The hydrophobicity of nanoparticles (NPs) is a key property determining environmental fate, biological partitioning and toxicity. However, methods to characterize surface hydrophobicity are not ...uniformly applied to NPs and cannot quantify surface changes in complex environments. Existing methods designed to evaluate the hydrophobicity of bulk solids, chemicals, and proteins have significant limitations when applied to NPs. In this study, we modified and evaluated two methods to determine the hydrophobicity of NPs, hydrophobic interaction chromatography (HIC) and dye adsorption, and compared them to the standard octanol-water partitioning protocol for chemicals. Gold, copper oxide, silica, and amine-functionalized silica NPs were used to evaluate methods based on their applicability to NPs that agglomerate and have surface coatings. The octanol water partitioning and HIC methods both measured Au NPs as hydrophilic, but despite having a small size and stable suspension, NPs could not be fully recovered from the HIC column. For the dye adsorption method, hydrophobic (Rose Bengal) and hydrophilic (Nile Blue) dyes were adsorbed to the NP surface, and linear isotherm parameters were used as a metric for hydrophobicity. CuO was determined to be slightly hydrophilic, while SiO.sub.2 was hydrophilic and Ami-SiO.sub.2 was hydrophobic. The advantages and limitations of each method are discussed, and the dye adsorption method is recommended as the most suitable for application across broad classes of nanomaterials. The dye assay method was further used to measure changes in the surface hydrophobicity of TiO.sub.2 NPs after being suspended in natural water collected from the Alsea Rivers watershed in Oregon. TiO.sub.2 NPs adsorbed Rose Bengal when suspended in ultrapure water, but adsorbed Nile Blue after being incubated in natural water samples, demonstrating a shift from hydrophobic to hydrophilic properties on the outer surface. The dye adsorption method can be applied to characterize surface hydrophobicity of NPs and quantify environmental transformations, potentially improving environmental fate models.
Mitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDA-approved B cell lymphoma 2 (BCL-2) inhibitor venetoclax, but resistance to this agent is emerging. We show ...that venetoclax resistance in chronic lymphocytic leukemia is associated with complex clonal shifts. To identify determinants of resistance, we conducted parallel genome-scale screens of the BCL-2-driven OCI-Ly1 lymphoma cell line after venetoclax exposure along with integrated expression profiling and functional characterization of drug-resistant and engineered cell lines. We identified regulators of lymphoid transcription and cellular energy metabolism as drivers of venetoclax resistance in addition to the known involvement by BCL-2 family members, which were confirmed in patient samples. Our data support the implementation of combinatorial therapy with metabolic modulators to address venetoclax resistance.
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•B-lymphoid cancer cells can escape to venetoclax by overexpressing MCL-1•Modulation of AMPK/PKA axis and lymphoid transcription drive venetoclax resistance•Venetoclax resistance involves changes in cellular energy metabolism such as OXPHOS•Metabolic modulators can cooperate with venetoclax to overcome resistance
Guièze et al. show that resistance to the BCL-2 inhibitor venetoclax in chronic lymphocytic leukemia is associated with complex clonal shifts and identify, in addition to the known involvement by BCL-2 family members, regulators of lymphoid transcription and cellular energy metabolism as resistance drivers.
Copper based nanoparticles (NPs) are used extensively in industrial and commercial products as sensors, catalysts, surfactants, antimicrobials, and for other purposes. The high production volume and ...increasing use of copper-based NPs make their ecological risk a concern. Commonly used copper-based NPs are composed of metallic copper or copper oxide (Cu and CuO NPs); however, their environmental toxicity can vary dramatically depending on their physico-chemical properties, such as dissolution, aggregation behavior, and the generation of reactive oxygen species. Here, we investigated the NP dissolution, organismal uptake and aquatic toxicity of Cu and CuO NPs at 0, 0.1, 1, 5 or 10 mg Cu per L using a previously developed multi-species microcosm. This 5 day microcosm assay was comprised of
C. reinhardtti
,
E. coli
,
D. magna
, and
D. rerio
. We hypothesized that Cu and CuO NPs can elicit differential toxicity to the organisms due to alterations in particle dissolution and variations in organismal uptake. The actual concentrations of dissolved Cu released from the NPs were compared to ionic copper controls (CuCl
2
) at the same concentrations to determine the relative contribution of particulate and dissolved Cu on organism uptake and toxicity. We found that both NPs had higher uptake in
D. magna
and zebrafish than equivalent ionic exposures, suggesting that both Cu-based NPs are taken up by organisms. Cu NP exposures significantly inhibited algal growth rate,
D. magna
survival, and zebrafish hatching while exposure to equivalent concentrations of CuCl
2
(dissolved Cu fraction) and CuO NPs did not. This indicates that Cu NPs themselves likely elicited a particle-specific mechanism of toxicity to the test organisms, or a combination effect from ionic Cu and the Cu NPs. Overall, this work was the first study to utilize a small-scale rapid assay designed to evaluate the fate and ecotoxicological impacts of Cu and CuO NPs in a mixed aquatic community.
