Antibacterial efficacy, mode of action, and safety of a novel nano-antibiotic against antibiotic-resistant Escherichia coli strains.

Globally rising antibiotic-resistant (AR) and multi-drug resistant (MDR) bacterial infections are of public health concern due to treatment failure with current antibiotics. Enterobacteria, particularly Escherichia coli, cause infections of surgical wound, bloodstream, and urinary tract, including pneumonia and sepsis. Herein, we tested in vitro antibacterial efficacy, mode of action (MoA), and safety of novel amino-functionalized silver nanoparticles (NH2-AgNP) against the AR bacteria. Two AR E. coli strains (i.e., ampicillin- and kanamycin-resistant E. coli), including a susceptible strain of E. coli DH5α, were tested for susceptibility to NH2-AgNP using Kirby-Bauer disk diffusion and standard growth assays. Dynamic light scattering (DLS) was used to determine cell debris and relative conductance was used as a measure of cell leakage, and results were confirmed with transmission electron microscopy (TEM). Multiple oxidative stress assays were used for in vitro safety evaluation of NH2-AgNP in human lung epithelial cells. Results showed that ampicillin and kanamycin did not inhibit growth in either AR bacterial strain with doses up to 160 µg/mL tested. NH2-AgNP exhibited broad-spectrum bactericidal activity, inhibiting the growth of all three bacterial strains at doses ≥1 µg/mL. DLS and TEM revealed cell debris formation and cell leakage upon NH2-AgNP treatment, suggesting two possible MoAs: electrostatic interactions followed by cell wall damage. Safety evaluation revealed NH2-AgNP as noncytotoxic and antioxidative to human lung epithelial cells. Taken together, these results suggest that NH2-AgNP may serve as an effective and safer bactericidal therapy against AR bacterial infections compared to common antibiotics.

Asthma May Not be a Potential Risk Factor for Severe COVID-19 Illness: A Scoping Review.

The coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), but whether the asthmatic patients are at increased risk for severe COVID-19 illness than non-asthmatic patients has remained unclear. This scoping review aimed to assess the available evidence to determine if asthmatic patients are at a higher risk for severe COVID-19 illness. Searching several electronic databases and adhering to the PRISMA guidelines, we conducted a scoping review of 70 articles and using defined inclusion-exclusion criteria, 21 articles were analyzed in-depth and included in this scoping review. The findings of this scoping review point to a lack of relationship between asthma and severe COVID-19 illness. While a limited number of studies (n = 4) identified asthma as a risk factor, most studies (n = 17) found no independent association between asthma and severe COVID-19 illness. We, thus, conclude that asthma may not be a potential risk factor for severe COVID-19 illness. Owing to limited evidence, we recommend large-scale prospective cohort studies with standardized methodologies to decipher potential role of asthma in COVID-19 severity. Further, understanding the impact of specific asthma medications, genetic factors, and other comorbidities on COVID-19 outcomes may help inform clinical practice guidelines for effective patient health management.

MicroRNAs: Small but Key Players in Viral Infections and Immune Responses to Viral Pathogens.

Since the discovery of microRNAs (miRNAs) in C. elegans in 1993, the field of miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at the post-transcriptional phase to regulate protein expression. miRNAs are known to regulate viral infection and the ensuing host immune response. Evolving research suggests miRNAs are assets in the discovery and investigation of therapeutics and diagnostics. In this review, we succinctly summarize the latest findings in (i) mechanisms underpinning miRNA regulation of viral infection, (ii) miRNA regulation of host immune response to viral pathogens, (iii) miRNA-based diagnostics and therapeutics targeting viral pathogens and challenges, and (iv) miRNA patents and the market landscape. Our findings show the differential expression of miRNA may serve as a prognostic biomarker for viral infections in regard to predicting the severity or adverse health effects associated with viral diseases. While there is huge market potential for miRNA technology, the novel approach of using miRNA mimics to enhance antiviral activity or antagonists to inhibit pro-viral miRNAs has been an ongoing research endeavor. Significant hurdles remain in terms of miRNA delivery, stability, efficacy, safety/tolerability, and specificity. Addressing these challenges may pave a path for harnessing the full potential of miRNAs in modern medicine.

