Ultrasound-Activatable Phase-Shift Nanoparticle as a Targeting Antibacterial Agent for Efficient Eradication of<i>Pseudomonas aeruginosa</i>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 <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) and thereby contributing to persistently chronic infections. As such, it is critical to develop a robust antimicrobial strategy capable of effectively eradicating <i>P. aeruginosa</i> biofilms and to further address aggressive clinical infection. In this study, ultrasound-activatable targeted nanoparticles were designed by using poly(lactic-<i>co</i>-glycolic acid) (PLGA) nanoparticles to encapsulate phase-transformable perfluoropentane (PFP) and the antibiotic meropenem via a double emulsion approach, followed by conjugation with anti-<i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> directly and accelerate the associated wound healing. These nanoparticles eradicated biofilms effectively and cleared bacteria <i>in vitro</i> as well as exhibited potent anti-infective activity <i>in vivo</i>. In summary, this study demonstrates the efficacy of a sonobactericidal strategy as a means of effectively and reliably eliminating biofilms.