An efficient and rapid testing paradigm to evaluate the biological uptake, distribution, and ecological risks of Cu based NPs.
Surface functionalization can minimize nanoparticle agglomeration and expand their applications; however, these modifications can also alter particle stability, dissolution, bioavailability and ...toxicity. Here we investigated how silver nanoparticles (AgNPs) with different surface chemistries affect community health, and how increased trophic complexity affects the interactions between organisms and nanomaterials. We compared AgNP exposures in simple microcosms comprised of algae ( Chlamydomonas reinhardtii ) and bacteria ( Escherichia coli ) to increasingly complex microcosms containing predatory invertebrates ( Daphnia magna ) and developing vertebrates ( Danio rerio ). Each microcosm was exposed to one of three 70 nm AgNPs polyethylene glycol (PEG–AgNP), silica (Si–AgNP), or aminated silica-coated AgNP (Ami-Si–AgNP) at 0, 0.1, 1, and 5 mg L −1 to investigate the relative influence of surface charge, composition and dissolution on organismal uptake and toxicity. All three AgNPs released more dissolved Ag into solution when organisms were present than was measured in the same media without organisms. PEG–AgNPs had the highest overall toxicity in all scenarios, followed by Si–AgNPs, and lastly Ami-Si–AgNPs. Toxicity correlated with the amount of Ag measured in the exposure media and the amount taken up by the organisms. Our findings indicate that surface functionalization plays an important role in determining dissolution, uptake and toxicity of AgNPs. Increasing trophic complexity decreased organismal susceptibility under the same AgNP concentration exposures, likely due to the change in bioavailable Ag that each organism experienced. This implies that tests using individual species provide conservative estimates of environmental impacts, while exposure may be mitigated in more realistic multi-species scenarios like those found in nature.
•The chronic uptake and toxicity of CuO NPs were evaluated in D. magna.•CuO NPs can transfer through the food chain from algae to D. magna.•The uptake and toxicity of CuO NPs is dependent on the type ...of exposure.•Dietary exposure resulted in lower toxicity and accumulated Cu compared to direct exposure.•D. magna can regulate Cu through maternal transfer and molting after dietary exposure to CuO NPs.
Research examining the direct and indirect ecological effects of nanomaterials in aquatic ecosystems is important for developing a more realistic understanding of the environmental implications of nanotechnology. Copper oxide nanoparticles (CuO NPs) are being used extensively in many industries but are considered highly toxic to aquatic species residing in surface waters. Few studies have addressed whether CuO NPs can be transferred through the aquatic food chain, and if such indirect exposure to nanomaterials impacts their toxicity. We investigated the uptake and trophic transfer of CuO NPs from the algae Chlorella vulgaris to the crustacean Daphnia magna and assessed bio-partitioning and resulting toxicity. We hypothesized that CuO NPs can be associated with algal cells and be transported to predators through feeding, and that the chronic toxicity can be altered in comparison to direct CuO NP exposure. For the indirect feeding exposure, algae pre-incubated with CuO NPs (Cu-algae) were washed to remove loose NPs and fed to D. magna while Cu uptake and toxicity were evaluated. For the direct waterborne exposures, a parallel group of D. magna were exposed to equivalent concentrations of CuO NPs while being fed unexposed algae. Using hyperspectral imaging we observed strong surface associations between pre-incubated CuO NPs and algae used in the feeding exposure, and quantified the average Cu content (0.15mg Cu/L) with ICP-OES. Cu accumulated in daphnid bodies to a greater extent in direct exposures, whereas molted carapaces and neonate offspring had more copper following the indirect feeding exposure, implying that D. magna may regulate internal Cu differently depending on the method of CuO NP delivery. Significantly higher D. magna mortality was observed following direct exposure relative to feeding exposure, and neonate production from adult daphnids exposed indirectly to CuO NPs was significantly reduced. Thus, nanoparticle interaction with biota at one trophic level may alter the biological response at the next trophic level in a way that is dependent on the delivery scenario. This study highlights the importance of evaluating potential ecological impacts of nanomaterials in more relevant, complex exposure scenarios.
