaceuticals and biomolecules in upcoming studies. Here, the application to a small molecule drug model, namely aspirin, was discussed as proof of concept

Plasma Modification of PCL Porous Scaffolds Fabricated by Solvent Casting/Particulate Leaching for Tissue Engineering

This study points out how the plasma modification of PCL porous scaffolds, produced by Solvent Casting/Particulate Leaching, may enhance their biocompatibility. A C2H4/N2 plasma deposition followed by a H2 plasma treatment was used to increase the hydrophilicity of the whole scaffold to support osteoblast cell proliferation, both outside and inside the scaffold. A better cell growth was obtained on plasma modified scaffolds.JRC.I.4-Nanobioscience

Surface analysis of functionalized substrates for the nucleation and crystallization of pharmaceutical molecules

Nucleation represents the core of a variety of natural processes, ranging from ice crystal formation to protein aggregation, which can occur homogeneously or heterogeneously, depending on whether aggregation mechanism involves the presence of single or multiple phases. Recently, the role of external surface features on crystallization of active pharmaceutical ingredients (APIs) is being investigated by relating surface chemistry and morphology to nucleation kinetics and polymorph selection.1 Surface functionalization using SAMs has been largely investigated and applied to different substrates and constitutes one of the most robust methods available to obtain well controlled functionalized surfaces.2,3,,4 In the present study, the use of glass substrates functionalized with self-assembly of trimethoxysilanes differing for their head group chemistry for the nucleation and crystallization of small pharmaceutical molecules was investigated. Silane anchoring was achieved via wet chemistry-based route whilst systematic characterisation of morphology and chemistry was carried on in order to determine the influence of different parameters (Figure 1). Assessment of effective functionalization was carried out by means of contact angle and surface Z-potential analyses, whilst the surface chemistry of functionalized glass was probed using XPS and ToF SIMS. Lastly, AFM was adopted for the characterization of surface topography. High-quality monolayers carrying thiol, methacrylate and glycidyloxy exposed groups were successfully synthesized whereas in the case of amino-terminated silanes surface roughness dramatically increased and correlation between ideal and experimental elemental ratios characterizing the monolayer was not achieved. Nucleation and crystallization of biopharmaceutical molecules was also carried out by studying aspirin and paracetamol crystallization out in a thin-film solution deposited onto SAMs. Crystallization outcome was studied according to kinetic and thermodynamic aspects by optical microscopy, whilst crystal orientation and form were evaluated by means of X-Ray Diffractometry (XRD). Finally, preliminary results on nanostructurated surfaces will be also presented

Measuring Protein Structure and Stability of Protein-Nanoparticle Systems with Synchrotron Radiation Circular Dichroism

n/

Interaction of magnetic nanoparticles with U87MG cells studied by synchrotron radiation X-ray fluorescence techniques

International audienceSynchrotron radiation (SR) X-ray microscopy combined with X-ray fluorescence (XRF) microspectroscopy provides unique information that have pushed the frontiers of biological research, particularly when investigating intracellular mechanisms. This work reports an SR-XRF microspectroscopy investigation on the distribution and the potential toxicity of Fe 2 O 3 and CoFe 2 O 4 nanoparticles (NPs) in U87MG glioblastoma-astrocytoma cells. The U87MG cells exposed to NPs concentrations ranging from 5 to 250 mg/ml for 24 h were analyzed in order to monitor both morphological and chemical changes. The SR-XRF maps complemented with XRM absorption and phase contrast images have revealed different intracellular distribution patterns for the two nanoparticles types allowing different mechanism of toxicity to be deduced

A methodology to investigate heterogeneous oxidation of thermally aged cross-linked polyethylene by ToF-SIMS

Artificial ageing of polymeric insulation jackets is routinely performed in order to assess end-of-life material characteristics. Practical constraints including high temperatures/ short times ageing treatments lead to strong influence of diffusion-limited oxidation (DLO) resulting in unreliable life-time predictions. This study proposes a new experimental approach to the investigation of cable insulation ageing, exploiting analytical techniques capable of resolving chemistry at the length scale relevant for DLO (nano-microscale). When studying the potential effects of DLO using time of flight secondary ion mass spectrometry (ToF-SIMS) sample preparation becomes crucial. This paper presents the development of a methodology to generate suitable specimens to investigate the DLO effect using ToF-SIMS. A reference polymeric material has been thermally aged in various DLO conditions. Cross sections of aged samples were generated using three different methods. In order to assess the most suitable approach for this study, cross-section topography were scanned using a profilometer and the surface chemistry was investigated using ToF-SIMS together with multivariate analysis methods

TiO2@BSA nano-composites investigated through orthogonal multi-techniques characterization platform.

Abstract Biocompatible coating based on bovine serum albumin (BSA) was applied on two different TiO2 nanoparticles (aeroxide P25 and food grade E171) to investigate properties and stability of resulting TiO2@BSA composites, under the final perspective to create a "Safe-by-Design" coating, able to uniform, level off and mitigate surface chemistry related phenomena, as naturally occurring when nano-phases come in touch with proteins enriched biological fluids. The first step towards validating the proposed approach is a detailed characterization of surface chemistry with the quantification of amount and stability of BSA coating deposited on nanoparticles' surfaces. At this purpose, we implemented an orthogonal multi-techniques characterization platform, providing important information on colloidal behavior, particle size distribution and BSA-coating structure of investigated TiO2 systems. Specifically, the proposed orthogonal approach enabled the quantitative determination of bound and free (not adsorbed) BSA, a key aspect for the design of intentionally BSA coated nano-structures, in nanomedicine and, overall, for the control of nano-surface reactivity. In fact, the BSA-coating strategy developed and the orthogonal characterisation performed can be extended to different designed nanomaterials in order to further investigate the protein-corona formation and promote the implementation of BSA engineered coating as a strategy to harmonize the surface reactivity and minimize the biological impact

Modulation of surface bio-functionality by using gold nanostructures on protein repellent surfaces

The integration of gold nanoparticles (Au NPs) or nanostructures with special optical properties on solid surfaces has become a major research topic in the field of nanobiotechnology in particular for the development of new generation of multifunctional bioanalytical platforms. This has led to considerable research efforts for developing quick and direct nanofabrication methods capable of producing well-ordered 2D nanostructured arrays with tunable morphological, chemical and optical properties. In this paper, we propose a simple and fast nanofabrication method enabling the creation of Au NPs patterns on a non-adhesive and cell repellent plasma-deposited poly(ethyleneoxide) (PEO-like) coating. The immobilization of Au NPs on PEO-like coatings does not require any prior chemical modifications and is achieved by a straightforward and stable self-assembly technique. By varying the size and the concentration of the Au NPs it is possible to control the Au NPs density and spatial distribution on the PEO-like coated surface with direct effects on the bio-functionality of the surface. These nanostructured surfaces have been tested for protein bio-recognition analysis and as a cell culture platform. The developed nanostructured platform has many potential applications in the field of protein-nanoparticle and cell-nanoparticle interaction studies, nanotoxicology and bioengineering.JRC.I.4-Nanobioscience