Extended-spectrum ß-lactamases producing Enterobacteriaceae (ESBL-PE) prevalence in Nepal: A systematic review and meta-analysis.

An alarming increase in the occurrence of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) has threatened the treatment and management of bacterial infections. This systematic review and meta-analysis aimed to provide a quantitative estimate of the prevalence of ESBL among the members of the Enterobacteriaceae family by analyzing the community-based and clinical studies published between 2011 and 2021 from Nepal and determine if ESBL-PE correlates with multidrug resistance (MDR). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed for systematic review and meta-analysis and the articles' quality was assessed using the Newcastle-Ottawa scale. Of the 2529 articles screened, 65 articles were systematically reviewed, data extracted, and included in in-depth meta-analysis. The overall pooled prevalence of ESBL-producers in Enterobacteriaceae was 29 % (95 % CI: 26-32 %) with high heterogeneity (I2 = 96 %, p < 0.001). Escherichia coli was the predominant ESBL-producing member of the Enterobacteriaceae family, followed by Citrobacter spp. and Klebsiella spp. The prevalence of ESBL-PE increased from 18.7 % in 2011 to 29.5 % in 2021. A strong positive correlation (r = 0.98) was observed between ESBL production and MDR in Enterobacteriaceae. ESBL-PE isolates showed high resistance to ampicillin, cephalosporins, and amoxicillin-clavulanic acid, and blaCTX-M type was the most reported gene variant among ESBL-PE. In conclusion, this study demonstrated an increased prevalence of ESBL-PE in Nepal over the last decade, and such isolates showed a high level of MDR against the ß-lactams and non-ß-lactam antibiotics. Tackling the rising antibiotic resistance (AR) and MDR in ESBL-PE would require concerted efforts from all stakeholders to institute effective infection control programs in the community and clinical settings.

Isolation of Lactococcus garvieae NEP21 from raw cow (Bos indicus) milk in Nepal.

Lactococcus garvieae is an emerging zoonotic pathogen impacting both humans and animals. Infection of this bacterium is known to cause mastitis in cattle, and endocarditis, osteomyelitis, liver abscess, and gastrointestinal problems are reported in immunocompromised and elderly people that regularly consume or handle raw meat, milk, dairy products, and seafood. This study aimed at investigating and detecting lactic acid bacteria in raw cow (Bos indicus) milk samples from a smallholder farm in Nepal. Based on the plate culture, biochemical tests, and molecular sequencing of 16 s ribosomal RNA coding nuclear DNA region followed by phenotypic and genotypic analyses, L. garvieae NEP21 was detected and identified for the first time in Nepal in raw cow milk samples. This finding suggests the prevalence of L. garvieae NEP21 in raw cow milk and recommends further research and surveillance for understanding the extent of its presence in Nepal and globally for informed management of its infection in cattle and humans.

Cellular miR-6741-5p as a Prognostic Biomarker Predicting Length of Hospital Stay among COVID-19 Patients.

Wide variability exists with host response to SARS-CoV-2 infection among individuals. Circulatory micro RNAs (miRNAs) are being recognized as promising biomarkers for complex traits, including viral pathogenesis. We hypothesized that circulatory miRNAs at 48 h post hospitalization may predict the length of stay (LOS) and prognosis of COVID-19 patients. Plasma miRNA levels were compared between three groups: (i) healthy volunteers (C); (ii) COVID-19 patients treated with remdesivir (an antiviral) plus dexamethasone (a glucocorticoid) (with or without baricitinib, a Janus kinase inhibitor) on the day of hospitalization (I); and COVID-19 patients at 48 h post treatment (T). Results showed that circulatory miR-6741-5p expression levels were significantly different between groups C and I (p < 0.0000001); I and T (p < 0.0000001); and C and T (p = 0.001). Our ANOVA model estimated that all patients with less than 12.42 Log2 CPM had a short LOS, or a good prognosis, whereas all patients with over 12.42 Log2 CPM had a long LOS, or a poor prognosis. In sum, we show that circulatory miR-6741-5p may serve as a prognostic biomarker effectively predicting mortality risk and LOS of hospitalized COVID-19 patients.

