Metabolic Labeling Mediated Targeting and Thermal Killing of Gram‐Positive Bacteria by Self‐Reporting Janus Magnetic Nanoparticles

Nanoparticles have been widely used in detection and killing of bacteria; however, targeting bacteria is still challenging. Delicate design of nanoparticles is required for simultaneous targeting, detection, and therapeutic functions. Here the use of Au/MnFe2O4 (Au/MFO) Janus nanoparticles to target Gram‐positive bacteria via metabolic labeling is reported and realize integrated self‐reporting and thermal killing of bacteria. In these nanoparticles, the Au component is functionalized with tetrazine to target trans‐cyclooctene group anchored on bacterial cell wall by metabolic incorporation of d‐amino acids, and the MFO part exhibits peroxidase activity, enabling self‐reporting of bacteria before treatment. The spatial separation of targeting and reporting functions avoids the deterioration of catalytic activity after surface modification. Also important is that MFO facilitates magnetic separation and magnetic heating, leading to easy enrichment and magnetic thermal therapy of labeled bacteria. This method demonstrates that metabolic labeling with d‐amino acids is a promising strategy to specifically target and kill Gram‐positive bacteria. Tetrazine‐functionalized Janus magnetic nanoparticles are developed to target trans‐cyclooctene‐labeled peptidoglycans of Gram‐positive bacteria that are specifically tagged via metabolic labeling with d‐amino acid. The magnetic nanoparticles exhibit peroxidase activity, which produces colorimetric signals to offer a self‐reporting method. The magnetic separation and magnetic heating empower the nanoparticles to eradicate the nanoparticle‐labeled bacteria with log reductions as high as three.