N‐Acetyl‐l‐cysteine‐Derived Carbonized Polymer Dots with ROS Scavenging via Keap1‐Nrf2 Pathway Regulate Alveolar Bone Homeostasis in Periodontitis

Abstract

Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption. As oxidative stress is the key cause of periodontitis in the early periodontal microenvironment, antioxidative therapy has been considered a viable treatment for periodontitis. However, more stable and effective reactive oxygen species (ROS)‐scavenging nanomedicines are still highly needed due to the instability of traditional antioxidants. Herein, a new type of N‐acetyl‐l‐cysteine (NAC)‐derived red fluorescent carbonized polymer dots (CPDs) has been synthesized with excellent biocompatibility, which can serve as an extracellular antioxidant to scavenge ROS effectively. Moreover, NAC‐CPDs can promote osteogenic differentiation in human periodontal ligament cells (hPDLCs) under H2O2 stimulation. In addition, NAC‐CPDs are capable of targeted accumulation in alveolar bone in vivo, reducing the level of alveolar bone resorption in periodontitis mice, as well as performing fluorescence imaging in vitro and in vivo. In terms of mechanism, NAC‐CPDs may regulate redox homeostasis and promote bone formation in the periodontitis microenvironment by modulating the kelch‐like ECH‐associated protein l (Keap1)/nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway. This study provides a new strategy for the application of CPDs theranostic nanoplatform for periodontitis.

Melatonin-Derived Carbon Dots with Free Radical Scavenging Property for Effective Periodontitis Treatment via the Nrf2/HO-1 Pathway

“…Furthermore, our previous investigation showed Metronidazole-derived carbon dots featuring selective antibacterial activity and fluorescent properties, essential for periodontal disease treatment, offering prospects for addressing other bacterial-driven diseases . In our recent research, carbonized polymer dots derived from N -acetyl- l -cysteine were found to exhibit mitochondrial colocalization and a specific enrichment in periodontal tissues, facilitating the exertion of their antioxidant therapeutic effects . These studies collectively underscore the advantages and potential of carbon dots for the therapy of periodontitis.…”

“…38 In our recent research, carbonized polymer dots derived from Nacetyl-L-cysteine were found to exhibit mitochondrial colocalization and a specific enrichment in periodontal tissues, facilitating the exertion of their antioxidant therapeutic effects. 39 These studies collectively underscore the advantages and potential of carbon dots for the therapy of periodontitis.…”

Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment

“…These techniques are capable of introducing cationic segments, such as N,N ′-dimethylamino-2-ethyl methacrylate (DMAEMA), 2-( tert -butylamino)ethyl methacrylate, and amino butyl methacrylate, into the polymer backbone to realize antibacterial activities. 170 Takahashi synthesized a cationic methacrylate copolymer with amino butyl methacrylate as the antibacterial segment (Fig. 10a).…”

“…23). 170 Cysteine is a widely used antioxidant. By constructing NAC-CPDs through formamide-assisted solvothermal reaction, the stability of NAC was greatly improved than when it was encapsulated into carriers.…”

Role of oxidative stress in the relationship between periodontitis and systemic diseases

“…LPS can stimulate the generation of proinflammatory cytokines, which provoke and sustain immune cell recruitment and activation as well as tissue damage in periodontal tissues ( Han et al, 2022 ). Concurrently, oxidative stress causes direct harm to cells and tissues, leading to further tissue damage, as well as inflammatory responses that increase the microbial dysbiosis ( Liu et al, 2023 ). Cumulatively, the shift towards an anaerobic Gram-negative bacterial community, along with the presence of LPS and oxidative stress, act synergistically to promote chronic inflammation and to foster the exacerbation of periodontal diseases ( Willmann et al, 2018 ).…”