Ultrasound-responsive multifunctional nanodroplets for enhanced biofilm penetration and synergistic sonodynamic/gas therapy of bacterial implant infections

作者：Lu Liang, Songyirui Qiu, Li Wen, Hongbin Gong, Qi Zhang, Lihui Yuwen, Dongliang Yang, Zhaowei Yinc, Lianhui Wang · 发表于：Nano Research · 年份：2025 · DOI：10.26599/nr.2025.94908166 · 被引用次数：5 · 研究领域：Ultrasound and Hyperthermia Applications、Electrospun Nanofibers in Biomedical Applications、Ultrasound and Cavitation Phenomena

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 ( 1 O 2 ) and superoxide anion (O 2 .− ); BNN6 releases NO and then reacts with O 2 .− 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...