NIR-II triggered Cu(I) phosphide for chemodynamic and photothermal periodontitis treatment: efficient reduction of bacterial co-aggregation

Abstract

The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) offers a promising antimicrobial strategy for periodontitis, yet faces challenges like complex material structure and limited NIR-I light penetration. Additionally, low endogenous H2O2 levels in biofilm and a focus on bacterial eradication over colonization prevention limit current treatments. To address these issues, we newly introduce a single-material system (Cu3P@PAH@Lox) that integrates dual functionalities to synergistically enhance antimicrobial effects and significantly reduce pathogen co-aggregation. This system utilizes PTT to increase local temperature, boosting •OH production in CDT while downregulating heat shock proteins to enhance PTT efficacy, forming a self-reinforcing feedback loop. Lactate oxidase (Lox) is employed to convert lactate-a metabolite in periodontal biofilm-into H2O2, further amplifying CDT's potential. In vitro Cu3P@PAH@Lox demonstrates a remarkable synergistic effect against dual-species biofilms by more than 2-log reduction of colony-forming unit. Moreover, Cu3P@PAH@Lox exhibits outstanding synergistic antibacterial performances to alleviate inflammation and destruction of tissue in vivo periodontitis model. Furthermore, the mechanism of pathogen co-aggregation disruption by PTT is verified via the Cbe-Ltp1-Ptk1-fimA signaling pathway. This single-material multimodal system we have herein demonstrated for the first time marks a significant advancement in periodontitis treatment, eradicating microbes and preventing bacterial colonization, offering a path to comprehensive periodontal care. STATEMENT OF SIGNIFICANCE: The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) has been considered a promising therapy for periodontitis. Yet, facing challenges, the complex material structure, limited NIR-I light penetration, low endogenous H2O2 level in biofilm, and a focus on bacterial eradication over colonization prevention are still insufficient. This study pioneers a unique, single-material system (Cu3P@PAH@Lox) that synergistically enhances antimicrobial effects and substantially curtails pathogen co-aggregation, advancing periodontitis therapy. By exploiting PTT to elevate local temperatures, thereby increasing hydroxyl radical production in CDT and concurrently suppressing heat shock proteins, the system establishes a potent, self-enhancing loop. Furthermore, lactate oxidase is innovatively utilized to convert lactate from periodontal biofilm into hydrogen peroxide, augmenting the efficacy of CDT. The introduction of Cu3P@PAH@Lox is poised to revolutionize periodontitis treatment, eliminating microbes and impeding bacterial colonization, thereby charting a course for comprehensive periodontal management.