Reducing the cytotoxicity of inhalable engineered nanoparticles via in situ passivation with biocompatible materials.

The cytotoxicity of model welding nanoparticles was modulated through in situ passivation with soluble biocompatible materials. A passivation process consisting of a spark discharge particle generator coupled to a collison atomizer as a co-flow or counter-flow configuration was used to incorporate the model nanoparticles with chitosan. The tested model welding nanoparticles are inhaled and that A549 cells are a human lung epithelial cell line. Measurements of in vitro cytotoxicity in A549 cells revealed that the passivated nanoparticles had a lower cytotoxicity (>65% in average cell viability, counter-flow) than the untreated model nanoparticles. Moreover, the co-flow incorporation between the nanoparticles and chitosan induced passivation of the nanoparticles, and the average cell viability increased by >80% compared to the model welding nanoparticles. As a more convenient way (additional chitosan generation and incorporation devices may not be required), other passivation strategies through a modification of the welding rod with chitosan adhesive and graphite paste did also enhance average cell viability (>58%). The approach outlined in this work is potentially generalizable as a new platform, using only biocompatible materials in situ, to treat nanoparticles before they are inhaled.

Photoionization of nanosized aerosol gold agglomerates and their deposition to form nanoscale islands on substrates.

Positively charged gold nanoparticles can be produced in the aerosol state by ultraviolet irradiation of aerosols at wavelengths above the gold ionization energy. Spark-discharge-generated aerosol gold nanoparticles were mobility-classified, neutralized, and then exposed to ultraviolet irradiation at 185 nm. The charge states were determined using a tandem differential mobility analyzer system, and the results revealed that there was no significant dependence of charging probability upon mobility diameter between 4 and 60 nm (1.55 ± 0.26 in positive elementary charge), probably because of the agglomerated nature of the particles. The ionized particles could be deposited to form nanoscale island patterns on a substrate without the use of templates.

Photoassisted one-step aerosol fabrication of zwitterionic chitosan nanoparticles.

Zwitterionic chitosan nanoparticles (ZCNPs) were conveniently obtained by a one-step aerosol method, and their potential for the production of biocompatible materials was investigated. A low-molecular-weight chitosan was conjugated with succinic anhydride to produce zwitterionic chitosan (ZC). Collison-atomized ZC droplets were simultaneously UV-irradiated and dried in a tube furnace in a one-step aerosol process to produce particles. The observed cytotoxicities of ZCNPs (85 ± 3.9% cell viability) were similar to unmodified chitosan nanoparticles (CNPs, 88 ± 6.6%) and UV-irradiated ZCNPs (83 ± 3.3%). The aerosol process described in this work allowed facile production and modification of CNPs, which could then be employed for biomedical purposes.

Aerosol-based fabrication of modified chitosans and their application for gene transfection.

Modified chitosan nanoparticles were conveniently obtained by a one-step aerosol method, and their potential for gene transfection was investigated. Droplets containing modified chitosans were formed by collison atomization, dried to form solid particles, and collected and studied for potential use as nanocarriers. Modified chitosans consisted of a chitosan backbone and an additional component [covalently attached cholesterol; or blends with poly(l-lysine) (PLL), polyethyleneimine (PEI), or poly(ethylene glycol) (PEG)]. Agarose gel retardation assays confirmed that modified chitosans could associate with plasmid DNA. Even though the average cell viability of cholesterol-chitosan (Ch-Cs) showed a slightly higher cytotoxicity (∼90% viability) than that for unmodified chitosan (Cs, ∼95%), transfection (>7.5 × 10(5) in relative light units (RLU) mg(-1)) was more effective than it was for Cs (∼7.6 × 10(4) RLU mg(-1)). The blending of PEI with Cs (i.e., a Cs/PEI) to produce transfection complexes enhanced the transfection efficiency (∼1.3 × 10(6) RLU mg(-1)) more than did the addition of PLL (i.e., a Cs/PLL, ∼9.3 × 10(5) RLU mg(-1)); however, it also resulted in higher cytotoxicity (∼86% viability for Cs/PEI vs ∼94% for Cs/PLL). The average cell viability (∼92%) and transfection efficiency (∼1.9 × 10(6) RLU mg(-1)) were complemented further by addition of PEG in Cs/PEI complexes (i.e., a Cs/PEI-PEG). This work concludes that gene transfection of Cs can be significantly enhanced by adding cationic polymers during aerosol fabrication without wet chemical modification processes of Cs.

