Scaling Up Magnetic Nanobead Synthesis with Improved Stability for Biomedical Applications.

The growing interest in multifunctional nano-objects based on polymers and magnetic nanoparticles for biomedical applications motivated us to develop a scale-up protocol to increase the yield of polymeric magnetic nanobeads while aiming at keeping the structural features at optimal conditions. The protocol was applied to two different types of magnetic ferrite nanoparticles: the Mn-ferrite selected for their properties as contrast agents in magnetic resonance imaging and iron oxide nanostar shaped nanoparticles chosen for their heat performance in magnetic hyperthermia. At the same time, some experiments on surface functionalization of nanobeads with amino modified polyethyelene glycol (PEG) molecules have provided further insight into the formation mechanism of magnetic nanobeads and the need to cross-link the polymer shell to improve the stability of the beads, making them more suitable for further manipulation and use. The present work summarizes the most important parameters required to be controlled for the upscaling of nanobead synthesis in a bench protocol and proposes an alternative cross-linking strategy based on prefunctionalization of the polymer prior to the nanobead formation as a key parameter to improve the nanobead structural stability in solutions at different pHs and during surface functionalization.

Laser-Fabricated Fluorescent, Ligand-Free Silicon Nanoparticles: Scale-up, Biosafety, and 3D Live Imaging of Zebrafish under Development.

This work rationalizes the scalable synthesis of ultrasmall, ligand-free silicon nanomaterials via liquid-phase pulsed laser ablation process using picosecond pulses at ultraviolet wavelengths. Results showed that the irradiation time drives hydrodynamic NP size. Isolated, monodisperse Si-NPs are obtained at high yield (72%) using post-treatment process. The obtained Si-NPs have an average size of ∼10 nm (not aggregated) and display photoemission in the green spectral range. We directly characterized the ligand-free Si-NPs in a vertebrate animal (zebrafish) and assessed their toxicity during the development. In vivo assay revealed that Si-NPs are found inside in all the early life stages of embryos and larvae growth, showing that the biosafety of Si-NPs and malformation types are independent of the Si-NP dose. Si-NPs were directly imaged inside developing embryos by spinning disk-imaging technique with optical sectioning capability. We showed that Si-NPs can passively enter inside embryos by the pore canals of chorion, can diffuse in the circulatory system, i.e., blood vessel, and accumulate inside larvae midgut and yolk sac, and in the eye lens, indicating the crossing of the blood barrier.

Facile fabrication of bioactive ultra-small protein-hydroxyapatite nanoconjugates via liquid-phase laser ablation and their enhanced osteogenic differentiation activity.

Hydroxyapatite bioactive complexes are being increasingly recognized as effective available means in regenerative medicine. Conventional technologies for their synthesis have drawbacks from a synthetic standpoint, mainly requiring high temperatures and multi-step processes. Here, we show that ultra-small hydroxyapatite conjugated-nanoparticles (Ha-CNPs) can be obtained at room temperature by Pulsed Laser Ablation (PLA) directly in protein solution using picosecond pulses at near infrared wavelengths. The results showed that the nanoparticle size was driven by the concentration of the protein. Using this approach, we obtained aqueous soluble and ultra-small crystalline nanoparticles of ≈3 nm diameter coated with protein molecules (surface coverage ≈ 5.5 pmol cm-2; zeta potential ≈-33.5 mV). These nanoparticles showed low cytotoxicity in vitro compared to chemically synthesized nanoparticles, and revealed proliferative and osteoinductive effects on human bone marrow mesenchymal stem cells (hMSCs). The resulting enhanced cell osteogenic differentiation suggested that our PLA-based synthetic approach might be exploited in novel applications of regenerative medicine.

Direct surface modification of ligand-free silicon quantum dots prepared by femtosecond laser ablation in deionized water.

