Impacts of Differentially Shaped Silver Nanoparticles with Increasingly Complex Hydrophobic Thiol Surface Coatings in Small-Scale Laboratory Microcosms.

We investigated the impacts of spherical and triangular-plate-shaped lipid-coated silver nanoparticles (AgNPs) designed to prevent surface oxidation and silver ion (Ag+) dissolution in a small-scale microcosm to examine the role of shape and surface functionalization on biological interactions. Exposures were conducted in microcosms consisting of algae, bacteria, crustaceans, and fish embryos. Each microcosm was exposed to one of five surface chemistries within each shape profile (at 0, 0.1, or 0.5 mg Ag/L) to investigate the role of shape and surface composition on organismal uptake and toxicity. The hybrid lipid-coated AgNPs did not result in any significant release of Ag+ and had the most significant toxicity to D. magna, the most sensitive species, although the bacterial population growth rate was reduced in all exposures. Despite AgNPs resulting in increasing algal growth over the experiment, we found no correlation between algal growth and the survival of D. magna, suggesting that the impacts of the AgNPs on bacterial survival influenced algal growth rates. No significant impacts on zebrafish embryos were noted in any exposure. Our results demonstrate that the size, shape, and surface chemistry of AgNPs can be engineered to achieve specific goals while mitigating nanoparticle risks.

Silver Nanoparticles Stable to Oxidation and Silver Ion Release Show Size-Dependent Toxicity In Vivo.

Silver nanoparticles (AgNPs) are widely used in commerce, however, the effect of their physicochemical properties on toxicity remains debatable because of the confounding presence of Ag+ ions. Thus, we designed a series of AgNPs that are stable to surface oxidation and Ag+ ion release. AgNPs were coated with a hybrid lipid membrane comprised of L-phosphatidylcholine (PC), sodium oleate (SOA), and a stoichiometric amount of hexanethiol (HT) to produce oxidant-resistant AgNPs, Ag-SOA-PC-HT. The stability of 7-month aged, 20-100 nm Ag-SOA-PC-HT NPs were assessed using UV-Vis, dynamic light scattering (DLS), and inductively coupled plasma mass spectrometry (ICP-MS), while the toxicity of the nanomaterials was assessed using a well-established, 5-day embryonic zebrafish assay at concentrations ranging from 0-12 mg/L. There was no change in the size of the AgNPs from freshly made samples or 7-month aged samples and minimal Ag+ ion release (<0.2%) in fishwater (FW) up to seven days. Toxicity studies revealed AgNP size- and concentration-dependent effects. Increased mortality and sublethal morphological abnormalities were observed at higher concentrations with smaller nanoparticle sizes. This study, for the first time, determined the effect of AgNP size on toxicity in the absence of Ag+ ions as a confounding variable.

Size-Dependent Interactions of Lipid-Coated Gold Nanoparticles: Developing a Better Mechanistic Understanding Through Model Cell Membranes and in vivo Toxicity.

INTRODUCTION: Humans are intentionally exposed to gold nanoparticles (AuNPs) where they are used in variety of biomedical applications as imaging and drug delivery agents as well as diagnostic and therapeutic agents currently in clinic and in a variety of upcoming clinical trials. Consequently, it is critical that we gain a better understanding of how physiochemical properties such as size, shape, and surface chemistry drive cellular uptake and AuNP toxicity in vivo. Understanding and being able to manipulate these physiochemical properties will allow for the production of safer and more efficacious use of AuNPs in biomedical applications. METHODS AND MATERIALS: Here, AuNPs of three sizes, 5 nm, 10 nm, and 20 nm, were coated with a lipid bilayer composed of sodium oleate, hydrogenated phosphatidylcholine, and hexanethiol. To understand how the physical features of AuNPs influence uptake through cellular membranes, sum frequency generation (SFG) was utilized to assess the interactions of the AuNPs with a biomimetic lipid monolayer composed of a deuterated phospholipid 1.2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (dDPPC). RESULTS AND DISCUSSION: SFG measurements showed that 5 nm and 10 nm AuNPs are able to phase into the lipid monolayer with very little energetic cost, whereas, the 20 nm AuNPs warped the membrane conforming it to the curvature of hybrid lipid-coated AuNPs. Toxicity of the AuNPs were assessed in vivo to determine how AuNP curvature and uptake influence cell health. In contrast, in vivo toxicity tested in embryonic zebrafish showed rapid toxicity of the 5 nm AuNPs, with significant 24 hpf mortality occurring at concentrations ≥20 mg/L, whereas the 10 nm and 20 nm AuNPs showed no significant mortality throughout the five-day experiment. CONCLUSION: By combining information from membrane models using SFG spectroscopy with in vivo toxicity studies, a better mechanistic understanding of how nanoparticles (NPs) interact with membranes is developed to understand how the physiochemical features of AuNPs drive nanoparticle-membrane interactions, cellular uptake, and toxicity.

A hybrid lipid membrane coating "shape-locks" silver nanoparticles to prevent surface oxidation and silver ion dissolution.

The controlled synthesis of stable silver nanoparticles (AgNPs), that do not undergo surface oxidation and Ag+ ion dissolution, continues to be a major challenge. Here the synthesis of robust hybrid lipid-coated AgNPs, comprised of l-α-phosphatidylcholine (PC) membranes anchored by a stoichiometric amount of long-chained hydrophobic thiols and sodium oleate (SOA) as hydrophobic binding partners, that do not undergo surface oxidation and Ag+ ion dissolution, is described. UV-Visible (UV-Vis) spectroscopy, transmission electron microscopy (TEM), and inductively coupled plasma mass spectrometry (ICP-MS) demonstrate that in the presence of strong oxidants, such as potassium cyanide (KCN), the hybrid lipid-coated AgNPs are stable and do not undergo surface oxidation even in the presence of membrane destabilizing surfactants. UV-Vis studies show that the stability of hybrid lipid-coated AgNPs of various sizes and shapes is dependent on the length of the thiol hydrocarbon chain and can be ranked in the order of increasing stability as follows: propanethiol (PT) < hexanethiol (HT) ≤ decanethiol (DT). UV-Vis and ICP-MS studies show that the hybrid lipid-coated AgNPs do not change in size or shape confirming that the AgNPs do not undergo surface oxidation and Ag+ ion dissolution when placed in the presence of strong oxidants, chlorides, thiols, and low pH. Long-term stability studies, over 21 days, show that the hybrid lipid-coated AgNPs do not release Ag+ ions and are more stable. Overall, these studies demonstrate hybrid membrane encapsulation of nanomaterials is a viable method for stabilizing AgNPs in a "shape-locked" form that is unable to undergo surface oxidation, Ag+ ion release, aging, or shape conversion. More importantly, this design strategy is a simple approach to the synthesis and stabilization of AgNPs for a variety of biomedical and commercial applications where Ag+ ion release and toxicity is a concern. With robust and shielded AgNPs, investigators can now evaluate and correlate how the physical features of AgNPs influence toxicity without the confounding factor of Ag+ ions present in samples. This design strategy also provides an opportunity where the membrane composition can be tuned to control the release rate of Ag+ ions for optimizing antimicrobial activity.