Monodisperse poly(lactide-co-glycolic acid)-based nanocarriers for gene transfection.

This contribution describes a simple, aerosol-based method for fabricating monodisperse particles containing mixtures of poly(lactide-co-glycolic acid) [PLGA], protamine sulfate (Prot), and poly(l-lysine) [PLL] as nanocarriers for gene transfection. Aqueous solutions of PLGA, Prot, and PLL were collison-atomized, and the resulting aerosolized droplets were dried "on the fly" to form solid particles, which then were electrostatically size-classified into 50, 100, and 200 nm mobility diameter samples. Measurements of cell viability and transfection reveal that the fabricated nanocarriers have a lower cytotoxicity (>85% in cell viability) and a higher transfection efficiency [>8.7 × 10(5) in relative light units (RLU) mg(-1) ] than does 25 kDa polyethyleneimine (≈50% and 6.8 × 10(5) RLU mg(-1) ).

Silver deposition on a polymer substrate catalyzed by singly charged monodisperse copper nanoparticles.

Aerosol deposition of singly charged monodisperse copper nanoparticles was used to catalytically activate a polymer substrate for electroless silver deposition. An ambient spark discharge was used to produce aerosol copper nanoparticles, and the particles were electrostatically classified at an equivalent mobility diameter of 10 nm, using a nanodifferential mobility analyzer. Deposition of the copper particles onto the surface of the substrate was enhanced by thermophoresis. The copper-deposited substrate was then immersed in a Ag(I) solution, resulting in the electroless deposition of silver (∼17 µm line width) on the previously deposited copper (∼12 µm line width, using a shadow mask with a 100 µm in width patterned stripe). The arithmetic mean roughness and electrical resistivity of the silver pattern were 44.7 nm and 7.9 µΩ cm, respectively, which showed an enhancement compared to those from the nonclassified copper particles (roughness = 162.2 nm, resistivity = 13.3 µΩ cm), because of a more-uniform copper deposition.

Aerosol-based fabrication of biocompatible organic-inorganic nanocomposites.

Several novel nanoparticle composites were conveniently obtained by appropriately reacting freshly produced aerosol metal nanoparticles with soluble organic components. A serial reactor consisting of a spark particle generator coupled to a collison atomizer was used to fabricate the new materials, which included nanomagnetosols (comprising iron nanoparticles, the drug ketoprofen, and a Eudragit shell), hybrid nanogels (comprising iron nanoparticles and an N-isopropylacrylamide, NIPAM, gel), and nanoinorganics (gold immobilized silica). A fourth hybrid material, consisting of iron-gold nanoparticles and NIPAM) was obtained via an aerosol into liquid configuration, in which aerosol iron-gold particles were collected into a NIPAM/ethanol solution and then formed into nanogels with NIPAM under ultrasonic treatment. The strategy outlined in this work is potentially generalizable as a new platform for creating biocompatible nanocomposites, using only clinically approved starting materials in a single pass and under low-temperature conditions.

SiO2 coating of silver nanoparticles by photoinduced chemical vapor deposition.

Gas-phase silver nanoparticles were coated with silicon dioxide (SiO2) by photoinduced chemical vapor deposition (photo-CVD). Silver nanoparticles, produced by inert gas condensation, and a SiO2 precursor, tetraethylorthosilicate (TEOS), were exposed to vacuum ultraviolet (VUV) radiation at atmospheric pressure and varying temperatures. The VUV photons dissociate the TEOS precursor, initiating a chemical reaction that forms SiO2 coatings on the particle surfaces. Coating thicknesses were measured for a variety of operation parameters using tandem differential mobility analysis and transmission electron microscopy. The chemical composition of the particle coatings was analyzed using energy dispersive x-ray spectrometry and Fourier transform infrared spectroscopy. The highest purity films were produced at 300-400 degrees C with low flow rates of additional oxygen. The photo-CVD coating technique was shown to effectively coat nanoparticles and limit core particle agglomeration at concentrations up to 10(7) particles cm(-3).

