Gold nanoparticles (AuNPs) exhibit unique size-dependent physiochemical properties that make them attractive for a wide range of applications. However, the large-scale availability of precision AuNPs has been minimal. Not only must the required nanoparticles be of precise size and morphology, but they must also be of exceedingly narrow size distribution to yield accurate and reliable performance. The present study aims to synthesize precision AuNPs and to assess the advantages and limitations of the Turkevich method-one of the common chemical synthesis technique. Colloidal AuNPs from 15 nm to 50 nm in diameter were synthesized using the Turkevich method. The effect of the molar ratio of the reagent mixture (trisodium citrate to gold chloride), the scaled-up batch size, the initial gold chloride concentration, and the reaction temperature was studied. The morphology, optical property, surface chemistry, and chemical composition of AuNPs were thoroughly characterized. It was determined that the as-synthesized AuNPs between 15 nm and 30 nm exhibit well-defined size and shape, and narrow size distribution (PDI < 0.20). However, the AuNPs became more polydispersed and less spherical in shape as the particle size increased.

Due to the unique physicochemical properties exhibited by materials with nanoscale dimensions, there is currently a continuous increase in the number of engineered nanomaterials (ENMs) used in consumer goods. However, several reports associate ENM exposure to negative health outcomes such as cardiovascular diseases. Therefore, understanding the pathological consequences of ENM exposure represents an important challenge, requiring model systems that can provide mechanistic insights across different levels of ENM-based toxicity. To achieve this, we developed a mussel-inspired 3D microphysiological system (MPS) to measure cardiac contractility in the presence of ENMs. While multiple cardiac MPS have been reported as alternatives to in vivo testing, most systems only partially recapitulate the native extracellular matrix (ECM) structure. Here, we show how adhesive and aligned polydopamine (PDA)/polycaprolactone (PCL) nanofiber can be used to emulate the 3D native ECM environment of the myocardium. Such nanofiber scaffolds can support the formation of anisotropic and contractile muscular tissues. By integrating these fibers in a cardiac MPS, we assessed the effects of TiO and Ag nanoparticles on the contractile function of cardiac tissues. We found that these ENMs decrease the contractile function of cardiac tissues through structural damage to tissue architecture. Furthermore, the MPS with embedded sensors herein presents a way to non-invasively monitor the effects of ENM on cardiac tissue contractility at different time points. These results demonstrate the utility of our MPS as an analytical platform for understanding the functional impacts of ENMs while providing a biomimetic microenvironment to in vitro cardiac tissue samples. Graphical Abstract Heart-on-a-chip integrated with mussel-inspired fiber scaffolds for a high-throughput toxicological assessment of engineered nanomaterials.

BackgroundParticle size is thought to be a critical factor affecting the bioavailability of nanoparticles following oral exposure. Nearly all studies of nanoparticle bioavailability focus on characterization of the primary particle size of the material as supplied or as dosed, and not on agglomeration behavior within the gastrointestinal tract, which is presumably most relevant for absorption.MethodsIn the study reported here, snapshots of agglomeration behavior of gold nanospheres were evaluated in vivo throughout the gastrointestinal tract using transmission electron microscopy. Agglomeration state within the gastrointestinal tract was then used to help explain differences in gastrointestinal particle absorption, as indicated by tissue levels of gold detected using inductively coupled plasma mass spectrometry. Mice were dosed (10 mg/kg) with either 23 nm PEG-coated or uncoated gold nanospheres.ResultsTransmission electron microscopy demonstrates that PEG-coated gold nanoparticles can be observed as primary, un-agglomerated particles throughout the gastrointestinal tract and feces of dosed animals. In contrast, uncoated gold nanoparticles were observed to form agglomerates of several hundred nanometers in all tissues and feces. Inductively coupled plasma mass spectrometry shows significantly higher levels of gold in tissues from animals dosed with PEG-coated versus uncoated 23 nm gold nanoparticles. Retention of particles after a single oral gavage was also very high, with all tissues of animals dosed with PEG-coated particles having detectable levels of gold at 30 days following exposure.ConclusionsQualitative observation of these particles in vivo shows that dispersed PEG-coated particles are able to reach the absorptive tissues of the intestine while agglomerated uncoated particles are sequestered in the lumen of these tissues. However, the large differences observed for in vivo agglomeration behavior were not reflected in oral absorption, as indicated by gold tissue levels. Additional factors, such as surface chemistry, may have played a more important role than in vivo particle size and should be investigated further.

