Infections by the gram-negative bacterium Pseudomonas aeruginosa are on the rise, and its antibiotic resistance is a tough challenge for clinical therapeutics worldwide. Therefore, it is an urgent to find alternative antibiotics that possess preferable bactericidal efficiency and are safer than silver (Ag) nanoparticles (Ag NPs). Here, we synthesized small palladium@copper (Pd_1.9Cu) alloy NPs with preferable antibacterial functions. We also used a bacteria-infected skin wound mouse model to confirm the sterilization effect of Pd_1.9Cu NPs. Pd_1.9Cu NPs killed P. aeruginosa at a low concentration, displaying a more powerful bactericidal effect than Ag NPs in vitro. In addition, Pd_1.9Cu NPs broke through the bacterial membrane, leading to DNA fragmentation and leakage of genomic DNA and proteins. The underlying mechanism was to trigger the burst of intracellular reactive oxygen species generation and accelerated ion release (Cu and Pd). Pd_1.9Cu NPs were also more capable of disinfection than Ag NPs and ceftazidime in vivo, promoting speedy wound recovery. Simultaneously, the biocompatibility of Pd_1.9Cu NPs was satisfactory both in vitro and in vivo. These results show that Pd_1.9Cu NPs are a promising nanomedicine to treat P. aeruginosa infection.

革兰氏阴性细菌铜绿假单胞菌的感染呈上升趋势，其抗生素耐药性是全球临床治疗面临的严峻挑战。因此，迫切需要找到具有更好杀菌效率且比银 (Ag) 纳米粒子 (Ag NPs) 更安全的替代抗生素。在这里，我们合成了具有较好抗菌功能的小型钯@铜（Pd _1.9 Cu）合金纳米颗粒。我们还使用细菌感染的皮肤伤口小鼠模型来确认 Pd _1.9 Cu NPs的灭菌效果。Pd _1.9 Cu NPs 可以在低浓度下杀死铜绿假单胞菌，在体外表现出比 Ag NPs 更强大的杀菌作用。此外，Pd _1.9Cu NPs 突破细菌膜，导致 DNA 断裂和基因组 DNA 和蛋白质的泄漏。潜在的机制是触发细胞内活性氧生成和加速离子释放（Cu 和 Pd）的爆发。在体内，Pd _1.9 Cu NPs 也比 Ag NPs 和头孢他啶更能消毒，促进伤口快速恢复。同时，Pd _1.9 Cu NPs 的体外和体内生物相容性均令人满意。这些结果表明，Pd _1.9 Cu NPs 是一种很有前途的纳米药物，可用于治疗铜绿假单胞菌感染。