Cluster Materials as Traceable Antibacterial Agents

Abstract

ConspectusThe precise design of nanomaterials is essential for both basic and applied materials research. However, it is difficult to precisely synthesize and manipulate nanomaterials with adjustable physicochemical properties and functions at the molecular and atomic levels. For example, the emerging precision nanomedicine requires not only the precise design of nanomaterials (or atomically precise nanochemistry) but also real-time observations of the theranostic process. Metal nanoclusters (NCs) are molecule-like metal nanomaterials with well-defined molecular formulas, structures, and properties, which can meet the above requirements. Metal NCs can be easily synthesized and manipulated, and they have strong luminescence properties, which can be used to monitor biomedical processes under working conditions and environments. Moreover, unlike metal nanoparticles and other molecules, the core (i.e., size (number of metal atoms in each NC) and composition) and surface of metal NCs can be individually adjusted at the atomic level. The atomic-level tailoring of metal NCs has a significant impact on their physicochemical properties and further applications. In addition, the atomic-level control of metal NCs can also help us to understand the respective functions of metal NCs in biomedical applications at the molecular and atomic levels. This knowledge will facilitate the accurate screening and design of metal NCs, with the desired functions and required efficacy to realize precision nanomedicine.In this Account, we focus on the design of antibacterial agents based on atomically precise metal NCs. We first discuss the antibacterial mechanisms of gold (Au) and silver (Ag) NCs, which can induce the production of reactive oxygen species (ROS) inside the bacteria to achieve the killing effect. Au nanomaterials are generally regarded as noble and nonantibacterial, but ultrasmall Au NCs can show good (and unexpected) antibacterial ability. In addition, the luminescent Au NCs can be used as traceable antibacterial agents to monitor real-time interactions with bacteria. Moreover, we can individually engineer the core (i.e., size and composition) and surface of metal NCs at the atomic level. We have constructed three libraries of metal NCs with different physicochemical properties: Au NCs with the same surface but different sizes, (AuAg)25 alloy NCs with the same surface but different compositions, and Au25 NCs with different surfaces. Through these libraries, we conclude that the core size of metal NCs would not affect the antibacterial ability, but the composition of the metal core and the surface ligands of metal NCs would greatly influence their antibacterial efficacy. In turn, this allows us to understand the killing mechanism of antibacterial materials at the molecular level, which is conducive to the design of antibacterial agents with controllable effects. In addition, the surface of metal NCs can be combined with a second antibacterial agent with a different working mechanism to achieve an enhanced synergistic antibacterial effect. Successful examples include Ag NCs with commercial antibiotics and Au NCs with two-dimensional (2D) nanomaterials (e.g., graphene oxide (GO) and MXene nanosheets). This Account is concluded with our perspectives on the future development of atomically precise nanochemistry in the design of antibacterial agents and other theranostic agents. The systematic study of antibacterial metal NCs can also serve as a good paradigm for understanding precision nanomedicine at the molecular level from the aspects of both materials and biomedicine.