Synthesis of curcumin-quaternized carbon quantum dots with enhanced broad-spectrum antibacterial activity for promoting infected wound healing

With the increasing incidence of multidrug-resistant antibacterial infections worldwide, developing new antibiotics to fight bacterial infections is urgent. The natural product curcumin has favorable antioxidant and anti-inflammatory effects, but poor water solubility greatly limits its bioavailability, bioactivity and clinical application. Herein, to improve the bioactivity and enhance broad-spectrum antibacterial of curcumin, we synthesized quaternized carbon quantum dots (Q-CQDs) derived from the natural curcumin and 2,3-epoxypropyltrimethylammonium chloride (GTA) with highly solubility and stability by "double-thermal" method. It is proposed that the surfaces of Q-CQDs would still remain the active groups of curcumin and quaternary ammonium to boost the antibacterial activity. Experimental results reveal that the Q-CQDs possess excellent broad-spectrum antibacterial activity and the activity is significantly higher than that of natural curcumin. Investigation of the antibacterial mechanism of Q-CQDs showed that Q-CQDs functionalized with -N+(CH3)3 had strong adherence behavior on the bacterial cell membrane. Like a "Trojan Horse", the bacterial cells lost their integrity, and the entry of Q-CQDs caused ROS generation and the efflux of cytoplasmic DNA and RNA, leading to the death of bacteria. The bacterial resistance of Q-CQDs was not observed, and Q-CQDs did not cause hemolysis and cytotoxicity. In vivo, the S. aureus-infected wounds, E. coli-infected wounds and mixed bacteria infected wounds healing tests with mice model indicate that Q-CQDs inhibited the bacterial population at the wound site, reduced inflammation and promoted wound healing. These results suggested that the Q-CQDs are a potential antibacterial candidate for clinical infected-wound healing applications and even bacteria resistant infections.