Quaternary ammonium-functionalized carbon quantum dots with low drug resistance inhibit biofilm formation and accelerate infected wound healing.
The growing threat of bacterial adaptive resistance against nanomaterials necessitates an in-depth understanding of the molecular mechanisms underlying nano-bactericidal effects. Carbon quantum dots (CQDs) have emerged as promising functional nanomaterials for bioimaging, biosensing and biomedical detection, whereas high-performance CQDs eliminating drug-resistant bacterial infections remain greatly limited. Herein, quaternized tartaric acid-based carbon quantum dots (TDAQDs) with prominent antibacterial potency and strong ability to restrict bacterial drug resistance were synthesized using tartaric acid and diallyldimethylammonium chloride (DDA). The average particle diameter (1.21 nm), zeta potential measurement (+35.5 mV), and the MIC (at 5 μg/mL for S. aureus and clinical multidrug-resistant MRSA, and 15 μg/mL for E. coli) were the core quantitative physicochemical and biological parameters of TDAQDs. TDAQDs bind to bacteria through electrostatic interaction and induce reactive oxygen species overproduction, which disrupts bacterial membrane structure and triggers massive cytoplasmic leakage. TMT-based quantitative proteomics analysis revealed that TDAQDs markedly disturbed core biological pathways of S. aureus, including ribosome function, RNA degradation and substance metabolism, while suppressing ABC transporter-associated bacterial pathogenic processes. In vivo wound healing quantification illustrated superior therapeutic performance (91.35% and 88.88% for S. aureus and E. coli-infected wounds), confirming prominent infection elimination and accelerated skin regeneration in TDAQDs-treated groups. In vitro and in vivo biosafety tests verified the good biocompatibility of TDAQDs with negligible cytotoxicity to H9C2 cells, erythrocytes and major mouse organs. Collectively, these findings establish TDAQDs as a robust, biocompatible nanoplatform that simultaneously combats drug-resistant bacteria and mitigates resistance evolution, representing a meaningful step toward developing next-generation antimicrobial strategies to address the global crisis of antibiotic failure.