Citation: Ameh, T.; Gibb, M.; Stevens, D.; Pradhan, S.H.; Braswell, E.; Sayes, C.M. Silver and Copper Nanoparticles Induce Oxidative Stress in Bacteria and Mammalian Cells. Nanomaterials 2022, 12, 2402. https://doi.org/10.3390/ nano12142402 Academic Editor: Zili Sideratou Received: 6 May 2022 Accepted: 12 July 2022 Published: 14 July 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nanomaterials Article Silver and Copper Nanoparticles Induce Oxidative Stress in Bacteria and Mammalian Cells Thelma Ameh 1 , Matthew Gibb 2 , Dinny Stevens 1 , Sahar H. Pradhan 1 , Evan Braswell 3 and Christie M. Sayes 1,2, * 1 Department of Environmental Science, Baylor University, Waco, TX 76798, USA; thelma_ameh1@baylor.edu (T.A.); dinny_stevens1@baylor.edu (D.S.);sahar_pradhan@baylor.edu (S.H.P.) 2 Institute of Biomedical Studies, Baylor University, Waco, TX 76798, USA; matthew_gibb@baylor.edu 3 Mission Laboratory, United States Department of Agriculture, Animal and Plant Health Inspection Service, Plant Protection and Quarantine, Science and Technology, Edinburg, TX 78541, USA; evan.braswell@usda.gov * Correspondence: christie_sayes@baylor.edu; Tel.: +1-254-710-3469 Abstract: Silver and copper nanoparticles (AgNPs and CuNPs) coated with stabilizing moieties induce oxidative stress in both bacteria and mammalian cells. Effective antibacterial agents that can overcome existing mechanisms of antibacterial resistance will greatly improve biomedical interven- tions. In this study, we analyzed the effect of nanoparticle-induced stress. Escherichia coli and normal human bronchial epithelial (BEAS-2B) cells were selected for this study. The nanoparticle constructs tested showed low toxicity to mammalian cells except for the polyvinylpyrrolidone-surface-stabilized copper nanoparticles. In fact, both types of copper nanoparticles used in this study induced higher levels of reactive oxygen species than the surface-stabilized silver nanoparticles. In contrast to mammalian cells, the surface-stabilized silver and copper nanoparticles showed varying levels of toxicity to bacteria cells. These data are expected to aid in bridging the knowledge gap in differential toxicities of silver and copper nanoparticles against bacteria and mammalian cells and will also improve infection interventions. Keywords: cetyltrimethylammonium bromide; polyvinyl pyrrolidone; reactive oxygen species; metal ion; E. coli; BEAS-2B 1. Introduction Effective antibacterial agents that can overcome existing mechanisms of antibacterial resistance will greatly improve biomedical interventions [1,2]. To address this challenge, metal-based nanomaterials are extensively studied in terms of antibacterial properties. For example, silver nanoparticles (AgNPs) and copper nanoparticles (CuNPs) have been coated with polymers to improve particle stability and have shown toxicities in both bacteria and mammalian cells [3–9]. However, the modes of toxicological action by which these nanopar- ticles induce stress are speculative, and have not been clearly demonstrated. There are three main working hypotheses. First, AgNPs and CuNPs induce toxicity through metal-ion leaching resulting in soluble metal ions that can directly interact with cells and induce cyto- toxicity [10]. Second, these nanoparticles induce toxicity through reactive-oxygen-species (ROS) generation and subsequent oxidative stress [11]. Third, non-oxidative mechanisms, such as cell membrane permeability disruption can induce cell death [12]. Toxic modes of action from nanoparticle exposure in different cell types can occur simultaneously or independent of one another, but most exposure scenarios lead to cell death [13,14]. There- fore, it is important to characterize the specific modes of nanoparticle toxicity in different cell types. Metal ions that leach from nanoparticles can serve as effective antibacterial agents capable of combating antibiotic resistance because the presumed mode of action is sig- nificantly different from that of conventional antibiotics (which target cell wall assembly, Nanomaterials 2022, 12, 2402. https://doi.org/10.3390/nano12142402 https://www.mdpi.com/journal/nanomaterials