Georgios A. Sotiriou

Antibacterial activity of nanosilver ions and particles.

The antibacterial activity of nanosilver against Gram negative Escherichia coli bacteria is investigated by immobilizing nanosilver on nanostructured silica particles and closely controlling Ag content and size. These Ag/SiO(2) nanoparticles were characterized by S/TEM, EDX spectroscopy, X-ray diffraction the exposed Ag surface area was measured qualitatively by O(2) chemisorption. Furthermore, the fraction of dissolved nanosilver was determined by measuring the released (leached) Ag(+) ion concentration in aqueous suspensions of such Ag/SiO(2) particles. The antibacterial effect of Ag(+) ions was distinguished from that of nanosilver particles by monitoring the growth of E. coli populations in the presence and absence of Ag/SiO(2) particles. The antibacterial activity of nanosilver was dominated by Ag(+) ions when fine Ag nanoparticles (less than about 10 nm in average diameter) were employed that release high concentrations of Ag(+) ions. In contrast, when relatively larger Ag nanoparticles were used, the concentration of the released Ag(+) ions was lower. Then the antibacterial activity of the released Ag(+) ions and nanosilver particles was comparable.

Toxicity of Silver Nanoparticles in Macrophages

Silver nanoparticles (nanosilver) are broadly used today in textiles, food packaging, household devices and bioapplications, prompting a better understanding of their toxicity and biological interactions. In particular, the cytotoxicity of nanosilver with respect to mammalian cells remains unclear, because such investigations can be biased by the nanosilver coatings and the lack of particle size control. Here, nanosilver of well-defined size (5.7 to 20.4 nm) supported on inert nanostructured silica is produced using flame aerosol technology. The cytotoxicity of the prepared nanosilver with respect to murine macrophages is assessed in vitro because these cells are among the first to confront nanosilver upon its intake by mammals. The silica support facilitates the dispersion and stabilization of the prepared nanosilver in biological suspensions, and no other coating or functionalization is applied that could interfere with the biointeractions of nanosilver. Detailed characterization of the particles by X-ray diffraction and electron microscopy reveals that the size of the nanosilver is well controlled. Smaller nanosilver particles release or leach larger fractions of their mass as Ag⁺ ions upon dispersion in water. This strongly influences the cytotoxicity of the nanosilver when incubated with murine macrophages. The size of the nanosilver dictates its mode of cytotoxicity (Ag⁺ ion-specific and/or particle-specific). The toxicity of small nanosilver (<10 nm) is mostly mediated by the released Ag⁺ ions. The influence of such ions on the toxicity of nanosilver decreases with increasing nanosilver size (>10 nm). Direct silver nanoparticle-macrophage interactions dominate the nanosilver toxicity at sizes larger than 10 nm.

Quantifying the Origin of Released Ag + Ions from Nanosilver

Nanosilver is most attractive for its bactericidal properties in modern textiles, food packaging, and biomedical applications. Concerns, however, about released Ag(+) ions during dispersion of nanosilver in liquids have limited its broad use. Here, nanosilver supported on nanostructured silica is made with closely controlled Ag size both by dry (flame aerosol) and by wet chemistry (impregnation) processes without any surface functionalization that could interfere with its ion release. It is characterized by electron microscopy, atomic absorption spectroscopy, and X-ray diffraction, and its Ag(+) ion release in deionized water is monitored electrochemically. The dispersion method of nanosilver in solutions affects its dissolution rate but not the final Ag(+) ion concentration. By systematically comparing nanosilver size distributions to their equilibrium Ag(+) ion concentrations, it is revealed that the latter correspond precisely to dissolution of one to two surface silver oxide monolayers, depending on particle diameter. When, however, the nanosilver is selectively conditioned by either washing or H(2) reduction, the oxide layers are removed, drastically minimizing Ag(+) ion leaching and its antibacterial activity against E. coli . That way the bactericidal activity of nanosilver is confined to contact with its surface rather than to rampant ions. This leads to silver nanoparticles with antibacterial properties that are essential for medical tools and hospital applications.