Amine-terminated, ultra-small silicon nanoparticles (Si-NPs) were prepared in one step avoiding the conventional chemical or thermal treatment of Si surface, by introducing organosilane in Si-NPs colloidal solution freshly prepared by ultra-fast laser ablation of silicon target in deionized water. Surface chemistry studies of Si-NPs conducted by Raman and Fourier infrared spectroscopy demonstrated the hydroxyl-terminated surface of Si-NPs. The reactivity of hydroxyl-terminated surface with aminopropyltriethoxysilane in aqueous solution was investigated. Electron microscopy, dynamic light scattering, infrared spectroscopy and stability studies confirmed the successful functionalization of Si-NPs leading to 5nm Si dots covered by aminopropyltriethoxysilane thick layer. Detailed infrared spectroscopy analysis of the Si-O-Si region as a function of immersion time revealed the formation of interfacial Si-O bonds between the organosilane and hydroxyl groups of the nanoparticles. The biocompatible Si nanostructure containing amine functional group prepared using a one-step green protocol opens the route for biomedical applications and successful translation into clinical setting, as bio-labels, contrast agents and vector delivery.

Extensive Characterization of Oxide-Coated Colloidal Gold Nanoparticles Synthesized by Laser Ablation in Liquid.

Colloidal gold nanoparticles are a widespread nanomaterial with many potential applications, but their aggregation in suspension is a critical issue which is usually prevented by organic surfactants. This solution has some drawbacks, such as material contamination and modifications of its functional properties. The gold nanoparticles presented in this work have been synthesized by ultra-fast laser ablation in liquid, which addresses the above issues by overcoating the metal nanoparticles with an oxide layer. The main focus of the work is in the characterization of the oxidized gold nanoparticles, which were made first in solution by means of dynamic light scattering and optical spectroscopy, and then in dried form by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and finally by surface potential measurements with atomic force microscopy. The light scattering assessed the nanoscale size of the formed particles and provided insight in their stability. The nanoparticles' size was confirmed by direct imaging in transmission electron microscopy, and their crystalline nature was disclosed by X-ray diffraction. The X-ray photoelectron spectroscopy showed measurements compatible with the presence of surface oxide, which was confirmed by the surface potential measurements, which are the novel point of the present work. In conclusion, the method of laser ablation in liquid for the synthesis of gold nanoparticles has been presented, and the advantage of this physical approach, consisting of coating the nanoparticles in situ with gold oxide which provides the required morphological and chemical stability without organic surfactants, has been confirmed by using scanning Kelvin probe microscopy for the first time.

Fabrication of hybrid nanocomposite scaffolds by incorporating ligand-free hydroxyapatite nanoparticles into biodegradable polymer scaffolds and release studies.

We report on the optical fabrication approach of preparing free-standing composite thin films of hydroxyapatite (HA) and biodegradable polymers by combining pulsed laser ablation in liquid and mask-projection excimer laser stereolithography (MPExSL). Ligand-free HA nanoparticles were prepared by ultrafast laser ablation of a HA target in a solvent, and then the nanoparticles were dispersed into the liquid polymer resin prior to the photocuring process using MPExSL. The resin is poly(propylene fumarate) (PPF), a photo-polymerizable, biodegradable material. The polymer is blended with diethyl fumarate in 7:3 w/w to adjust the resin viscosity. The evaluation of the structural and mechanical properties of the fabricated hybrid thin film was performed by means of SEM and nanoindentation, respectively, while the chemical and degradation studies were conducted through thermogravimetric analysis, and FTIR. The photocuring efficiency was found to be dependent on the nanoparticle concentration. The MPExSL process yielded PPF thin films with a stable and homogenous dispersion of the embedded HA nanoparticles. Here, it was not possible to tune the stiffness and hardness of the scaffolds by varying the laser parameters, although this was observed for regular PPF scaffolds. Finally, the gradual release of the hydroxyapatite nanoparticles over thin film biodegradation is reported.

Study on the productivity of silicon nanoparticles by picosecond laser ablation in water: towards gram per hour yield.

