Contents lists available at ScienceDirect Materials Science & Engineering C journal homepage: www.elsevier.com/locate/msec Structure-activity relationship of diameter controlled Ag@Cu nanoparticles in broad-spectrum antibacterial mechanism Benjamín Valdez-Salas a,b, ⁎ , Ernesto Beltrán-Partida a,b , Roumen Zlatev c , Margarita Stoytcheva c , Daniel Gonzalez-Mendoza d , Jorge Salvador-Carlos b , Aldo Moreno-Ulloa e , Nelson Cheng f a Laboratorio de Biología Molecular y Cáncer, Instituto de Ingeniería, Universidad Autónoma de Baja California, Mexicali, Baja California, Mexico b Laboratorio de Corrosión y Materiales Avanzados, Instituto de Ingeniería, Universidad Autónoma de Baja California, Mexicali, Baja California, Mexico c Laboratorio de Biosensores y Electroquímica Aplicada, Instituto de Ingeniería, Universidad Autónoma de Baja California, Mexicali, Baja California, Mexico d Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California, Mexicali, Baja California, Mexico e Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada, Baja California, Mexico f Magna International Pte Ltd, Singapore ARTICLEINFO Keywords: Core-shell Bimetallic Antibacterial Nanoparticles Broad-spectrum Cytotoxicity Cytoviva ABSTRACT Current outbreaks associated with drug-resistant clinical strains are demanding for the development of broad- spectrum antibacterial agents. The bactericidal materials should be eco-friendly, economical and efective to suppress bacterial growth. Thus, in this work, diameter controlled spherical Cu core -Ag shell nanoparticles (Ag@CuNPs) with diameter ranging from 70 to 100 nm by one-step co-reduction approach were designed and synthesized. The Ag@CuNPs were homogenous, stable, and positively charged. The 70 nm Ag@CuNPs showed a consistent and regular Ag shielding. We observed the 100 nm Ag@CuNPs achieved symmetrical doped Ag clusters on the Cu core surface. We used Gram-positive and Gram-negative models strains to test the wide- spectrum antibacterial activity. The Ag@CuNPs showed detrimental microbial viability in a dose-dependent manner; however, 70 nm Ag@CuNPs were superior to those of 100 nm Ag@CuNPs. Initially, Ag@CuNPs at- tached and translocated the membrane surface resulting in bacterial eradication. Our analyses exhibited that antibacterial mechanism was not governed by the bacterial genre, nonetheless, by cell type, morphology, growing ability and the NPs uptake capability. The Ag@CuNPs were highly tolerated by human fbroblasts, mainly by the use of starch as glucosidic capper and stabilizer, suggesting optimal biocompatibility and activity. The Ag@CuNPs open up a novel platform to study the potential action of bimetallic nanoparticles and their molecular role for biomedical, clinical, hospital and industrial-chemical applications. 1. Introduction In recent years, there has been an increasing emergency by drug- resistant strains, severe deadly bacterial infections, and ancient diseases that are coming back due to the inefciency of currently prescribed antibiotics [1,2]. Moreover, the intensive care units are the most sus- ceptible to facing patients with poor or inadequate antibacterial ther- apeutic responses [3]. Thus, it is necessary the development of new antimicrobial therapies, with the broad-spectrum capability. An strategy to approach the role of growing danger-resistant in- fections is the development and management of antibacterial metallic nanoparticles (NPs). Silver (Ag) and copper (Cu) are metals with im- portant bactericidal properties [4,5]. On the other hand, when bulk Ag and Cu are nanostructured, the surface area to volume ratio is increased, enhancing their physicochemical and biological character- istics. Additionally, AgNPs and CuNPs have been applied for food- packaging [6], catalysis [7], textile industry [8], sensors [9], optoe- lectronics [10], and more importantly, as antimicrobial agents [11]. Diferent techniques have been reported for the synthesis of AgNPs and CuNPs. Some examples are microwave, electrolysis, and chemical re- duction [12]. Of particular interest, chemical reduction allows versatile control of the size, morphology, crystallinity, and surface chemical composition of NPs [12,13]. Furthermore, it is important to highlight that chemical reduction is a cost-efective, facile, scalable approach and it supports the use of green reagents without the need for any expensive equipment [14–16]. However, AgNPs and mostly CuNPs are extremely susceptible to the formation of oxide species (due to low stability, and high ambient oxygen reactivity), which inversely disrupts the benefcial https://doi.org/10.1016/j.msec.2020.111501 Received 8 July 2020; Received in revised form 2 September 2020; Accepted 7 September 2020 ⁎ Corresponding author at: Laboratorio de Biología Molecular y Cáncer, Instituto de Ingeniería, Universidad Autónoma de Baja California, Mexicali, Baja California, Mexico. E-mail address: benval@uabc.edu.mx (B. Valdez-Salas). Materials Science & Engineering C 119 (2021) 111501 Available online 12 September 2020 0928-4931/ © 2020 Elsevier B.V. All rights reserved. T