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Metallic nanoparticles can be produced in a variety of shapes, sizes, and surface chemistries, making them promising potential tools for drug delivery. Most studies to date have evaluated uptake of metallic nanoparticles from the GI tract with methods that are at best semiquantitative. This study used the classical method of comparing blood concentration area under the curve (AUC) following intravenous and oral doses to determine the oral bioavailability of 1, 2 and 5 kDa PEG-coated 5 nm gold nanoparticles (AuNPs). Male rats were given a single intravenous dose (0.8 mg/kg) or oral (gavage) dose (8 mg/kg) of a PEG-coated AuNP, and the concentration of gold was measured in blood over time and in tissues (liver, spleen and kidney) at sacrifice. Blood concentrations following oral administration were inversely related to PEG size, and the AUC in blood was significantly greater for the 1 kDa PEGcoated AuNPs than particles coated with 2 or 5 kDa PEG. However, bioavailabilities of all of the particles were very low (50.1%). Concentrations in liver, spleen and kidney were similar after the intravenous doses, but kidney showed the highest concentrations after an oral dose. In addition to providing information on the bioavailability of AuNPs coated with PEG in the 1-5 kDa range, this study demonstrates the utility of applying the blood AUC approach to assess the quantitative oral bioavailability of metallic nanoparticles.

Gold nanoparticles are one of the most extensively investigated metallic nanoparticles for several applications. It is less toxic than other metallic nanolattices. The exceptional electrical and thermal conductivity of gold make it possible to be administered as non-invasive radiofrequency irradiation therapy that produces sufficient heat to kill tumor cells. Nanoparticles are generally administered intravenously instead of orally due to negligible oral absorption and cellular uptake. This study evaluated the oral bioavailability of gold nanoparticles coated with chitosan (C-AuNPs), a natural mucoadhesive polymer. We employed traditional method of evaluating bioavailability that involve estimation of maximum concentrations and area under the curve of 3 nm chitosan coated gold nanoparticles (C-AuNPs) in the rat plasma following intravenous and oral administrations (0.8 mg and 8 mg/kg body weight respectively). The oral bioavailability of C-AuNPs was found to be 2.46% (approximately 25 folds higher than polyethylene glycol (PEG) coated gold nanoparticles, reported earlier). These findings suggest that chitosan coating could be better than PEG coating for the enhancement of oral bioavailability of nanoparticles.

In freshwater fish, aluminum is a well-recognized gill toxicant, although responses are influenced by pH. Aluminum nanomaterials are being used in diverse applications that are likely to lead to environmental release and exposure. However, it is unclear if the effects of nanoparticulate aluminum are similar to those of other forms of aluminum or require special consideration. To examine the acute toxicological effects of exposure to aluminum nanoparticle (Al-NP)s, adult female zebrafish were exposed to either Al-NPs or aluminum chloride for up to 48 hours in moderately hard fresh water. Al-NPs introduced into test water rapidly aggregated and up to 80% sedimented from the water column during exposures. No mortality was caused by concentrations of Al-NP up to 12.5 mg/L. After exposure, tissue concentrations of aluminum, effects on gill morphology, Na+, K+ -ATPase (NKA) activity, and global gene expression patterns were examined. Exposure to both aluminum chloride and nanoparticulate aluminum resulted in a concentration dependent decrease in sodium potassium ATPase activity, although Al-NP exposure did not alter gill morphology as measured by filament widths. Decreased ATPase activity coincided with decreases in filamental NKA staining and mucous cell counts. Analysis of gill transcriptional responses demonstrated that exposure to 5 mg/L Al-NP only resulted in significant changes in expression of two genes, whereas aluminum chloride exposure significantly affected the expression of 105 genes. Taken together, these results indicate that nanoparticulate aluminum has little acute toxicity for zebrafish in moderately hard freshwater.

The scientific community, regulatory agencies, environmentalists, and most industry representatives all agree that more effort is required to ensure the responsible and safe development of new nanotechnologies. Characterizing nanomaterials is a key aspect in this effort. There is no universally agreed upon minimum set of characteristics although certain common properties are included in most recommendations. Therefore, characterization becomes more like a puzzle put together with various measurements rather than a single straightforward analytical measurement. In this chapter, we emphasize and illustrate the important elements of nanoparticle characterization with a systematic approach to physicochemical characterization. We start with an overview describing the properties that are most significant to toxicological testing along with suggested methods for characterizing an as-received nanomaterial and then specifically address the measurement of size, surface properties, and imaging.