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

Abstract

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 <i>Staphylococcus aureus</i> 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.