Prevalence of metallo-ß-lactamases as a correlate of multidrug resistance among clinical Pseudomonas aeruginosa isolates in Nepal.

Pseudomonas aeruginosa is an opportunistic human pathogen that has developed antibiotic resistance (AR) and causes a range of illnesses, including respiratory pneumonia, gastrointestinal infections, keratitis, otitis media and bacteremia in patients with compromised immune system. The production of metallo-ß-lactamases (MBLs) is one of the major mechanisms of AR in this bacterium with ensuing infections difficult to treat. The main goal of this study was to provide a quantitative estimate of MBLs producing clinical P. aeruginosa isolates among the Nepalese patients and determine if MBL correlates with multi-drug resistance (MDR). Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline was followed for meta-analysis of relevant literature using PubMed, Research4Life, and Google Scholar. The prevalence of MBLs in P. aeruginosa from clinical samples was determined using R 4.1.2 for data pooled from studies published until 2021. The meta-analysis of a total of 19 studies selected (of 6038 studies for which titles and abstracts were reviewed) revealed the prevalence of MBLs producing P. aeruginosa (MBL-PA) was 14 % (95 % CI: 0.10-0.19) while MDR isolates among P. aeruginosa was 42 % (95 % CI: 0.30-0.55) in Nepal. Combined Disc Test was predominantly used phenotypic method for confirming MBLs phenotypes among the studies. Sputum was the most common specimen from which MBL-PA was recovered. A significant positive correlation was observed between MDR and MBL production in P. aeruginosa. We conclude that MBL producing strains are widespread among the clinical isolates of P. aeruginosa in Nepal and responsible for emerging MDR strains. It is paramount that antibiotics prescription against the bacterium should be monitored closely and alternative therapeutic modalities against MBL-PA explored.

Understanding COVID-19 Situation in Nepal and Implications for SARS-CoV-2 Transmission and Management.

Background: The pandemic of Coronavirus Disease 2019 (COVID-19), one of the most infectious diseases in the modern history, is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and has had a profound health and economic toll, globally. This paper identifies the overall health status associated with COVID-19 pandemic in all 7 provinces of Nepal, a developing country in South Asia, analyzing data from January 2020 to February 2022. It focuses on the SARS-CoV-2 prevalence, transmission through wastewater and other routes, diagnostics, treatment options, and alternative medicines, thereby offering key perspectives for its management. Materials and Methods: Studies regarding coronavirus spanning the 2017 to 2022 period were searched on the web, Nepalese database, and Web of Science. Refined criteria included SARS-CoV-2 in wastewater of Nepal or worldwide. Demographic data (sex, age-group, and geographic location) were also obtained from websites and relevant reports of the Ministry of Health and Population (MOHP) of Nepal, ranging from January 2020 to February 2022. Moreover, trends concerning lockdown, business, and border activities in Nepal between February 2020 and October 2020 were evaluated. The viral dissemination pathways, diagnosis, and available treatment options, including the Ayurvedic medicine, were also examined. Results: Aerosols generated during the hospital, industrial, recreational, and household activities were found to contribute to the propagation of SARS-CoV-2 into environmental wastewater, thereby putting the surrounding communities at risk of infection. When lockdown ended and businesses opened in October 2020, the number of active cases of COVID-19 increased exponentially. Bagmati Province had the highest number of cases (53.84%), while the remaining 6 provinces tallied 46.16%. Kathmandu district had the highest number of COVID-19 cases (138, 319 cases), while Manang district had the smallest number of infections (81 cases). The male population was found to be predominantly infected (58.7%). The most affected age groups were the 31 to 40 years old males (25.92%) and the 21 to 30 years old females (26.85%). Conclusion: The pandemic impacted the public health and economic growth in our study duration. SARS-CoV-2 was prevalent in the wastewater of Nepal. The Terai districts and the megacities were mostly affected by SARS-CoV-2 infections. Working-age groups and males were identified as the highest risk groups. More investigations on the therapeutic and alternative cures are recommended. These findings may guide the researchers and professionals with handling the COVID-19 challenges in developing countries such as Nepal and better prepare for future pandemics.

