Colorimetric/Fluorescent/SERS/Gas Pressure Four-Modal Sensing and Killing of Bacteria via Enzyme-Responsive Aggregation of Nanoparticles

Many diseases are associated with bacterial infections, and the detection and treatment of bacteria are critically important. To date, integrating multimodal bacterial detection and treatment into a single platform remains a challenge. In this work, we developed a colorimetric, fluorescent, surface-enhanced Raman scattering and gas pressure sensing four-modal platform, AuNPs-Peptide-Rh 123 (APR), for bacterial detection and killing. The APR consists of gold nanoparticles (AuNPs), an alkaline phosphatase (ALP) responsive peptide (CF₄KY^P), and Rhodamine 123 (Rh 123). In the absence of bacteria, the APR solution appears wine-red, the green fluorescence of Rh 123 is quenched by AuNPs via fluorescence resonance energy transfer, the Raman signal of Rh 123 is enhanced, and APR cannot catalyze the decomposition of hydrogen peroxide (H₂O₂) to produce oxygen (O₂). Upon encountering bacteria, the ALP of bacteria triggers the in situ aggregation of APR on bacterial membranes and causes the detachment of Rh 123. This results in a color change from wine-red to colorless, restoration of Rh 123 fluorescence, and a decrease in Raman signal intensity. Interestingly, the in situ aggregation of APR leads to the destruction of bacterial membranes, leakage of substances, and death of bacteria. The release of endogenous catalase from damaged bacteria can catalyze the decomposition of H₂O₂ to produce O₂, thus realizing the detection of bacteria by gas pressure sensing. APR has excellent biocompatibility and shows a good antibacterial effect on bacterial-infected wounds. This work demonstrates the potential of enzyme-responsive multifunctional nanoplatforms for multimodal detection and treatment of pathogenic microorganisms.