Thermally induced hydrosilylation at deuterium-terminated silicon nanoparticles: an investigation of the radical chain propagation mechanism.

Isotopic labeling techniques were employed to study alkene addition to hydrogen- and deuterium-terminated silicon nanoparticles. Deuterium-terminated silicon nanoparticle synthesis is described, as is the characterization of fresh deuterium-terminated particles by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and in situ Fourier transform infrared spectroscopy (FTIR). Particles were refluxed in pure 1-dodecene and subsequently characterized by FTIR and nuclear magnetic resonance (NMR) spectroscopy. (1)H NMR results showed features consistent with dodecyl-terminated nanoparticles. Infrared absorption spectra of refluxed particles showed strong evidence of new C-D bond formation, which is consistent with a radical chain mechanism for alkene addition by hydrosilylation.

Thermal oxidation of 6 nm aerosolized silicon nanoparticles: size and surface chemistry changes.

The earliest stages of thermal oxidation of 6 nm diameter silicon nanoparticles by molecular oxygen are examined using a tandem differential mobility analysis (TDMA) apparatus, Fourier-transform infrared (FTIR) spectroscopy, time-of-flight secondary ion mass spectroscopy (ToF-SIMS), and X-ray photoelectron spectroscopy (XPS). Particles are synthesized in and then extracted from a nonthermal RF plasma operating at approximately 20 Torr into the atmospheric pressure TDMA apparatus. The TDMA apparatus was used to measure oxidation-induced size changes over a broad range of temperature settings and N2-O2 carrier gas composition. Surface chemistry changes are evaluated in situ with an FTIR spectrometer and a hybrid flow-through cell, and ex situ with ToF-SIMS and XPS. Particle size measurements show that, at temperatures less than approximately 500 degrees C, particles shrink regardless of the carrier gas oxygen concentration, while FTIR and ToF-SIMS spectra demonstrate a loss of hydrogen from the particles and minimal oxide formation. At higher temperatures, FTIR and XPS spectra indicate that an oxide forms which tends toward, but does not fully reach, stoichiometric SiO2 with increasing temperature. Between 500 and 800 degrees C, size measurements show a small increase in particle diameter with increasing carrier gas oxygen content and temperature. Above 800 degrees C, particle growth rapidly reaches a plateau while FTIR and XPS spectra change little. ToF-SIMS signals associated with O-Si species also show an increase in intensity at 800 degrees C.

Surface chemistry of aerosolized silicon nanoparticles: evolution and desorption of hydrogen from 6-nm diameter particles.

The surface chemistry of pristine, 6-nm silicon nanoparticles has been investigated. The particles were produced in an RF plasma and studied using a tandem differential mobility analysis apparatus, Fourier transform infrared spectroscopy (FTIR), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and transmission electron microscopy. Particles were extracted from the plasma, which operates at approximately 20 Torr, into an atmospheric pressure aerosol flow tube, and then through a variable-temperature furnace that could be adjusted between room temperature and 1200 degrees C. DMA measurements show that freshly generated silicon particles shrink with heating, with particle diameters decreasing by approximately 0.25 nm between 350 and 400 degrees C. FTIR results indicate that freshly generated particles are primarily covered with SiH2 groups and smaller amounts of SiH and SiH3. Spectra recorded as a function of heating temperature indicate that the amount of surface hydrogen, as measured by the intensity of modes associated with SiH, SiH2, and SiH3, decreases with heating. ToF-SIMS measurements also suggest that hydrogen desorbs from the particles surfaces over the same temperature range that the particles shrink.

Self-assembly of organic monolayers on aerosolized silicon nanoparticles.

A new method is described for surface functionalization of silicon nanocrystals. Organic monolayers were self-assembled via gas-phase adsorption of amines, alkenes, alkynes, and aldehydes onto the surfaces of aerosolized crystalline silicon nanoparticles of 12.2 nm diameter in an atmospheric pressure tube reactor. Assembly took place within 4 s at temperatures between 200 and 500 degrees C. The extent of adsorption was measured by using tandem differential mobility analysis (T-DMA), an on-line diagnostic method for measuring changes in particle size. Functionalized particles were further characterized by high-resolution transmission electron microscopy and diffuse reflectance Fourier transform infrared spectroscopy. The apparatus described in this work can be used for continuous mass production of functionalized silicon nanoparticles. Moreover, the overall strategy of using T-DMA for monitoring monolayer uptake could be generally applied to study surface processing of other aerosolized nanoparticle systems.

