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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 (mSiO2, 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@mSiO2-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.
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