An Integrated Microrobotic Platform for On‐Demand, Targeted Therapeutic Interventions

The presented microrobotic platform combines together the advantages of self-folding NIR light sensitive polymer bilayers, magnetic alginate microbeads, and a 3D manipulation system, to propose a solution for targeted, on-demand drug and cell delivery. First feasibility studies are presented together with the potential of the full design.

Optically Stable Biocompatible Flame-Made SiO2-Coated Y2O3:Tb3+ Nanophosphors for Cell Imaging

Nanophosphors are light-emitting materials with stable optical properties that represent promising tools for bioimaging. The synthesis of nanophosphors, and thus the control of their surface properties, is, however, challenging. Here, flame aerosol technology is exploited to generate Tb-activated Y(2)O(3) nanophosphors (∼25 nm) encapsulated in situ by a nanothin amorphous inert SiO(2) film. The nanocrystalline core exhibits a bright green luminescence following the Tb(3+) ion transitions, while the hermetic SiO(2)-coating prevents any unspecific interference with cellular activities. The SiO(2)-coated nanophosphors display minimal photobleaching upon imaging and can be easily functionalized through surface absorption of biological molecules. Therefore, they can be used as bionanoprobes for cell detection and for long-term monitoring of cellular activities. As an example, we report on the interaction between epidermal growth factor (EGF)-functionalized nanophosphors and mouse melanoma cells. The cellular uptake of the nanophosphors is visualized with confocal microscopy, and the specific activation of EGF receptors is revealed with biochemical techniques. Altogether, our results establish SiO(2)-coated Tb-activated Y(2)O(3) nanophosphors as superior imaging tools for biological applications.

A novel platform for pulmonary and cardiovascular toxicological characterization of inhaled engineered nanomaterials

Abstract A novel method is presented which is suitable for assessing in vivo the link between the physicochemical properties of engineered nanomaterials (ENM) and their biological outcomes. The ability of the technique to generate a variety of industry-relevant, property-controlled ENM exposure atmospheres for inhalation studies was systematically investigated. The primary particle size for Fe2O3, SiO2, Ag and Ag/SiO2 was controlled from 4 to 25 nm, while the corresponding agglomerate mobility diameter of the aerosol was also controlled and varied from 40 to 120 nm. The suitability of the technique to characterize the pulmonary and cardiovascular effects of inhaled ENMs in intact animal models is also demonstrated using in vivo chemiluminescence (IVCL). The IVCL technique is a highly sensitive method for identifying cardiopulmonary responses to inhaled ENMs under relatively small doses and acute exposures. It is shown that moderate and acute exposures to inhaled nanostructured Fe2O3 can cause both pulmonary and cardiovascular effects.

Antioxidant and antiradical SiO2 nanoparticles covalently functionalized with gallic acid.

Gallic acid (GA) and its derivatives are natural polyphenolic substances widely used as antioxidants in nutrients, medicine and polymers. Here, nanoantioxidant materials are engineered by covalently grafting GA on SiO(2) nanoparticles (NPs). A proof-of-concept is provided herein, using four types of well-characterized SiO(2) NPs of specific surface area (SSA) 96-352 m(2)/g. All such hybrid SiO(2)-GA NPs had the same surface density of GA molecules (~1 GA per nm(2)). The radical-scavenging capacity (RSC) of the SiO(2)-GA NPs was quantified in comparison with pure GA based on the 2,2-diphenyl-1-picrylhydrazyl (DPPH(•)) radical method, using electron paramagnetic resonance (EPR) and UV-vis spectroscopy. The scavenging of DPPH radicals by these nanoantioxidant SiO(2)-GA NPs showed mixed-phase kinetics: An initial fast-phase (t(1/2) <1 min) corresponding to a H-Atom Transfer (HAT) mechanism, followed by a slow-phase attributed to secondary radical-radical reactions. The slow-reactions resulted in radical-induced NP agglomeration, that was more prominent for high-SSA NPs. After their interaction with DPPH radicals, the nanoantioxidant particles can be reused by simple washing with no impairment of their RSC.

