Carvacrol combined with NIR light-responsive nano-drug delivery system with specific anti-bacteria, anti-inflammation, and immunomodulation for periodontitis

Bacterial infection, biofilm formation, and immune dysfunction are common triggers and aggravators in periodontitis, which render periodontal restoration challenging. Thus, a strategy with antibacterial, anti-inflammatory, and immunoregulatory capacities has great promise in the clinical practice of periodontitis. Herein, carvacrol (CA)-based near-infrared (NIR) light-responsive nano-drug delivery system is developed for the first time. The system consists of upconversion nanoparticles (UCNPs, which upconvert 808 nm NIR to blue light), mesoporous silica (mSiO 2 , the carrier channel), and hydrophobic CA (blue light response properties). Under the irradiation of 808 nm NIR, owing to the synergy of CA and upconverted blue light, the UCNPs@mSiO 2 -CA (UCMCs) exhibit the properties of specific anti-bacteria (including anaerobic bacteria), anti-inflammation, and immunomodulation. Notably, high-throughput sequencing results exhibit that many classic inflammatory immune-related signaling pathways, including the MAPK signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway, are enriched to remodel the immune microenvironment. Additionally, UCMCs with NIR irradiation accelerate periodontal restoration and serve as promising non-invasive management of periodontitis. Altogether, this study verifies the feasibility of herbal monomer combined with light-responsive in situ nano-drug delivery system and provides a more effective and reliable strategy for various potential applications of deep tissue diseases.