Co–N ₄ -Coordinated Single-Atom Nanozymes with Dual Bactericidal-Regenerative Functions: Overcoming Tetracycline Resistance through Self-Enhanced Oxidase-Mimicking Catalysis

Antibiotic therapy is the current option for wound healing; however, this strategy will bring about serious antibiotic resistance. Herein, a Co-N-C single-atom nanozyme with oxidase mimicking properties (calculated <i>K</i>_m value, 0.224 mM) was synthesized instead of traditional antibiotics in wound healing, which was evaluated using four tetracycline-resistant bacteria as representative indicators. Our experimental system achieved >99% eradication of all tested tetracycline-resistant bacterial strains. Besides, bacterial damage investigation confirmed that Co-N-C exerted its bactericidal effect by releasing ROS. Moreover, Co-N-C-treated wounds achieved complete re-epithelialization with restored skin appendages by day 10, whereas vehicle controls exhibited only partial wound closure (52.4 ± 5.8% area reduction) with persistent fibrinous exudate. Consequently, the investigations conducted in vitro and in vivo showed that Co-N-C SAzyme possesses excellent antibacterial activity as well as the ability to promote wound healing, demonstrating encouraging uses in wound healing and antimicrobial applications. Furthermore, a cycling inhibition assay with Co-N-C, gentamicin, and kanamycin also revealed Co-N-C's ability to inhibit tetracycline-resistant bacteria and delay resistance development. The overall result indicated that Co-N-C is an effective metal antibacterial agent and has a lot of promise for use in human health and environmental applications.