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Biomedical subjects

Vicki L Colvin

Publications and source records attributed to Vicki L Colvin.

At least 19 recordsLinked to original sources

Low-field magnetic separation of monodisperse Fe3O4 nanocrystals.

Magnetic separations at very low magnetic field gradients (<100 tesla per meter) can now be applied to diverse problems, such as point-of-use water purification and the simultaneous separation of complex mixtures. High-surface area and monodisperse magnetite (Fe3O4) nanocrystals (NCs) were shown to respond to low fields in a size-dependent fashion. The particles apparently do not act independently in the separation but rather reversibly aggregate through the resulting high-field gradients present at their surfaces. Using the high specific surface area of Fe3O4 NCs that were 12 nanometers in diameter, we reduced the mass of waste associated with arsenic removal from water by orders of magnitude. Additionally, the size dependence of magnetic separation permitted mixtures of 4- and 12-nanometer-sized Fe3O4 NCs to be separated by the application of different magnetic fields.

Journal Article↗

Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics.

Pulmonary toxicology studies in rats demonstrate that nanoparticles are more toxic than fine-sized particles of similar chemistry. This study, however, provides evidence to contradict this theory. The aims of the study were (1) to compare the toxicity of synthetic 50 nm nanoquartz I particles versus (mined) Min-U-Sil quartz ( approximately 500 nm); the toxicity of synthetic 12 nm nanoquartz II particles versus (mined) Min-U-Sil ( approximately 500 nm) versus (synthetic) fine-quartz particles (300 nm); and (2) to evaluate the surface activities among the samples as they relate to toxicity. Well-characterized samples were tested for surface activity and hemolytic potential. In addition, groups of rats were instilled with either doses of 1 or 5 mg/kg of carbonyl iron (CI) or various alpha-quartz particle types in phosphate-buffered saline solution and subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation, and histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postexposure. Exposures to the various alpha-quartz particles produced differential degrees of pulmonary inflammation and cytotoxicity, which were not always consistent with particle size but correlated with surface activity, particularly hemolytic potential. Lung tissue evaluations of three of the quartz samples demonstrated "typical" quartz-related effects--dose-dependent lung inflammatory macrophage accumulation responses concomitant with early development of pulmonary fibrosis. The various alpha-quartz-related effects were similar qualitatively but with different potencies. The range of particle-related toxicities and histopathological effects in descending order were nanoscale quartz II = Min-U-Sil quartz > fine quartz > nanoscale quartz I > CI particles. The results demonstrate that the pulmonary toxicities of alpha-quartz particles appear to correlate better with surface activity than particle size and surface area.

Animals↗

Water-soluble quantum dots for biomedical applications.

Semiconductor nanocrystals are 1-10nm inorganic particles with unique size-dependent optical and electrical properties due to quantum confinement (so they are also called quantum dots). Quantum dots are new types of fluorescent materials for biological labeling with high quantum efficiency, long-term photostability, narrow emission, and continuous absorption spectra. Here, we discuss the recent development in making water-soluble quantum dots and related cytotoxicity for biomedical applications.

Animals↗

Solvothermal synthesis and characterization of anatase TiO2 nanocrystals with ultrahigh surface area.

Phase-pure, ultrafine nanocrystalline anatase with high specific surface area (up to 250 m(2) g(-1)) was obtained upon injection of a titanium alkoxide precursor into ethanol with designed volume of water under mild solvothermal conditions (<200 degrees C, 2 h). Primary particle sizes were tuned by adjusting various reaction parameters, with the smallest grain sizes occurring at low temperatures (140-150 degrees C), low initial alkoxide concentrations, and intermediate hydrolysis ratios (r identical with[H2O]/[Ti(OR)4]=5-10). Additionally, variations in the reaction temperature result in changes in particle morphology and distribution, with high-temperature samples exhibiting bimodal distributions of small spherical and larger cubic particles that suggest grain growth via Ostwald ripening. A crystalline product with high thermal stability and specific surface area up to 5 times that of commercial nano-titania can be obtained at a relatively low temperature of 150 degrees C. The physical properties of the titania samples obtained in this study suggest they might be well suited for catalytic applications.

Adsorption↗

Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells.