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.
The widespread use of silver nanoparticles (AgNPs) in various applications and industries has brought to light the need for understanding the complex relationship between the physicochemical ...properties (shape, size, charge, and surface chemistry) of AgNPs that affect their ability to enter cells and cause toxicity. To evaluate their toxicological outcomes, this study systematically analyzed a series of homogeneous hybrid lipid-coated AgNPs spanning sizes from 5 to 100 nm with diverse shapes (spheres, triangles, and cubes). The hybrid lipid membrane comprises hydrogenated phosphatidylcholine (HPC), sodium oleate (SOA), and hexanethiol (HT), which shield the AgNP surface from surface oxidation and toxic Ag+ ion release to minimize its contribution to toxicity. To reduce any significant effects by surface chemistry, the HPC, SOA, and HT membrane composition ratio was kept constant, and the AgNPs were assessed using embryonic zebrafish (Danio rerio). While a direct comparison cannot be drawn due to the lack of complementary sizes below 40 nm for triangular plates and cubes due to synthetic challenges, significant mortality was observed for spherical AgNPs (AgNSs) of 5, 20, 40, and 60 nm at 120 h postfertilization at concentrations ≥6 mg Ag/L. In contrast, the 10, 80, and 100 nm AgNSs, 40, 70, and 100 nm triangular plate AgNPs (AgNPLs), and 55, 75, and 100 nm cubic AgNPs (AgNCs) showed no significant mortality at 5 days postfertilization following exposure to AgNPs at concentrations up to 12 mg Ag/L. With constant surface chemistry on the AgNPs, size is the dominant factor driving toxicological responses, with smaller nanoparticles (5 to 60 nm) being the most toxic. Larger AgNSs, AgNCs, and AgNPLs from 75 to 100 nm do not show any evidence of toxicity. However, when closely examining sizes between 40 and 60 nm for AgNSs, AgNCs, and AgNPLs, there is evidence that discriminates shape as a driver of toxicity since sublethal responses generally were observed to follow a pattern, suggesting toxicity is most significant for AgNSs followed by AgNPLs and then AgNCs, which is the least toxic. Sum frequency generation vibrational spectroscopy showed that irrespective of size or shape, all hybrid lipid-coated AgNPs interact with membrane surfaces and “snorkel” between phases into the lipid monolayer with minimal energetic cost. These findings decisively demonstrate that not only smaller AgNPs but also the shape of the AgNPs influences their biological compatibility.
As plastic production continues to increase globally, plastic waste accumulates and degrades into smaller plastic particles. Through chemical and biological processes, nanoscale plastic particles ...(nanoplastics) are formed and are expected to exist in quantities of several orders of magnitude greater than those found for microplastics. Due to their small size and low mass, nanoplastics remain challenging to detect in the environment using most standard analytical methods. The goal of this research is to adapt existing tools to address the analytical challenges posed by the identification of nanoplastics. Given the unique and well-documented properties of anthropogenic plastics, we hypothesized that nanoplastics could be differentiated by polymer type using spatiotemporal deformation data collected through irradiation with scanning electron microscopy (SEM). We selected polyvinyl chloride (PVC), polyethylene terephthalate (PET), and high-density polyethylene (HDPE) to capture a range of thermodynamic properties and molecular structures encompassed by commercially available plastics. Pristine samples of each polymer type were chosen and individually milled to generate micro and nanoscale particles for SEM analysis. To test the hypothesis that polymers could be differentiated from other constituents in complex samples, the polymers were compared against proxy materials common in environmental media, i.e., algae, kaolinite clay, and nanocellulose. Samples for SEM analysis were prepared uncoated to enable observation of polymer deformation under set electron beam parameters. For each sample type, particles approximately 1 µm in diameter were chosen, and videos of particle deformation were recorded and studied. Blinded samples were also prepared with mixtures of the aforementioned materials to test the viability of this method for identifying near-nanoscale plastic particles in environmental media. Based on the evidence collected, deformation patterns between plastic particles and particles present in common environmental media show significant differences. A computer vision algorithm was also developed and tested against manual measurements to improve the usefulness and efficiency of this method further.
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