The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of −5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (¹O₂) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.

由过度使用抗生素引起的耐药细菌感染的治疗仍然是全球面临的严峻挑战。在此，制备了两性离子电荷可转换介观二氧化硅/多肽杂化纳米粒子（MSPNs），用于协同化学光动力疗法治疗耐药细菌感染。随后，将阿奇霉素（AZT）和亚甲蓝（MB）加载到MSPNs中，形成组合的化学-光动力治疗纳米颗粒（MSPNs-AZT/MB），用于治疗耐甲氧西林金黄色葡萄球菌（MRSA ））。值得注意的是，所制备的 MSPNs-AZT/MB 在生理 pH 下表现出 -5.2 mV 的负表面电荷，而在酸性环境中转变为 24.7 mV 的正表面电荷，导致与细菌表面的结合增强。脂肪酶触发的 AZT 释放高达 77.9%，负载的 MB 证明了用于光动力治疗的有效单线态氧 ( ¹ O ₂ ) 生成。体外实验结果显示对MRSA具有优异的抗菌作用在浮游生物和生物膜表型中。此外，与小鼠模型中的单一疗法相比，所制备的 MSPNs-AZT/MB 表现出高达 94% 的协同和增强的抗菌感染效果。考虑到上述优点，所制备的化学-光动力联合治疗纳米粒子显示出良好的生物相容性和有效治疗耐药细菌的临床潜力。