Protease-Loaded CuS Nanoparticles with Synergistic Photothermal/Dynamic Therapy against F. nucleatum-Induced Periodontitis

ACS Appl Mater Interfaces. 2023 Jul 12;15(27):32215-32225. doi: 10.1021/acsami.3c04534. Epub 2023 Jun 26.

Abstract

Periodontitis is a chronic inflammatory disease induced by a plaque biofilm, which can lead to the destruction of the periodontal support tissue and even teeth loss. The common strategies of periodontitis treatment are to eliminate bacterial/biofilm-related inflammation and subsequently inhibit alveolar bone resorption, for which antibiotic therapy is the most traditional one. However, impenetrable polymeric substances on bacterial biofilms make it difficult for traditional antimicrobial agents to take effect. In this study, a novel nanoparticle protease-loaded CuS NPs was developed, combining the advances of photodynamic and photothermal therapy from CuS and enzymatic degradation of the biofilm by a protease. The photothermal activity and the reactive oxygen generation capacity of the designed nanoparticles were verified by the experimental results, constituting the basis of antibacterial function. Next, the high antimicrobial activity of CuS@A NPs onFusobacterium nucleatumand its biofilm was demonstrated. The proper hemo/cytocompatibility of CuS-based NPs was demonstrated by in vitro assays. Last, effective treatment against periodontitis was achieved in a rat periodontitis model through the significant efficacy of inhibiting bone resorption and alleviating inflammation. Thus, the developed CuS@A NPs prove a promising material for the management of periodontitis.

Keywords: Alcalase; CuS nanoparticles; antibiofilm; periodontitis; photodynamic therapy; photothermal therapy.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Copper / pharmacology
  • Copper / therapeutic use
  • Inflammation
  • Nanoparticles*
  • Peptide Hydrolases
  • Periodontitis* / drug therapy
  • Periodontitis* / microbiology
  • Photochemotherapy* / methods
  • Photothermal Therapy
  • Rats

Substances

  • Peptide Hydrolases
  • Anti-Bacterial Agents
  • Copper