Heterogeneous chemistry of carbon aerosols.

Atmospheric carbon particles originate from natural sources and from human activity. The processes that lead to their formation are varied and include fossil fuel combustion, biomass burning, and mechanical stress and wear of carbonaceous materials. In this review, we examine recent work on the structure and composition of carbon aerosol particles, and we describe how they react with the atmospherically abundant gases ozone, oxygen, sulfur dioxide, nitric acid, and nitrogen oxides. The study of carbon particles in the laboratory has shown that chemical reactivity depends strongly on the type of carbon used and on experimental conditions such as temperature and humidity. The variability in the results demonstrates the difficulty in extrapolating laboratory results to atmospheric conditions and in explaining the role of carbon particles in processes such as global warming and environmental chemical cycling.

Surface chemistry of aerosolized nanoparticles:thermal oxidation of silicon.

The kinetics of reaction between silicon nanoparticles and molecular oxygen were studied by tandem differential mobility analysis. Aerosolized silicon nanoparticles were extracted from a low-pressure silane plasma into an atmospheric pressure aerosol flow tube reactor. Particles were initially passed through a differential mobility analyzer that was set to transmit only those particles having mobility diameters of approximately 10 nm. The monodisperse particle streams were mixed with oxygen/nitrogen mixtures of different oxygen volume fractions and allowed to react over a broad temperature range (600-1100 degrees C) for approximately one second. Particles were size-classified after reaction with a second differential mobility analyzer. The particle mobility diameters increased upon oxidation by up to 1.3 nm, depending on the oxygen volume fraction and the reaction temperature. Oxidation is described by a kinetic model that considers both oxygen diffusion and surface reaction, with diffusion becoming important after formation of a 0.5 nm thick oxide monolayer.

Surface chemistry of nanometer-sized aerosol particles: reactions of molecular oxygen with 30 nm soot particles as a function of oxygen partial pressure.

The kinetics of the reaction between soot nanoparticles and molecular oxygen were studied by tandem differential mobility analysis (TDMA). The particles were extracted from the tip of an ethene diffusion flame. Reactions were studied at atmospheric pressure in mixtures of nitrogen and oxygen. The studies involved particles of an initial mobility diameter of 30 nm over broad ranges of temperature (500-1100 degrees C) and oxygen volume fraction (0-1). Measurements as a function of oxygen partial pressure establish that the oxidation kinetics are not first-order in oxygen volume fraction (F(O2)). Rather, the oxidation rate increases rapidly and linearly with F(O2) between 0 and 0.05 and then more slowly but still linearly between 0.05 and 1. Temperature dependent measurements are consistent with a reaction pathway involving two kinetically distinguishable oxidation sites which interconvert thermally and through oxidation. Results and conclusions are compared to those of earlier studies on the oxidation of soot.

Kinetics of diesel nanoparticle oxidation.

The technique of high-temperature oxidation tandem differential mobility analysis has been applied to the study of diesel nanoparticle oxidation. The oxidation rates in air of diesel nanoparticles sampled directly from the exhaust stream of a medium-duty diesel engine were measured over the temperature range of 800-1140 degrees C using online aerosol techniques. Three particle sizes (40, 90, and 130 nm mobility diameter) generated under engine load conditions of 10, 50, and 75% were investigated. The results show significant differences in the behavior of the 10% load particles as compared to the 50 and 75% load particles. The 10% load particles show greater size decrease at temperatures below 500 degrees C and significant size decrease at temperatures between 500 and 1000 degrees C in a non-oxidative environment, indicating release of adsorbed volatile material or thermally induced rearrangement of the agglomerate structure. Activation energies determined are 114, 109, and 108 kJ mol(-1) for the 10, 50, and 75% load particles, respectively. These activation energies are lower than for flame soot (Higgins et al. J. Phys. Chem. A 2002, 106, 96), but the preexponential factors are lower by 3 orders of magnitude, and the overall oxidation rates are slower by up to a factor of 4 over the temperature range studied. Possible reasons for the differences are discussed in the text.