Five nanometer size highly positive silver nanoparticles are bactericidal targeting cell wall and adherent fimbriae expression.

To tackle growing antibiotic resistance (AR) and hospital-acquired infections (HAIs), novel antimicrobials are warranted that are effective against HAIs and safer for human use. We hypothesize that small 5 nm size positively charged nanoparticles could specifically target bacterial cell wall and adherent fimbriae expression, serving as the next generation antibacterial agent. Herein we show highly positively charged, 5 nm amino-functionalized silver nanoparticles (NH2-AgNPs) were bactericidal; highly negatively charged, 45 nm citrate-functionalized AgNPs (Citrate-AgNPs) were nontoxic; and Ag+ ions were bacteriostatic forming honeycomb-like potentially resistant phenotype, at 10 µg Ag/mL in E. coli. Further, adherent fimbriae were expressed with Citrate-AgNPs (0.5-10 µg/mL), whereas NH2-AgNPs (0.5-10 µg/mL) or Ag+ ions (only at 10 µg/mL) inhibited fimbriae expression. Our results also showed no lipid peroxidation in human lung epithelial and dermal fibroblast cells upon NH2-AgNPs treatments, suggesting NH2-AgNPs as a biocompatible antibacterial candidate. Potent bactericidal effects demonstrated by biocompatible NH2-AgNPs and the lack of toxicity of Citrate-AgNPs lend credence to the hypothesis that small size, positively charged AgNPs may serve as a next-generation antibacterial agent, potentially addressing the rising HAIs and patient health and safety.

Preclinical efficacy and safety of novel SNAT against SARS-CoV-2 using a hamster model.

To address the unprecedented global public health crisis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we designed and developed a novel antiviral nano-drug, called SNAT (Smart Nano-Enabled Antiviral Therapeutic), comprised of taxoid (Tx)-decorated amino (NH2)-functionalized near-atomic size positively charged silver nanoparticles (Tx-[NH2-AgNPs]) that are stable for over 3 years. Using a hamster model, we tested the preclinical efficacy of inhaled SNAT on the body weight, virus titer, and histopathology of lungs in SARS-CoV-2-infected hamsters, including biocompatibility in human lung epithelium and dermal fibroblasts using lactase dehydrogenase (LDH) and malondialdehyde (MDA) assays. Our results showed SNAT could effectively reverse the body weight loss, reduce the virus load in oral swabs, and improve lung health in hamsters. Furthermore, LDH assay showed SNAT is noncytotoxic, and MDA assay demonstrated SNAT to be an antioxidant, potentially quenching lipid peroxidation, in both the human cells. Overall, these promising pilot preclinical findings suggest SNAT as a novel, safer antiviral drug lead against SARS-CoV-2 infection and may find applications as a platform technology against other respiratory viruses of epidemic and pandemic potential.

Comprehensive Phytotoxicity Assessment Protocol for Engineered Nanomaterials.

In order for nanotechnology to be sustainably applied in agriculture, emphasis should be on comprehensive assessment of multiple endpoints, including biouptake and localization of engineered nanomaterials (ENMs), potential effects on food nutrient quality, oxidative stress responses, and crop yield, before ENMs are routinely applied in consumer and agronomic products. This chapter succinctly outlines a protocol for conducting nanophytotoxicity studies focusing on nanoparticle purification and characterization, arbuscular mycorrhizal fungi (AMF)/symbiont inoculation, biouptake and translocation/localization, varied endpoints of oxidative stress responses, and crop yield.

Risk assessment of occupational exposure to anesthesia Isoflurane in the hospital and veterinary settings.