Nanocrystalline titanium dioxide (nano-TiO(2)) is an important material used in commerce today. When designed appropriately it can generate reactive species (RS) quite efficiently, particularly under ultraviolet (UV) illumination; this feature is exploited in applications ranging from self-cleaning glass to low-cost solar cells. In this study, we characterize the toxicity of this important class of nanomaterials under ambient (e.g., no significant light illumination) conditions in cell culture. Only at relatively high concentrations (100 microg/ml) of nanoscale titania did we observe cytotoxicity and inflammation; these cellular responses exhibited classic dose-response behavior, and the effects increased with time of exposure. The extent to which nanoscale titania affected cellular behavior was not dependent on sample surface area in this study; smaller nanoparticlulate materials had effects comparable to larger nanoparticle materials. What did correlate strongly to cytotoxicity, however, was the phase composition of the nanoscale titania. Anatase TiO(2), for example, was 100 times more toxic than an equivalent sample of rutile TiO(2). The most cytotoxic nanoparticle samples were also the most effective at generating reactive oxygen species; ex vivo RS species generation under UV illumination correlated well with the observed biological response. These data suggest that nano-TiO(2) samples optimized for RS production in photocatalysis are also more likely to generate damaging RS species in cell culture. The result highlights the important role that ex vivo measures of RS production can play in developing screens for cytotoxicity.

Cell Line↗

Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: toxicity is not dependent upon particle size and surface area.

Pulmonary toxicology studies in rats demonstrate that nanoparticles administered to the lung are more toxic than larger, fine-sized particles of similar chemistry at identical mass concentrations. The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled pigment-grade TiO2 particles (rutile-type particle size = approximately 300 nm) versus nanoscale TiO2 rods (anatase = 200 nm x 35 nm) or nanoscale TiO2 dots (anatase = approximately 10 nm) compared with a positive control particle type, quartz. Groups of rats were instilled with doses of 1 or 5 mg/kg of the various particle types in phosphate-buffered saline (PBS). Subsequently, the lungs of PBS- and particle-exposed rats were assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation methods, and by the histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation exposure. Exposures to nanoscale TiO2 rods or nanoscale TiO2 dots produced transient inflammatory and cell injury effects at 24 h postexposure (pe) and were not different from the pulmonary effects of larger sized TiO2 particle exposures. In contrast, pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis. The results described herein provide the first example of nanoscale particle types which are not more cytotoxic or inflammogenic to the lung compared to larger sized particles of similar composition. Furthermore, these findings run counter to the postulation that surface area is a major factor associated with the pulmonary toxicity of nanoscale particle types.

Animals↗

Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro.

The cytotoxic response of cells in culture is dependant on the degree of functionalization of the single-walled carbon nanotube (SWNT). After characterizing a set of water-dispersible SWNTs, we performed in vitro cytotoxicity screens on cultured human dermal fibroblasts (HDF). The SWNT samples used in this exposure include SWNT-phenyl-SO(3)H and SWNT-phenyl-SO(3)Na (six samples with carbon/-phenyl-SO(3)X ratios of 18, 41, and 80), SWNT-phenyl-(COOH)(2) (one sample with carbon/-phenyl-(COOH)(2) ratio of 23), and underivatized SWNT stabilized in 1% Pluronic F108. We have found that as the degree of sidewall functionalization increases, the SWNT sample becomes less cytotoxic. Further, sidewall functionalized SWNT samples are substantially less cytotoxic than surfactant stabilized SWNTs. Even though cell death did not exceed 50% for cells dosed with sidewall functionalized SWNTs, optical and atomic force microscopies show direct contact between cellular membranes and water-dispersible SWNTs; i.e. the SWNTs in aqueous suspension precipitate out and selectively deposit on the membrane.

Cells, Cultured↗

Protease-activated quantum dot probes.

We have developed a novel nanoparticulate luminescent probe with inherent signal amplification upon interaction with a targeted proteolytic enzyme. This construct may be useful for imaging in cancer detection and diagnosis. In this system, quantum dots (QDs) are bound to gold nanoparticles (AuNPs) via a proteolytically degradable peptide sequence to non-radiatively suppress luminescence. A 71% reduction in luminescence was achieved with conjugation of AuNPs to QDs. Release of AuNPs by peptide cleavage restores radiative QD photoluminescence. Initial studies observed a 52% rise in luminescence over 47 h of exposure to 0.2 mg/mL collagenase. These probes can be customized for targeted degradation simply by changing the sequence of the peptide linker.

Coated Materials, Biocompatible↗

Synthesis and self-organization of soluble monodisperse palladium nanoclusters.

Control over size and size distribution of nanoparticles has been the subject of much interest during the past decade. In the present study, a simple strategy is described for obtaining monodisperse Pd nanoparticles with size less than 5 nm and size distribution around 10%. Without size-selective precipitation but with a simple reducing agent, hypophosphite, the synthesized Pd nanoparticles can form 2D well-ordered arrays on the TEM grids. When reducing agents were changed, no obvious size change of Pd nanoparticles was observed within experimental errors but the size distribution varied dramatically. In addition, stability, self-organized pattern, and solubility can be controlled by changing the capping agent. The present route is very simple and reproducible, and further study on the properties of the Pd nanoparticles is underway.

