Here, we report a general ultrasound-assisted photodynamic strategy that overcomes this challenge by employing hypocrellin B (HB), originally a narrow-spectrum agent initially effective against Gram-positive bacteria, to eradicate Gram-negative bacteria. By applying exogenous ultrasound (US), we induce interfacial electron movement and leverage the cavitation effect to disrupt the lipid bilayer structure of the outer membrane (OM). Consequently, 200 μg mL −1 of HB@ZIF-8 (ZHB) achieves an almost 7-log reduction in Escherichia coli counts wit...