Despite the modern ventilation and waste anesthetic gas (WAG) scavenging systems, occupational exposure to common volatile anesthesia, isoflurane, can occur in the hospital and veterinary settings, but limited information exists on potential exposure and health risk of isoflurane. We assessed exposure dose rates and risks among clinicians and veterinary professionals from occupational exposure to isoflurane. Through a critical review of open literature (1965 to 2020), we summarized potential adverse effects and exposure scenarios of isoflurane among the professional groups, including anesthetists, nurses, operating room personnel, researchers, and/or veterinarians. Deterministic United States National Research Council/Environmental Protection Agency's risk assessment framework (hazard identification, dose-response relationship, exposure assessment and risk characterization) was used to compute inhalation Reference Doses (RfDs), Average Daily Doses (ADDs), and Hazard Quotient (HQ) values-an established measure of non-carcinogenic (systemic) risks-from exposure to isoflurane to workers in hospital and veterinary settings. We identified the central nervous system as the main target for isoflurane, and that isoflurane has dose-dependent effects on cardiac hemodynamics, can impair pulmonary functions and potentially cross the utero-placental barrier leading to congenital malformation in fetus. Based on the modelled RfDs (range 0.8003-7.55 mg/kg-day) and ADDs (range 0.071-1.9617 mg/kg-day), we estimated 56 different HQ values, of which 5 HQs were higher than 1 (range 1.099-2.4512) under high exposure scenarios. Our results suggest a significant non-carcinogenic risk from isoflurane exposures among workers in the occupational settings. The findings underscore the need to significantly minimize isoflurane release to protect workers' health in the hospital and veterinary environments.

Risk assessment of inhaled diacetyl from electronic cigarette use among teens and adults.

Diacetyl (C4H6O2) is a toxicant commonly found in electronic cigarettes (e-Cigs) as a flavoring component and an enhancer of e-juices. Lung injury in current and former workers in popcorn manufacturing suggests a possible association with diacetyl inhalation exposure. Although the number of e-Cig users continues to rise steadily among the teens and adults, the potential risk of pulmonary disease has not been characterized. A systematic review of the open literature identified bronchiolitis obliterans-a pathological inflammation resulting in fibrosis of the bronchioles leading to an irreversible limitation to airflow in lungs-as the primary outcome of diacetyl exposures. Following the deterministic United States National Research Council/Environmental Protection Agency's risk assessment framework, that consists of four key steps: hazard identification, dose-response assessment, exposure assessment and risk characterization, we estimated noncarcinogenic (systemic) risks using a Hazard Quotient (HQ) approach upon exposure to diacetyl among teens and adults who use e-Cigs. Based on the NIOSH Benchmark Dose (BMD; 0.0175 mg/kg-day) and modelled Average Daily Doses (ADDs; range 0.11-5.2 mg/kg-day), we estimated 12 different HQ values-a measure of non-carcinogenic risk for diacetyl inhalation exposures-all of which were greater than 1 (range 6.2875-297.1429), suggesting a significantly higher non-carcinogenic risk from diacetyl exposures among the teens and adults who use e-Cigs. These results underscore the need to regulate e-Cigs to protect teens and adults from diacetyl exposures and risk of developing lung injuries, including bronchiolitis obliterans.

A discussion about public health, lead and Legionella pneumophila in drinking water supplies in the United States.

Lead (Pb) in public drinking water supplies has garnered much attention since the outset of the Flint water crisis. Pb is a known hazard in multiple environmental matrices, exposure from which results in long-term deleterious health effects in humans. This discussion paper aims to provide a succinct account of environmental Pb exposures with a focus on water Pb levels (WLLs) in the United States. It is understood that there is a strong correlation between WLLs and blood Pb levels (BLLs), and the associated health effects. However, within the Flint water crisis, more than water chemistry and Pb exposure occurred. A cascade of regulatory and bureaucratic failures culminated in the Flint water crisis. This paper will discuss pertinent regulations and responses including their limitations after an overview of the public health effects from Pb exposure as well as discussion on our limitations on monitoring and mitigating Pb in tap water. As the Flint water crisis also included increased Legionnares' disease, caused by Legionella pneumophila, this paper will discuss factors influencing L. pneumophila growth. This will highlight the systemic nature of changes to water chemistry and public health impacts. As we critically analyze these important aspects of water research, we offer discussions to stimulate future water quality research from a new and systemic perspective to inform and guide public health decision-making.

Novel carbon nanotube (CNT)-based ultrasensitive sensors for trace mercury(II) detection in water: A review.

