808 nm Light-Triggered Cyanine-Decorated Iridium(III) Complexes for Antibacterial Photodynamic Therapy in Deep-Tissue

Acute bacterial skin and skin structure infections (ABSSSIs) pose significant global health challenges, exacerbated by rising antibiotic resistance. Antibacterial photodynamic therapy (APDT) has emerged as a promising strategy to combat these infections by utilizing a photosensitizer (PS) that generates reactive oxygen species (ROS) upon light activation. However, the limited tissue penetration of conventional organic PSs, which primarily absorb in the UV-vis spectra, has hindered their therapeutic potential for deeper infections. Herein, we introduce a novel iridium(III)-cyanine complex (Ir-cy) with strong near-infrared (NIR) absorption at 814 nm (up to 101 nm red-shifted from previous reports), specifically designed to enhance tissue penetration for APDT. Under 808 nm laser irradiation, Ir-cy demonstrated a substantial ROS generation capacity, achieving approximately 70% reduction in Staphylococcus aureus (S. aureus) colonies at a depth of 7.2 mm within a simulated tissue model. Comprehensive in vitro and in vivo evaluations further confirmed its potent antibacterial efficacy against S. aureus while maintaining excellent biocompatibility. These findings highlight the potential of Ir-cy as a highly effective NIR-active PS, paving the way for advanced therapeutic strategies targeting deep-tissue ABSSSIs through optimized APDT.