Ultrasound-responsive catalytic microbubbles enhance biofilm elimination and immune activation to treat chronic lung infections.

Abstract

Efficient treatment of chronic lung infections caused by <i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> biofilms. In these microbubbles, piperacillin and Fe₃O₄ 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 Fe₃O₄ nanoparticles and piperacillin into the biofilm. Then, Fe₃O₄ nanoparticles chemically degrade the biofilm matrix and kill the bacteria with the assistance of piperacillin. Fe₃O₄ 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.