biostudies-literatureChoi VEngineering and Physical Sciences Research Council22https://www.ebi.ac.uk/biostudies/studies/S-EPMC11962098biostudies-literatureUnknown3(1)Chronic infections represent a major clinical challenge due to the enhanced antimicrobial tolerance of biofilm-dwelling bacteria. To address this challenge, an ultrasound-responsive nanoscale drug delivery platform (nanodroplets) is presented in this work, loaded with four different antimicrobial agents, capable of simultaneous biofilm disruption and targeted antimicrobial delivery. When loaded, a robust protective effect against clinically-derived MRSA and ESBL Gram-positive and Gram-negative planktonic isolates was shown in vitro. Upon application of therapeutic ultrasound, an average 7.6-fold, 44.4-fold, and 25.5-fold reduction was observed in the antibiotic concentrations compared to free drug required to reach the MBC, MBEC and complete persister eradication levels, respectively. Nanonpj antimicrobials and resistanceRepurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery.PMC11962098EP/V026623/1Choi VCarugo DStride EfalseRepurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery.Chronic infections represent a major clinical challenge due to the enhanced antimicrobial tolerance of biofilm-dwelling bacteria. To address this challenge, an ultrasound-responsive nanoscale drug delivery platform (nanodroplets) is presented in this work, loaded with four different antimicrobial agents, capable of simultaneous biofilm disruption and targeted antimicrobial delivery. When loaded, a robust protective effect against clinically-derived MRSA and ESBL Gram-positive and Gram-negative planktonic isolates was shown in vitro. Upon application of therapeutic ultrasound, an average 7.6-fold, 44.4-fold, and 25.5-fold reduction was observed in the antibiotic concentrations compared to free drug required to reach the MBC, MBEC and complete persister eradication levels, respectively. Nano2025-01-01T00:00:00Z2025 Apr2026-07-15T14:39:24.349Z2025-06-28T03:05:21.795ZS-EPMC119620984016991510.1038/s44259-025-00086-3