Synergistic Photothermal and Photodynamic Therapy for Effective Implant-Related Bacterial Infection Elimination and Biofilm Disruption Using Cu9S8 Nanoparticles

Implant-related bacterial infections are one of the most common but tricky problems in orthopedic clinics because the formation of biofilms inhibits the penetration of antibiotics to kill bacteria effectively; thus, a new strategy is urgently needed. Antibacterial nanomaterials [e.g., copper (Cu)-based nanoparticles (NPs)] combined with near-infrared (NIR) irradiation show enhanced antibacterial activity against clinical bacteria. However, their antibacterial efficiency toward implant-related infections and against biofilm formation remains unclear. Here, unique polyethylene glycol-modified Cu₉S₈ NPs with good biocompatibility were synthesized. We found that the Cu₉S₈ NPs exhibited high photothermal performance and could increase the generation of reactive oxygen species under NIR irradiation (808 nm, 1 W cm^-2). The Cu₉S₈ NPs with NIR irradiation successfully destroyed the bacterial structure, resulting in the death of the clinically derived Staphylococcus aureus growing on titanium (Ti) plates. Moreover, this excellent antibacterial activity was indicated to have a synergistic effect with photothermal therapy (PTT) and photodynamic therapy (PDT) by comparison to Cu₉S₈ with heating treatment in a water bath with similar temperature changes compared to NIR + Cu₉S₈. Finally, the biofilm formation on the Ti plates was effectively disrupted by NIR + Cu₉S₈ treatment, while Cu₉S₈ with thermal treatment showed a mild impact. Hence, Cu₉S₈ NP-based PTT and PDT can provide a promising approach to eliminating implant-related bacteria and disrupting bacterial biofilms.