Ultrasound-Activatable Phase-Shift Nanoparticle as a Targeting Antibacterial Agent for Efficient Eradication ofPseudomonas aeruginosaBiofilms

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.

Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment

“…Xin et al developed a non-invasive method for removing biofilms, which combines the acoustic cavitation effect induced by ultrasound and microbubbles with antibacterial compounds. 203 They used a dual emulsion method to encapsulate the convertible perfluoropentane and antibiotic meropenem in poly(lactic acid- co -glycolic acid) (PLGA) NPs, and then chemically coupled them to Pseudomonas aeruginosa specific monoclonal antibodies. Targeted delivery of antibiotic meropenem improved the antimicrobial efficacy and reduced the risk of antimicrobial resistance due to off-target effects.…”

Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?

“…Starting at a baseline bioluminescent intensity of 100%, the antibody-nanoparticle conjugate treatment was able to reduce bioluminescence to a mere 5% compared to saline (which saw an increase in bioluminescence to 150%) and free rifampicin (which saw a reduction in bioluminescence to 25%) [ 34 ]. Furthermore, Xin et al [ 132 ] have examined the wound healing activity of an ultrasound-activated, antibody-conjugated, perfluoropentane- and meropenem-loaded nanoparticle treatment against P. aeruginosa biofilm. The group used a 3D confocal laser scanning microscopy in combination with live/dead staining to qualify the bactericidal effect of treatment, reporting a significant amount of bacterial death in the sonication/nanoparticle group compared to the control, which had maintained high levels of bacteria embedded in biofilm.…”

Ultrasound-Based Micro-/Nanosystems for Biomedical Applications

“…Xin et al developed a robust antimicrobial strategy to effectively eradicate P. aeruginosa biofilms through the design of ultrasound-activatable targeted nanoparticles, which consisted of PLGA-encapsulated phase-transformable PFP and meropenem. 214 Under ultrasound exposure, PFP can be stimulated to generate microbubbles, thereby inducing ultrasonic cavitation effects. These effects have the potential to disrupt extracellular polymeric substance components, enabling the release of meropenem from nanoparticles for direct killing of P. aeruginosa and accelerated wound healing.…”

“…Xin et al developed a robust antimicrobial strategy to effectively eradicate P. aeruginosa biofilms through the design of ultrasound-activatable targeted nanoparticles, which consisted of PLGA-encapsulated phase-transformable PFP and meropenem . Under ultrasound exposure, PFP can be stimulated to generate microbubbles, thereby inducing ultrasonic cavitation effects.…”

“…(h) Schematic illustration of ultrasound-activatable phase-shift nanoparticles as a targeted antibacterial agent for efficient eradication of P. aeruginosa biofilms. Reprinted with permission from ref . Copyright 2022 American Chemical Society.…”