Cinnamaldehyde-derived doped carbon dots induce multifaceted antibacterial activity for robust anti-infection without acquired resistance.

The growing threat of drug-resistant pathogens calls for non-antibiotic strategies to combat prevalent superbugs. Ferroptosis, a cell death pathway driven by iron accumulation and lipid peroxidation, has recently attracted interest for its potential occurrence in bacteria. In this study, we developed a multifunctional nanoplatform: nitrogen and iron co-doped cinnamaldehyde-derived carbon dots (N,Fe-CA-CDs). In vitro, N,Fe-CA-CDs at 32 μg/mL completely eliminated bacterial colonies on agar plates, demonstrating potent bactericidal activity. The nanoplatform disrupted biofilm structure, inhibited virulence factor expression, and did not induce acquired drug resistance. Transcriptomic and metabolomic analyses further revealed that N,Fe-CA-CDs perturb energy metabolism and redox homeostasis, thereby suppressing bacterial growth, biofilm formation, and drug resistance. These findings provide a molecular basis for the mechanism of N,Fe-CA-CDs as a quorum sensing (QS) inhibitor and ferroptosis inducer. In a methicillin-resistant Staphylococcus aureus (MRSA) infection model, N,Fe-CA-CDs can strengthen bacterial interaction, induce ferroptosis-like processes, inhibit QS, alleviated wound inflammation, and robustly cleared pathogens. Overall, N,Fe-CA-CDs hold great promise for addressing antibiotic resistance and offer a novel approach for developing next-generation antimicrobial alternatives.