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

Abstract 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.