Ultrasound-Activatable Phase-Shift Nanoparticle as a Targeting Antibacterial Agent for Efficient Eradication of Pseudomonas aeruginosa Biofilms.

Abstract

Biofilms are physical barriers composed of extracellular polymeric substances (EPS) that enable planktonic bacteria to resist host responses and antibacterial treatments, complicating efforts to clear bacteria such as Pseudomonas aeruginosa (P. aeruginosa) and thereby contributing to persistently chronic infections. As such, it is critical to develop a robust antimicrobial strategy capable of effectively eradicating P. aeruginosa biofilms and to further address aggressive clinical infection. In this study, ultrasound-activatable targeted nanoparticles were designed by using poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate phase-transformable perfluoropentane (PFP) and the antibiotic meropenem via a double emulsion approach, followed by conjugation with anti-P. aeruginosa antibodies. In this strategy, ultrasound exposure can trigger PFP to produce microbubbles, inducing ultrasonic cavitation effects that can disrupt EPS components and allow nanoparticles to release meropenem to kill P. aeruginosa directly and accelerate the associated wound healing. These nanoparticles eradicated biofilms effectively and cleared bacteria in vitro as well as exhibited potent anti-infective activity in vivo. In summary, this study demonstrates the efficacy of a sonobactericidal strategy as a means of effectively and reliably eliminating biofilms.