Du Chunhong, Wang Shuai, Cheng Yijie, Li Jie, Zhang Yufei, Li Zhuohao, Zhu Baolin, Wu Zhongming, Zhang Xinge, Zhou Lingyi
Department of Blood Transfusion, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
J Nanobiotechnology. 2025 Sep 26;23(1):607. doi: 10.1186/s12951-025-03676-5.
Pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) infection remains a formidable clinical challenge due to persistent biofilm formation and intrinsic antibiotic resistance, exacerbated by bacterial iron homeostasis that stabilizes biofilm architecture and neutralizes oxidative stress. Herein, we present Fe/TNT@NM, a biomimetic nanosonosensitizer activated by ultrasound (US) to dismantle biofilms through dual extracellular-intracellular mechanisms. The nanosonosensitizer features an iron-doped titanate nanotube (Fe/TNT) core encapsulated within a neutrophil membrane (NM). Under US irradiation, Fe/TNT@NM generates sonodynamic reactive oxygen species (ROS) extracellularly and enhances Fe release. These ions catalyze the Fenton reaction extracellularly to amplify chemodynamic effects and disrupt intracellular iron homeostasis, triggering bacterial ferroptosis. The NM coating enables immune evasion and biofilm-targeted delivery. This ultrasound-reinforced ferroptosis strategy synchronizes extracellular ROS storms with intracellular iron dyshomeostasis, achieving dual-action biofilm dismantling and eradication of drug-resistant P. aeruginosa. In a murine pneumonia model, Fe/TNT@NM suppresses biofilms and mitigates pulmonary injury. By converging biomimetic targeting, sonodynamic-chemodynamic cascades, and ultrasound-augmented ferroptosis, this nanosonosensitizer presents a paradigm-shifting approach to combat refractory biofilm infections and antibiotic resistance.
由铜绿假单胞菌（P. aeruginosa）感染引起的肺炎仍然是一个严峻的临床挑战，因为其会持续形成生物膜并具有内在的抗生素耐药性，而细菌铁稳态会稳定生物膜结构并中和氧化应激，从而加剧这种情况。在此，我们展示了Fe/TNT@NM，一种由超声（US）激活的仿生纳米声敏剂，可通过细胞外 - 细胞内双重机制拆解生物膜。该纳米声敏剂的特征是包裹在中性粒细胞膜（NM）内的铁掺杂钛酸纳米管（Fe/TNT）核心。在超声照射下，Fe/TNT@NM在细胞外产生活性氧（ROS）并增强铁释放。这些离子在细胞外催化芬顿反应以放大化学动力学效应并破坏细胞内铁稳态，引发细菌铁死亡。NM涂层可实现免疫逃逸和生物膜靶向递送。这种超声增强的铁死亡策略将细胞外ROS风暴与细胞内铁稳态失衡同步，实现双重作用的生物膜拆解并根除耐药性铜绿假单胞菌。在小鼠肺炎模型中，Fe/TNT@NM可抑制生物膜并减轻肺损伤。通过融合仿生靶向、声动力 - 化学动力级联反应和超声增强的铁死亡，这种纳米声敏剂为对抗难治性生物膜感染和抗生素耐药性提供了一种范式转变的方法。