Journal Article↗

Characterization of nanocrystalline CdSe by size exclusion chromatography.

High-performance size exclusion chromatography (HPSEC) is a powerful tool for probing the size and size distribution of complex materials. Here we report its application to the analysis of cadmium selenide nanocrystals produced in organic solvents. If nanocrystal-column interactions are minimized, this method provides an accurate measure of nanocrystal hydrodynamic diameter directly in solution; such information is complementary to TEM in that it can measure the thickness of various capping agents. While the resolution of single-pass HPSEC is limited to 1 nm, we show here that recycling size exclusion chromatography can be applied to assess the fine details of a sample's distribution. Finally, semiconductor nanocrystals can be made a variety of shapes whose optical characteristics are difficult to distinguish. HPSEC can be applied to the general problem of shape separations which we demonstrate with a tetrapod material.

Cadmium Compounds↗

Virus crystals as nanocomposite scaffolds.

The generation of long-range three-dimensional nanoscopic patterns is a major goal in materials chemistry. Here we report a strategy for creating such systems using virus crystals as scaffolds which can be infiltrated with metal specifically palladium and platinum. The inorganic component effectively packs within the porous macromolecular crystal architecture, providing a route for patterning these materials on the nanometer length scale. To verify the quality of the metal infiltration, SEM-EDX was used to determine the homogeneous distribution of metal across the crystal, and TEM was used to confirm that the metal was confined within the porous structure of the crystal.

Colloids↗

Nano-C60 cytotoxicity is due to lipid peroxidation.

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C60, a fullerene aggregate that readily forms when pristine C60 is added to water. Nano-C60 was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses>or= 50 ppb (LC50=2-50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C60 colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C60 inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, L-ascorbic acid, the oxidative damage and resultant toxicity of nano-C60 was completely prevented.

Antioxidants↗

Analytical ultracentrifugation for characterizing nanocrystals and their bioconjugates.

Analytical ultracentrifugation (AU) provides a general way to probe the polydispersity of nanoparticles and the formation of bioconjugates in solution. Unconjugated gold nanocrystals show sedimentation coefficient distributions that are in agreement with size distributions as measured by TEM. AU is sensitive to the size/shape changes elicited by conjugation, in this case to lactose repressor (LacI). AU data reveal saturating protein concentrations for conjugates that correspond to the measured stoichiometry of the complex under these conditions.

Algorithms↗

Bacterial cell association and antimicrobial activity of a C60 water suspension.

Prior to the implementation of any new technology, possible environmental and health repercussions first must be researched. Fullerenes are to be produced soon on an industrial scale, with applications quickly following. To investigate the possible environmental impact of fullerenes, a C60-water suspension (nano-C60) was synthesized and then evaluated for cell-association and toxicity, using the bacteria Escherichia coli and Bacillus subtilis as indicator species. In a defined low-salts medium, nano-C60 associated with both the Gram-negative E. coli and the Gram-positive B. subtilis, albeit more strongly with the former. Nano-C60 also displayed antimicrobial properties against both E. coli and B. subtilis, with minimal inhibitory concentrations of 0.5 to 1 mg/ L and 1.5 to 3.0 mg/L, respectively. Media with higher salt contents result in the nano-C60 particles aggregating and falling out of suspension; thus, higher salt solutions reduced or eliminated the antimicrobial properties of nano-C60.

Anti-Bacterial Agents↗

Recycling size exclusion chromatography for the analysis and separation of nanocrystalline gold.

Recycling size exclusion chromatography (RSEC) provides a high-resolution technique for the analysis and separation of materials based on size. We show here the application of this method to gold nanocrystals stabilized by thiols. Alternate recycling is more effective at separating nanomaterials as compared to closed-loop recycling because of its improved efficiency and high resolution. With the use of this technique, we find the resolution ratio of nanocrystal separation increases with the square root of the cycle number, in good agreement with theory. The increased resolution of the size exclusion chromatograms permits the use of RSEC in the baseline separation of nanocrystals which differ by only 6 A in size. In addition to separations, RSEC is valuable as an analytical tool. For example, after recycling processes an initially broad and chromatographic feature from a gold nanocrystal solution resolves into three distinct peaks. Transmission electron microscopy of collected fractions reveals that these peaks correspond to distinct populations of gold nanoparticles with narrowly defined sizes.

Chromatography, Gel↗

The potential environmental impact of engineered nanomaterials.

With the increased presence of nanomaterials in commercial products, a growing public debate is emerging on whether the environmental and social costs of nanotechnology outweigh its many benefits. To date, few studies have investigated the toxicological and environmental effects of direct and indirect exposure to nanomaterials and no clear guidelines exist to quantify these effects.

Environment↗