@article{Lu2025, 
author = {Liang Lu and Songyirui Qiu and Wen Li and Hongbin Gong and Qi Zhang and Lihui Yuwen and Dongliang Yang and Zhaowei Yin and Lianhui Wang},
title = {Ultrasound-responsive multifunctional nanodroplets for enhanced biofilm penetration and synergistic sonodynamic/gas therapy of bacterial implant infections},
year = {2025},
journal = {Nano Research},
volume = {18},
number = {12},
pages = {94908166},
keywords = {ultrasound, sonodynamic therapy, nitric oxide, bacterial biofilm infection, phase-change nanodroplets},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94908166},
doi = {10.26599/NR.2025.94908166},
abstract = {Conventional antibiotic treatment of bacterial infections associated with biofilms usually suffers from poor penetration and drug resistance. Ultrasound (US)-responsive antibacterial systems have shown great promise in the elimination of bacterial biofilms, benefiting from their unique sonophysical and sonochemical effects. In this study, PFP@Lip-BNN6/Ce6 nanodroplets (PLBC NDs) were prepared by using perfluoropentane (PFP) to load chlorin e6 (Ce6) and a nitric oxide (NO) precursor (BNN6) for treating Staphylococcus aureus (S. aureus) implant infection. PLBC NDs physically disrupt the biofilm structure by US-triggered PFP phase transition and cavitation to enhance the permeation of Ce6 and BNN6. Under US irradiation, Ce6 generates various reactive oxygen species (ROS), such as singlet oxygen (1O2) and superoxide anion (O2•−); BNN6 releases NO and then reacts with O2•− to form peroxynitrite anion (ONOO−), one of the long-lived reactive nitrogen species (RNS), thus realizing synergistic ROS/RNS antibacterial activity. In vitro experiments showed that PLBC NDs reduced the biofilm biomass of S. aureus in 96-well plates by 65.9%, with a bacterial inactivation rate of 4.4 log (99.995%), significantly surpassing single treatments. Transcriptomic analysis indicated that PLBC NDs can interfere with key pathways of S. aureus biosynthesis, metabolism, and oxidative stress. In a mouse titanium implant infection model, PLBC NDs reduced the number of viable bacteria in infected tissues by 3.5 log (99.97%) and promoted macrophage polarization towards an anti-inflammatory phenotype (M2). Toxicity assessments demonstrated the favorable safety profile of PLBC NDs. This study presents a multifunctional US-responsive nanoplatform integrating sonophysical disruption and sonochemical killing for effective biofilm infection treatment.}
}