Boron subphthalocyanine aggregates enable antimicrobial photodynamic therapy against antibiotic-resistant bacteria in nanomolar concentrations

Abstract

Antibiotic resistance continues to motivate non-antibiotic approaches for bacterial control. Antimicrobial photodynamic therapy (aPDT), which combines a photosensitizer, light, and oxygen to generate cytotoxic reactive oxygen species, offers a route to oxidative killing that is independent of conventional antibiotic targets. Boron subphthalocyanines (BsubPcs) possess suitable photophysical properties for PDT and structural tunability, yet their antimicrobial potential remains underexplored. Here, we evaluate how axial versus peripheral fluorination within a BsubPc scaffold impacts aqueous behavior, photoreactivity, and aPDT performance. Among the evaluated compounds, PhO-BsubPc achieved complete bacterial eradication (>6-log reduction) at 5 nM with 525 nm irradiation (10 J cm -2 ), while Rose Bengal showed no activity at 5 nM under the same conditions. Activity extended to methicillin-resistant S. aureus (MRSA), with PhO-BsubPc maintaining improved potency at low nanomolar concentrations. Overall, these results position BsubPcs as a compact, formulation-minimal platform for aPDT against drug-resistant bacteria.