ZIF-8-based Schottky heterojunction for boosting the sonodynamic antimicrobial effect of chlorin e6 on MRSA

Sonodynamic antimicrobial chemotherapy (SACT) has been regarded as an emerging approach for antimicrobial treatment due to its advantages of deep tissue penetration, non-invasive nature, and absence of resistance. However, several challenges hinder its clinical application, for example insufficient oxygen levels at infection sites, poor solubility and stability of sonosensitizers. Herein, we developed chlorin e6@ZIF-8@Ag (CZ@Ag) nanocomposite as a Schottky heterojunction sonosensitizer with high electron-hole separation and narrow bandgap. The results reveal that the Schottky barrier between ZIF-8 and Ag nanoparticles can availably restrain electron backflow, further promoting the yield of reactive oxygen species (ROS) under ultrasound treatment. Experimentally, the minimum inhibitory concentration of CZ@Ag against methicillin-resistant Staphylococcus aureus (MRSA) reduced from 320 μg/mL to 80 μg/mL, and its antibacterial rate was up to 96.3 % after 3 min of ultrasound irradiation. Furthermore, mechanistic studies found that CZ@Ag-mediated SACT is mainly achieved by inhibiting biofilm formation, damaging cell membrane integrity, enhancing more ROS generation, and increasing cell membrane permeability, leading to the leakage of intracellular contents. All these findings proved that CZ@Ag had great possibility for antibacterial therapy, and this investigation offered a feasible direction for developing efficient sonosensitizers.