Engineering safer-by-design silica-coated ZnO nanorods with reduced DNA damage potential

Zinc oxide (ZnO) nanoparticles absorb UV light efficiently while remaining transparent in the visible light spectrum rendering them attractive in cosmetics and polymer films. Their broad use, however, raises concerns regarding potential environmental health risks and it has been shown that ZnO nanoparticles can induce significant DNA damage and cytotoxicity. Even though research on ZnO nanoparticle synthesis has made great progress, efforts on developing safer ZnO nanoparticles that can maintain their inherent optoelectronic properties while exhibiting minimal toxicity are limited. Here, a safer-by-design concept was pursued by hermetically encapsulating ZnO nanorods in a biologically inert, nanothin amorphous SiO2 coating during their gas-phase synthesis. It is demonstrated that the SiO2 nanothin layer hermetically encapsulates the core ZnO nanorods without altering their optoelectronic properties. Furthermore, the effect of SiO2 on the toxicological profile of the core ZnO nanorods was assessed using the Nano-Cometchip assay by monitoring DNA damage at a cellular level using human lymphoblastoid cells (TK6). Results indicate significantly lower DNA damage (>3 times) for the SiO2-coated ZnO nanorods compared to uncoated ones. Such an industry-relevant, scalable, safer-by-design formulation of nanostructured materials can liberate their employment in nano-enabled products and minimize risks to the environment and human health.

Consumer exposures to laser printer-emitted engineered nanoparticles: A case study of life-cycle implications from nano-enabled products

Abstract It is well established that printers emit nanoparticles during their operation. To-date, however, the physicochemical and toxicological characterization of “real world” printer-emitted nanoparticles (PEPs) remains incomplete, hampering proper risk assessment efforts. Here, we investigate our earlier hypothesis that engineered nanomaterials (ENMs) are used in toners and ENMs are released during printing (consumer use). Furthermore, we conduct a detailed physicochemical and morphological characterization of PEPs in support of ongoing toxicological assessment. A comprehensive suite of state of the art analytical methods and tools was employed for the physicochemical and morphological characterization of 11 toners widely utilized in printers from major printer manufacturers and their PEPs. We confirmed that a number of ENMs incorporated into toner formulations (e.g. silica, alumina, titania, iron oxide, zinc oxide, copper oxide, cerium oxide, carbon black among others) and released into the air during printing. All evaluated toners contained large amounts of organic carbon (OC, 42–89%), metals/metal oxides (1–33%), and some elemental carbon (EC, 0.33–12%). The PEPs possess a composition similar to that of toner and contained 50–90% OC, 0.001–0.5% EC and 1–3% metals. While the chemistry of the PEPs generally reflected that of their toners, considerable differences are documented indicative of potential transformations taking place during consumer use (printing). We conclude that: (i) Routine incorporation of ENMs in toners classifies them as nano-enabled products (NEPs); (ii) These ENMs become airborne during printing; (iii) The chemistry of PEPs is complex and it reflects that of the toner and paper. This work highlights the importance of understanding life-cycle (LC) nano-EHS implications of NEPs and assessing real world exposures and associated toxicological properties rather than focusing on “raw” materials used in the synthesis of an NEP.

In Vitro Oxygen Sensing Using Intraocular Microrobots

We present a luminescence oxygen sensor integrated with a wireless intraocular microrobot for minimally-invasive diagnosis. This microrobot can be accurately controlled in the intraocular cavity by applying magnetic fields. The microrobot consists of a magnetic body susceptible to magnetic fields and a sensor coating. This coating embodies Pt(II) octaethylporphine (PtOEP) dyes as the luminescence material and polystyrene as a supporting matrix, and it can be wirelessly excited and read out by optical means. The sensor works based on quenching of luminescence in the presence of oxygen. The excitation and emission spectrum, response time, and oxygen sensitivity of the sensor were characterized using a spectrometer. A custom device was designed and built to use this sensor for intraocular measurements with the microrobot. Due to the intrinsic nature of luminescence lifetimes, a frequency-domain lifetime measurement approach was used. An alternative sensor design with increased performance was demonstrated by using poly(styrene-co-maleic anhydride) (PS-MA) and PtOEP nanospheres.