The increasing prevalence of antimicrobial resistance in Staphylococcus aureus necessitates alternative therapeutic approaches. Neutrophils play a crucial role in the fight against S. aureus but suffer from deficiencies in function leading to increased infection. Here we report a nanoparticle-mediated immunotherapy aimed at potentiating neutrophils to eliminate S. aureus. The nanoparticles consist of naftifine, haemoglobin (Hb) and a red blood cell membrane coating. Naftifine disrupts staphyloxanthin biosynthesis, Hb reduces bacterial hydrogen sulfide levels and the red blood cell membrane modifies bacterial lipid composition. Collectively, the nanoparticles can sensitize S. aureus to host oxidant killing. Furthermore, in the infectious microenvironment, Hb triggers lipid peroxidation in S. aureus, promoting neutrophil chemotaxis. Oxygen supplied by Hb can also significantly enhance the bactericidal capability of the recruited neutrophils by restoring neutrophil respiratory burst via hypoxia relief. This multimodal nanoimmunotherapy demonstrates excellent therapeutic efficacy in treating antimicrobial-resistant S. aureus persisters, biofilms and S. aureus-induced infection in mice.

金黄色葡萄球菌耐药性日益普遍，需要替代治疗方法。中性粒细胞在对抗金黄色葡萄球菌方面发挥着至关重要的作用，但其功能缺陷导致感染增加。在这里，我们报告了一种纳米颗粒介导的免疫疗法，旨在增强中性粒细胞以消除金黄色葡萄球菌。纳米颗粒由萘替芬、血红蛋白 (Hb) 和红细胞膜涂层组成。萘替芬会破坏葡萄球菌黄素的生物合成，血红蛋白会降低细菌的硫化氢水平，并且红细胞膜会改变细菌的脂质成分。总的来说，纳米颗粒可以使金黄色葡萄球菌对宿主氧化剂杀死敏感。此外，在感染性微环境中，血红蛋白触发金黄色葡萄球菌中的脂质过氧化，促进中性粒细胞趋化性。 Hb 提供的氧气还可以通过缓解缺氧来恢复中性粒细胞的呼吸爆发，从而显着增强招募的中性粒细胞的杀菌能力。这种多模式纳米免疫疗法在治疗小鼠体内耐药金黄色葡萄球菌持续存在、生物膜和金黄色葡萄球菌引起的感染方面表现出优异的治疗效果。