Infamous for "Mad hatter syndrome" and "Minamata disease", mercury (Hg) is ranked high on the Agency for Toxic Substances and Disease Registry's priority list of hazardous substances for its potent neurologic, renal, and developmental toxicities. Most typical exposures are via contaminated water and food. Although regulations and advisories are exercised at various levels, Hg pollution from both natural and anthropogenic sources has remained a major public health and safety concern. Rapid detection of solvated aqueous Hg2+ ions at low levels is critical for immediate response and protection of those who are vulnerable (young children, pregnant and breast-feeding women) to acute and chronic exposures to Hg2+. Various types of sensors capable of detecting Hg in water have been developed. In particular, the novel use of engineered carbon nanotubes (CNTs) has garnered attention due to their specificity and sensitivity towards Hg2+ detection in solution. In this focused review, we describe the sensitivity, selectivity and mechanisms of Hg2+ ion sensing at trace levels by employing CNT-based various sensor designs, and appraise the open literature on the currently applied and "proof-of-concept" methods. Five different types of CNT-based sensor systems are described: potentiometric, DNA-based fluorescence, surface plasmon resonance (SPR), colorimetric, and stripping voltammetric assays. In addition, the recognized merits and shortcomings for each type of electrochemical sensors are discussed. The knowledge from this succinct review shall guide the development of the next generation CNT-based biochemical sensors for rapid Hg2+ detection in the environment, which is a significant first step towards human health risk analysis of this legacy toxicant.

Germination and early plant development of ten plant species exposed to titanium dioxide and cerium oxide nanoparticles.

Ten agronomic plant species were exposed to different concentrations of nano-titanium dioxide (nTiO2 ) or nano-cerium oxide (nCeO2 ) (0 µg/mL, 250 µg/mL, 500 µg/mL, and 1000 µg/mL) to examine potential effects on germination and early seedling development. The authors modified a standard test protocol developed for soluble chemicals (OPPTS 850.4200) to determine if such an approach might be useful for screening engineered nanomaterials (ENMs) and whether there were differences in response across a range of commercially important plant species to 2 common metal oxide ENMs. Eight of 10 species responded to nTiO2 , and 5 species responded to nCeO2 . Overall, it appeared that early root growth may be a more sensitive indicator of potential effects from ENM exposure than germination. The observed effects did not always relate to the exposure concentration, indicating that mass-based concentration may not fully explain the developmental effects of these 2 ENMs. The results suggest that nTiO2 and nCeO2 have different effects on early plant growth of agronomic species, with unknown effects at later stages of the life cycle. In addition, standard germination tests, which are commonly used for toxicity screening of new materials, may not detect the subtle but potentially more important changes associated with early growth and development in terrestrial plants. Environ Toxicol Chem 2016;35:2223-2229. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.

Long-term sub-lethal effects of low concentration commercial herbicide (glyphosate/pelargonic acid) formulation in Bryophyllum pinnatum.

Potential long-term (~7months) sub-lethal impacts of soil-applied low levels of Roundup herbicide formulation were investigated in a greenhouse environment using the vegetative clones of succulent non-crop plant model, Bryophyllum pinnatum (Lam.) Oken. An eleven day LC50 (concentration that killed 50% of the plants) was found to be 6.25% (~1.25mg glyphosate/mL and 1.25mg pelargonic acid/mL combined), and complete mortality occurred at 12.5%, of the field application rate (i.e., ~20mg glyphosate/mL and 20mg pelargonic acid/mL as active ingredients). While sub-lethal Roundup (1-5%) exposures led to hormesis-characterized by a significant increase in biomass and vegetative reproduction, higher concentrations (≥6.25%) were toxic. A significant interaction between Roundup concentrations and leaf biomass was found to influence the F1 plantlets' biomass. Biomass asymmetry generally increased with increasing Roundup concentrations, indicating that plants were more stressed at higher Roundup treatments but within the low-dose regime (≤5% of the as-supplied formulation). While leaf apex region demonstrated higher reproduction with lower biomass increase, leaf basal area showed lower reproduction with greater biomass increase, in plantlets. The results suggest long-term exposures to drifted low levels of Roundup in soil may promote biomass and reproduction in B. pinnatum.

Preferential interaction of Na+ over K+ with carboxylate-functionalized silver nanoparticles.

