Screening Small Metabolites from Cells as Multifunctional Coatings Simultaneously Improves Nanomaterial Biocompatibility and Functionality.

Currently, nanomaterials face a dilemma due to their advantageous properties and potential risks to human health. Here, a strategy to improve both nanomaterial biocompatibility and functionality is established by screening small metabolites from cells as nanomaterial coatings. A metabolomics analysis of cells exposed to nanosilver (nAg) integrates volcano plots (t-tests and fold change analysis), partial least squares-discriminant analysis (PLS-DA), and significance analysis of microarrays (SAM) and identifies six metabolites (l-aspartic acid, l-malic acid, myoinositol, d-sorbitol, citric acid, and l-cysteine). The further analysis of cell viability, oxidative stress, and cell apoptosis reveals that d-sorbitol markedly reduces nAg cytotoxicity. Subsequently, small molecule loading, surface oxidation, and ionic release experiments support d-sorbitol as the optimal coating for nAg. Importantly, d-sorbitol loading improves the duration of the antibacterial activity of nAg against Escherichia coli and Staphylococcus aureus. The biocidal persistence of nAg-sorbitol is extended beyond 9 h, and the biocidal effects at 12 h are significantly higher than those of naked nAg. This work proposes a new strategy to improve the biocompatibility and functionality of nAg simultaneously by screening small metabolites from cells as nanomaterial functional coatings, a method that can be applied to mitigate the side effects of other nanomaterials.