Recent Advances in Laser-Ablative Synthesis of Bare Au and Si Nanoparticles and Assessment of Their Prospects for Tissue Engineering Applications.

Driven by surface cleanness and unique physical, optical and chemical properties, bare (ligand-free) laser-synthesized nanoparticles (NPs) are now in the focus of interest as promising materials for the development of advanced biomedical platforms related to biosensing, bioimaging and therapeutic drug delivery. We recently achieved significant progress in the synthesis of bare gold (Au) and silicon (Si) NPs and their testing in biomedical tasks, including cancer imaging and therapy, biofuel cells, etc. We also showed that these nanomaterials can be excellent candidates for tissue engineering applications. This review is aimed at the description of our recent progress in laser synthesis of bare Si and Au NPs and their testing as functional modules (additives) in innovative scaffold platforms intended for tissue engineering tasks.

Importance of surface topography on pulsed laser-induced damage threshold of Sapphire crystals.

We measure the laser-induced damage threshold (LIDT) fluence under single shot at the surface of Sapphire samples prepared following the standards of two methods yielding to different surface finish and used in optical and laser industry. We use AFM microscopy to measure the roughness parameter Ra and power spectral density (PSD) of the sample surface. We show that the quality of surface topography resulting from surface preparation affects the damage threshold of Sapphire crystals exposed to femtosecond, picosecond, and nanosecond laser conditions at visible and near-infrared wavelengths. We observe a higher resistance to laser damage or macroscopic modification when the surface finish presents a smooth and regular topography. We indeed measure a 1.4 to 2 times increase of the LIDT fluence in femtosecond and picosecond regimes and up to 5 times with nanosecond pulses. Using simple damage model and PSD data, we correlate the LIDT reduction of Sapphire samples of lower quality of surface finish with the high-frequency tail component of their PSD distribution corresponding to striations of the width of a fraction of the laser wavelength. This study emphasizes the importance of detailed assessment of surface topography for laser damage evaluation and understanding and for indicating directions of improvement.

Ultrapure laser-synthesized Si-based nanomaterials for biomedical applications: in vivo assessment of safety and biodistribution.

Si/SiOx nanoparticles (NPs) produced by laser ablation in deionized water or aqueous biocompatible solutions present a novel extremely promising object for biomedical applications, but the interaction of these NPs with biological systems has not yet been systematically examined. Here, we present the first comprehensive study of biodistribution, biodegradability and toxicity of laser-synthesized Si-SiOx nanoparticles using a small animal model. Despite a relatively high dose of Si-NPs (20 mg/kg) administered intravenously in mice, all controlled parameters (serum, enzymatic, histological etc.) were found to be within safe limits 3 h, 24 h, 48 h and 7 days after the administration. We also determined that the nanoparticles are rapidly sequestered by the liver and spleen, then further biodegraded and directly eliminated in urine without any toxicity effects. Finally, we found that intracellular accumulation of Si-NPs does not induce any oxidative stress damage. Our results evidence a huge potential in using these safe and biodegradable NPs in biomedical applications, in particular as vectors, contrast agents and sensitizers in cancer therapy and diagnostics (theranostics).

Ultrapure laser-synthesized Si nanoparticles with variable oxidation states for biomedical applications.

We employ a method of femtosecond laser fragmentation of preliminarily prepared water-dispersed microcolloids to fabricate aqueous solutions of ultrapure bare Si-based nanoparticles (Si-NPs) and assess their potential for biomedical applications. The nanoparticles appear spherical in shape, with low size dispersion and a controllable mean size, from a few nm to several tens of nm, while a negative surface charge (-35 mV ± 0.10 according to z-potential data) provides good electrostatic stabilization of colloidal Si-NP solutions. Structural analysis shows that the Si-NPs are composed of Si nanocrystals with inclusions of silicon oxide species, covered by a SiOx (1 < x < 2) shell, while the total oxide content depends on whether the fragmentation is performed in normal oxygen-saturated water (oxygen-rich conditions) or in water deoxygenated by pumping with noble gases (Ag or He) before and during the experiment (oxygen-free conditions). Our dissolution tests show the excellent water-solubility of all the NPs, while more oxidized NPs demonstrate much faster dissolution kinetics, which is explained by oxidation-induced defects in the core of the Si-NPs. Finally, by examining the interaction of the NPs with human cells after 72 h of incubation at different concentrations, we report the absence of any adverse effects of the NPs up to high concentrations (50 µg mL-1) and a good internalization of NPs via a classical endocytosis mechanism. Possessing far superior purity compared to their chemically synthesized counterparts and enabling a variety of imaging and therapeutic functionalities, the laser-synthesized Si-NPs are promising for safe and efficient applications in nanomedicine.

Size-controllable synthesis of bare gold nanoparticles by femtosecond laser fragmentation in water.

We report a size-controllable synthesis of stable aqueous solutions of ultrapure low-size-dispersed Au nanoparticles by methods of femtosecond laser fragmentation from preliminary formed colloids. Such approach makes possible the tuning of mean nanoparticle size between a few nm and several tens of nm under the size dispersion lower than 70% by varying the fluence of pumping radiation during the fragmentation procedure. The efficient size control is explained by 3D geometry of laser fragmentation by femtosecond laser-induced white light super-continuum and plasma-related phenomena. Despite the absence of any protective ligands, the nanoparticle solutions demonstrate exceptional stability due to electric repulsion effect associated with strong negative charging of formed nanoparticles. Stable aqueous solutions of bare gold nanoparticles present a unique object with a variety of potential applications in catalysis, surface-enhanced Raman spectroscopy, photovoltaics, biosensing and biomedicine.

Gold nanoparticles prepared by laser ablation in aqueous biocompatible solutions: assessment of safety and biological identity for nanomedicine applications.

