Emerging investigator series: it's not all about the ion: support for particle-specific contributions to silver nanoparticle antimicrobial activity†
Silver nanoparticles (AgNPs) and other ionizing engineered nanomaterials (ENMs) are candidates for the development of antimicrobial agents due to their efficacy, multiple modes of bacterial inactivation, and tunability with respect to both the magnitude and mechanisms of antimicrobial activity. Exploiting this versatility requires elucidating the bacterial inactivation pathway(s) of the ENM, and in particular, the link between material properties and the desired biological endpoint. The mechanisms of antimicrobial activity for macrosilver, Ag salts, and AgNPs have been widely studied, and largely attribute this activity to the release of Ag ions via oxidation and dissolution of the surface Ag atoms. However, it has also been established that Ag ion exposure alone does not elicit the same bacterial response as exposure to AgNPs, which suggests that the observed antimicrobial activity is induced not only by solubilized ions but also by the ENM itself. Resolving the role of the AgNP is critical to informing design of nano-enabled antimicrobials a priori. Herein, we present a systematic review of the AgNP antimicrobial activity literature and specifically focus on studies that scale Ag ion controls to the likely quantities of bioavailable Ag released from AgNPs. This literature selection criterion reveals the critical role of scaled ion controls in distinguishing ion and particle contributions to the observed antimicrobial activity. Overall, our analysis of this literature indicates that in most cases of bacteria exposure to AgNPs, particle-specific activity is observed and acts in concert with and/or independently from solubilized Ag ions alone. These results are exciting and suggest that more efficacious Ag- and ENM-enabled antimicrobials can be obtained through ENM design.