Elucidating mechanistic interactions between monovalent cations (Na(+)/K(+)) and engineered nanoparticle surfaces to alter particle stability in polar media have received little attention. We investigated relative preferential interaction of Na(+) and K(+) with carboxylate-functionalized silver nanoparticles (carboxylate-AgNPs) to determine if interaction preference followed the Hofmeister series (Na(+)>K(+)). We hypothesized that Na(+) will show greater affinity than K(+) to pair with carboxylates on AgNP surfaces, thereby destabilizing the colloidal system. Destabilization upon Na(+) or K(+) interacting with carboxylate-AgNPs was evaluated probing changes in multiple physicochemical characteristics: surface plasmon resonance/optical absorbance, electrical conductivity, pH, hydrodynamic diameter, electrophoretic mobility, surface charge, amount of Na(+)/K(+) directly associated with AgNPs, and Ag(+) dissociation kinetics. We show that Na(+) and K(+) react differently, indicating local Na(+) pairing with carboxylates on AgNP surfaces is kinetically faster and remarkably favored over K(+), thus supporting Hofmeister ordering. Our results suggest that AgNPs may transform into micron-size aggregates upon release into aqueous environments and that the fate of such aggregates may need consideration when assessing environmental risk.

Particle size, surface charge and concentration dependent ecotoxicity of three organo-coated silver nanoparticles: comparison between general linear model-predicted and observed toxicity.

Mechanism underlying nanotoxicity has remained elusive. Hence, efforts to understand whether nanoparticle properties might explain its toxicity are ongoing. Considering three different types of organo-coated silver nanoparticles (AgNPs): citrate-coated AgNP, polyvinylpyrrolidone-coated AgNP, and branched polyethyleneimine-coated AgNP, with different surface charge scenarios and core particle sizes, herein we systematically evaluate the potential role of particle size and surface charge on the toxicity of the three types of AgNPs against two model organisms, Escherichia coli and Daphnia magna. We find particle size, surface charge, and concentration dependent toxicity of all the three types of AgNPs against both the test organisms. Notably, Ag(+) (as added AgNO3) toxicity is greater than each type of AgNPs tested and the toxicity follows the trend: AgNO3 > BPEI-AgNP > Citrate-AgNP > PVP-AgNP. Modeling particle properties using the general linear model (GLM), a significant interaction effect of primary particle size and surface charge emerges that can explain empirically-derived acute toxicity with great precision. The model explains 99.9% variation of toxicity in E. coli and 99.8% variation of toxicity in D. magna, revealing satisfactory predictability of the regression models developed to predict the toxicity of the three organo-coated AgNPs. We anticipate that the use of GLM to satisfactorily predict the toxicity based on nanoparticle physico-chemical characteristics could contribute to our understanding of nanotoxicology and underscores the need to consider potential interactions among nanoparticle properties when explaining nanotoxicity.

Impacts of select organic ligands on the colloidal stability, dissolution dynamics, and toxicity of silver nanoparticles.

Key understanding of potential transformations that may occur on silver nanoparticle (AgNP) surface upon interaction with naturally ubiquitous organic ligands (e.g., -SH (thoil), humic acid, or -COO (carboxylate)) is limited. Herein we investigated how dissolved organic carbon (DOC), -SH (in cysteine, a well-known Ag(+) chelating agent), and -COO (in trolox, a well-known antioxidant) could alter the colloidal stability, dissolution rate, and toxicity of citrate-functionalized AgNPs (citrate-AgNPs) against a keystone crustacean Daphnia magna. Cysteine, DOC, or trolox amendment of citrate-AgNPs differentially modified particle size, surface properties (charge, plasmonic spectra), and ion release dynamics, thereby attenuating (with cysteine or trolox) or promoting (with DOC) AgNP toxicity. Except with DOC amendment, the combined toxicity of AgNPs and released Ag under cysteine or trolox amendment was lower than of AgNO3 alone. The results of this study show that citrate-AgNP toxicity can be associated with oxidative stress, ion release, and the organism biology. Our evidence suggests that specific organic ligands available in the receiving waters can differentially surface modify AgNPs and alter their environmental persistence (changing dissolution dynamics) and subsequently the toxicity; hence, we caveat to generalize that surface modified nanoparticles upon environmental release may not be toxic to receptor organisms.