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, Nanjing 210023, China.
Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, China.
Sci Adv. 2023 Jan 25;9(4):eade5446. doi: 10.1126/sciadv.ade5446.
Efficient treatment of chronic lung infections caused by biofilms is a great challenge because of drug tolerance and immune evasion issues. Here, we develop ultrasound-responsive catalytic microbubbles with biofilm elimination and immune activation properties to combat chronic lung infection induced by biofilms. In these microbubbles, piperacillin and FeO nanoparticles form a drug-loaded shell surrounding the air core. Under ultrasound stimulation, the microbubbles can physically disrupt the structure of biofilms and enhance the penetration of both FeO nanoparticles and piperacillin into the biofilm. Then, FeO nanoparticles chemically degrade the biofilm matrix and kill the bacteria with the assistance of piperacillin. FeO nanoparticles can activate the immune response for biofilm elimination by polarizing macrophages into a pro-inflammatory phenotype. These ultrasound-responsive catalytic microbubbles efficiently treat chronic lung infections in a mouse model by combining physical/chemical/antibiotic biofilm elimination and immune activation, thus providing a promising strategy for combating bacterial biofilm infections.
高效治疗生物膜引起的慢性肺部感染是一个巨大的挑战，因为存在药物耐受和免疫逃避问题。在这里，我们开发了具有生物膜消除和免疫激活特性的超声响应催化微泡，以对抗生物膜引起的慢性肺部感染。在这些微泡中，哌拉西林和 FeO 纳米颗粒形成负载药物的外壳，包围空气核。在超声刺激下，微泡可以物理破坏生物膜的结构，并增强 FeO 纳米颗粒和哌拉西林进入生物膜的渗透。然后，FeO 纳米颗粒在哌拉西林的辅助下，通过化学降解生物膜基质并杀死细菌。FeO 纳米颗粒可以通过将巨噬细胞极化成促炎表型来激活免疫反应以消除生物膜。这些超声响应催化微泡通过物理/化学/抗生素生物膜消除和免疫激活，有效地治疗了小鼠模型中的慢性肺部感染，为对抗细菌生物膜感染提供了一种有前途的策略。
