Concentration Ranges of Antibacterial Cations for Showing the Highest Antibacterial Efficacy but the Least Cytotoxicity against Mammalian Cells: Implications for a New Antibacterial Mechanism

Abstract

Antibacterial metal ions, such as Ag+, Zn2+ and Cu2+, have been extensively used in medical implants and devices due to their strong broad spectrum of antibacterial activity. However, it is still a controversial issue as to whether they can show the desired antibacterial activity while being toxic to mammalian cells. It is very important to balance their antibacterial effectiveness with minimal damage to mammalian cells. Toward this end, this study is to identify the suitable concentrations of these three ions at which they can effectively kill two types of clinically relevant bacteria (Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)) but show no obvious cytotoxicity on fibroblasts. Such concentration ranges are found to be 2.5 × 10−7 M–10−6 M, 10−5 M–10−4 M, and 10−5 M–10−4 M for Ag+, Zn2+, and Cu2+, respectively. Investigation of their antibacterial mechanism shows that these three metal ions all show antibacterial property through a mechanism of damaging bacterial cell membranes by the generation of reactive oxygen species but surprisingly preserving the integrity of bacterial genomic DNA. The encouraging results indicate that antibacterial metal ions with controlled concentrations can bring considerable benefits to biomedical applications.

Multifunctional Copper-Containing Carboxymethyl Chitosan/Alginate Scaffolds for Eradicating Clinical Bacterial Infection and Promoting Bone Formation

“…Moreover, the amount of Cu 2+ ions (Figure 1f) released from the CMC/Alg/Cu made with this concentration of Cu nanoparticles was within the best concentration range of Cu 2+ ions according to our previous research. 38 Hence, the prepared CMC/Alg/Cu scaffolds possessed good biocompatibility with no significant cytotoxic effect on MC3T3-E1 cells and no hemolysis to human red blood cells.…”

Rational Design of Biomolecular Templates for Synthesizing Multifunctional Noble Metal Nanoclusters toward Personalized Theranostic Applications

“…Other than the desirable features of metal NCs for imaging, sensing and delivery, metal NCs have also been widely used for therapeutic applications. Much work has revolved around harnessing the metal core of NCs for therapeutic applications such as radiotherapy, photodynamic therapy[18b,78] and antibacterial therapy . However, in this paper, we will focus on the current designs of biomolecular ligand shells comprising of nucleic acids, proteins and peptides for therapies.…”

“…The emission color and QY can be controlled by varying the reaction conditions . [79b,108] However, these system‐specific conditions are not universal and cannot be used as guidelines to instruct the control of emission color. A more rational approach should involve the systematic design of the biotemplates containing the essential functional moiety to control the photoluminescence properties of metal NCs.…”

Zinc‐oxide nanoparticles act catalytically and synergistically with nitric oxide donors to enhance antimicrobial efficacy

“…20 Zinc oxide is another antimicrobial agent but it is already commercially used and is known to have less cytotoxicity toward mammalian cells while having similar antibacterial effects at the same concentration when compared to other commonly used antimicrobial metal ions such as copper and silver. 21 It inhibits the growth of dental caries-related bacteria, Streptococcus mutans, Actinomyces viscosus, Lactobacillus casei, Staphylococcus aureus (S. aureus), and Candida albicans. 22 Zinc oxide nanoparticles (ZnO-NPs) have been found to inhibit growth and cause loss of cell viability in Escherichia coli (E. coli) and S. aureus at concentrations ranging from as low as 1 mM up to 3.4 mM.…”