An investigation on the productivity of silicon nanoparticles by picosecond laser ablation in water is presented. A systematic experimental study is performed as function of the laser wavelength, fluence and ablation time. In case of ablation at 1064 nm silicon nanoparticles with a mean diameter of 40 nm are produced. Instead, ablation at 355 nm results in nanoparticles with a mean diameter of 9 nm for short ablation time while the mean diameter decreases to 3 nm at longer ablation time. An original model based on the in-situ ablation/photo-fragmentation physical process is developed, and it very well explains the experimental productivity findings. The reported phenomenological model has a general validity, and it can be applied to analyze pulsed laser ablation in liquid in order to optimize the process parameters for higher productivity. Finally, an outlook is given towards gram per hour yield of ultra-small silicon nanoparticles.

Influence of organic solvent on optical and structural properties of ultra-small silicon dots synthesized by UV laser ablation in liquid.

Ultra small silicon nanoparticles (Si-NPs) with narrow size distribution are prepared in a one step process by UV picosecond laser ablation of silicon bulk in liquid. Characterization by electron microscopy and absorption spectroscopy proves Si-NPs generation with an average size of 2 nm resulting from an in situ photofragmentation effect. In this context, the current work aims to explore the liquid medium (water and toluene) effect on the Si-NPs structure and on the optical properties of the colloidal solution. Si-NPs with high pressure structure (s.g. Fm3m) and diamond-like structure (s.g. Fd3m), in water, and SiC moissanite 3C phase (s.g. F4[combining macron]3m) in toluene are revealed by the means of High-Resolution TEM and HAADF-STEM measurements. Optical investigations show that water-synthesized Si-NPs have blue-green photoluminescence emission characterized by signal modulation at a frequency of 673 cm(-1) related to electron-phonon coupling. The synthesis in toluene leads to generation of Si-NPs embedded in the graphitic carbon-polymer composite which has intrinsic optical properties at the origin of the optical absorption and luminescence of the obtained colloidal solution.

Bioconjugated silicon quantum dots from one-step green synthesis.

Biofunctionalized silicon quantum dots were prepared through a one step strategy avoiding the use of chemical precursors. UV-Vis spectroscopy, Raman spectroscopy and HAADF-STEM prove oligonucleotide conjugation to the surface of silicon nanoparticle with an average size of 4 nm. The nanoparticle size results from the size-quenching effect during in situ conjugation. Photoemissive properties, conjugation efficiency and stability of these pure colloids were studied and demonstrate the bio-application potential, e.g. for nucleic acid vector delivery with semiconducting, biocompatible nanoparticles.

Electric-field-induced deformation dynamics of a single nematic disclination.

Disclinations in nematic liquid crystals usually adopt a straight shape in order to minimize their elastic energy. Once created in the course of a nonequilibrium process such as a temperature quench from the isotropic to the nematic phase, the topologically stable disclinations of half-integer strength either annihilate each other in pairs of opposite strength or form topologically unstable disclinations of integer strength. In this article, we demonstrate that the annihilation process can be inhibited and the defects can be deformed by an applied electric field. We study the disclination lines in the deep uniaxial nematic phase, located at the boundary between two different types of walls, the so-called pi wall (a planar soliton stabilized by the surface anchoring) and the Brochard-Léger (BL) wall stabilized by the applied electric field. By changing the electric voltage, one can control the energy of director deformations associated with the two walls and thus control the deformation and dynamics of the disclination line. At small voltages, the disclinations are straight lines connecting the opposite plates of the cell, located at the two ends of the pi walls. The pi walls tend to shrink. When the voltage increases above E(F), the Fréedericksz threshold, the BL walls appear and connect pairs of disclinations along a path complementary to the pi wall. At E>2 E(F), the BL walls store sufficient energy to prevent shrinking of the pi walls. Reconstruction of the three-dimensional director configuration using a fluorescent confocal polarizing microscopy demonstrates that the disclinations are strongly bent in the region between the pi and the BL walls. The distortions and the related dynamics are associated with the transformation of the BL wall into two surface disclination lines; we characterize it experimentally as a function of the applied electric field, the cell thickness, and the sample temperature. A simple model captures the essential details of the experimental data.