State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing210023, China.
Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
ACS Nano. 2024 Jun 11;18(23):15204-15217. doi: 10.1021/acsnano.4c03527. Epub 2024 May 27.
The biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.
生物膜不仅在难治性慢性肺部感染中发展出了高度的抗微生物药物耐受性，还会引发异常的宿主炎症反应。代谢状态在细菌对抗微生物药物的敏感性和免疫细胞的炎症反应中都起着至关重要的作用，因此提供了一个潜在的治疗靶点。在这里，我们描述了一种代谢调节策略，使用含有声敏剂和缺氧激活前药的超声响应脂质体纳米颗粒来对抗生物膜相关的慢性肺部感染。在超声刺激下，声敏剂通过耗氧产生具有抗菌作用的活性氧物质。随后，耗氧介导的缺氧不仅诱导细菌进行无氧代谢以激活抗生素，还触发免疫细胞的糖酵解途径以引发炎症激活。这种代谢调节策略在小鼠模型中对生物膜诱导的慢性肺部感染表现出了高效的治疗效果，为对抗生物膜相关的慢性感染提供了一种有前途的方法。
