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.

Hydrogen peroxide (H₂O₂), as a signaling molecule, plays a vital role in a wide variety of signaling transduction processes, aging, and diseases. However, the excessive production of H₂O₂ causes various diseases. Herein, we develop a novel method for H₂O₂ detection in live cells via dark-field scattering spectroscopy with gold triangular nanoprisms (AuTNPs) as probes. The corners of AuTNPs would be gradually oxidatively etched by the strong coordination of Br^• which is generated by enzymatic reactions in the presence of horseradish peroxidase (HRP), bromide ion and trace hydrogen peroxide. Benefitting from the morphological change, the single AuTNP based plasmonic nanoprobe shows notable blueshifts and scattering color changes which could be real-time monitored under the dark-field microscopy. The peak position in the scattering spectra of individual AuTNP blueshifts linearly with the increase of H₂O₂ concentration, and exhibits high sensitivity to H₂O₂ in a large range from 2.5 to 100 μM with a low detection limit (LOD) of 0.74 μM. Moreover, the experimental results were supported by the simulated results via the finite-difference time-domain (FDTD) method. The nanoprobes have been further used for intracellular H₂O₂ detection in live cells. Besides, the etching of AuTNP also provides an alternative method to design novel plasmonic logic chips and write-once plasmonic memories.