Due to excellent biocompatibility, chemical stability, and promising optical properties, gold nanoparticles (Au-NPs) are the focus of research and applications in nanomedicine. Au-NPs prepared by laser ablation in aqueous biocompatible solutions present an essentially novel object that is unique in avoiding any residual toxic contaminant. This paper is conceived as the next step in development of laser-ablated Au-NPs for future in vivo applications. The aim of the study was to assess the safety, uptake, and biological behavior of laser-synthesized Au-NPs prepared in water or polymer solutions in human cell lines. Our results showed that laser ablation allows the obtaining of stable and monodisperse Au-NPs in water, polyethylene glycol, and dextran solutions. The three types of Au-NPs were internalized in human cell lines, as shown by transmission electron microscopy. Biocompatibility and safety of Au-NPs were demonstrated by analyzing cell survival and cell morphology. Furthermore, incubation of the three Au-NPs in serum-containing culture medium modified their physicochemical characteristics, such as the size and the charge. The composition of the protein corona adsorbed on Au-NPs was investigated by mass spectrometry. Regarding composition of complement C3 proteins and apolipoproteins, Au-NPs prepared in dextran solution appeared as a promising drug carrier. Altogether, our results revealed the safety of laser-ablated Au-NPs in human cell lines and support their use for theranostic applications.

Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy.

Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50 °C under relatively low nanoparticle concentrations (<1 mg/mL) and RF radiation intensities (1-5 W/cm(2)). For both types of nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

Influence of pyrene grafting on PMMA nanosecond laser ablation at 248 nm.

In this work, we investigate the effects of KrF nanosecond laser ablation on poly(methyl methacrylate) (PMMA) in combination with pyrene. Three materials containing PMMA were studied: (1) one doped with pure pyrene, (2) one doped with methyl 3-(1-pyrenyl)propanoate (so called alkylpyrene derivative thereafter), and (3) one grafted with pyrene. This last new material was developed by covalently bonding pyrene molecules to PMMA side-chains. A comparative study was undertaken to determine and compare the respective properties of the PMMA dye containing pyrene during nanosecond laser ablation at 248 nm. Cavities were etched for each material with up to 20 pulses for fluences between 0.03 and 1.7 J/cm(2) in samples containing 1, 2, and 4 mol % chromophore. The threshold fluences and the effective absorption coefficients were obtained. It was observed that effective absorption coefficients increased and threshold fluences decreased with the chromophore percentages in each kind of sample. Ablation parameters were not significantly modified when the dopant was changed from pyrene to the alkylpyrene derivative. On the other hand, when pyrene molecules were grafted on the polymer, the threshold fluences decreased, whereas the effective absorption coefficients became similar at fluences above 0.6 J/cm(2).

Ultra-pure, water-dispersed Au nanoparticles produced by femtosecond laser ablation and fragmentation.

Aqueous solutions of ultra-pure gold nanoparticles have been prepared by methods of femtosecond laser ablation from a solid target and fragmentation from already formed colloids. Despite the absence of protecting ligands, the solutions could be (1) fairly stable and poly size-dispersed; or (2) very stable and monodispersed, for the two fabrication modalities, respectively. Fluorescence quenching behavior and its intricacies were revealed by fluorescence lifetime imaging microscopy in rhodamine 6G water solution. We show that surface-enhanced Raman scattering of rhodamine 6G on gold nanoparticles can be detected with high fidelity down to micromolar concentrations using the nanoparticles. Application potential of pure gold nanoparticles with polydispersed and nearly monodispersed size distributions are discussed.

Femtosecond laser fragmentation from water-dispersed microcolloids: toward fast controllable growth of ultrapure Si-based nanomaterials for biological applications.

An ultrashort laser-assisted method for fast production of concentrated aqueous solutions of ultrapure Si-based colloidal nanoparticles is reported. The method profits from the 3D geometry of femtosecond laser ablation of water-dispersed microscale colloids, prepared preliminarily by the mechanical milling of a Si wafer, in order to avoid strong concentration gradients in the ablated material and provide similar conditions of nanocluster growth within a relatively large laser caustics volume. We demonstrate the possibility for the fast synthesis of non-aggregated, low-size-dispersed, crystalline Si-based nanoparticles, whose size and surface oxidation can be controlled by changing the initial microcolloid concentration and the amount of dissolved oxygen in the water. Due to their much superior purity compared to the chemically synthesized counterparts and their photoluminescence response, the nanoparticles present the possibility for biological in vivo applications such as drug vectoring, imaging, and therapeutics.

Laser-generated plasma plume expansion: combined continuous-microscopic modeling.

The physical phenomena involved in the interaction of a laser-generated plasma plume with a background gas are studied numerically. A three-dimensional combined model is developed to describe the plasma plume formation and its expansion in vacuum or into a background gas. The proposed approach takes advantages of both continuous and microscopic descriptions. The simulation technique is suitable for the simulation of high-rate laser ablation for a wide range of background pressure. The model takes into account the mass diffusion and the energy exchange between the ablated and background species, as well as the collective motion of the ablated species and the background-gas particles. The developed approach is used to investigate the influence of the background gas on the expansion dynamics of the plume obtained during the laser ablation of aluminum. At moderate pressures, both plume and gas compressions are weak and the process is mainly governed by the diffusive mixing. At higher pressures, the interaction is determined by the plume-gas pressure interplay, the plume front is strongly compressed, and its center exhibits oscillations. In this case, the snowplough effect takes place, leading to the formation of a compressed gas layer in front of the plume. The background pressure needed for the beginning of the snowplough effect is determined from the plume and gas density profiles obtained at various pressures. Simulation results are compared with experimentally measured density distributions. It is shown that the calculations suggest localized formation of molecules during reactive laser ablation.