To develop and evaluate a quercetin-loaded silicon dioxide–graphene nanocomposite (Que@SiO₂-GNPs) for targeted macrophage modulation and epithelial protection in a Mycoplasma-induced pneumonia model. Que@SiO₂-GNPs were synthesized via graphene oxide dispersion, sol–gel silica coating, and quercetin adsorption. Physicochemical properties were characterized by XPS, XRD, and FTIR. The therapeutic efficacy was evaluated in MP-infected rat models via histopathology, ELISA, flow cytometry, immunostaining, and Western blot. Cellular uptake, polarization, and functional assays were performed in primary AMs and BEAS-2B epithelial cells. Que@SiO₂-GNPs exhibited successful surface modification and quercetin incorporation with stable physicochemical properties. In vivo imaging demonstrated pulmonary targeting and favorable biocompatibility. In MP-infected rats, Que@SiO₂-GNPs significantly reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), alleviated lung injury, and promoted tissue repair. Mechanistically, the nanocomposites downregulated iNOS and CD86 while enhancing CD206 expression in AMs, indicating M2 polarization. Conditioned AMs improved epithelial proliferation, reduced oxidative stress and apoptosis, and upregulated SPLUNC1 expression. These outcomes were validated by EdU, ROS, Annexin V/PI, LDH assays, and protein expression analyses. Que@SiO₂-GNPs effectively reprogrammed macrophage phenotypes toward M2, suppressed inflammation, and conferred epithelial protection in Mycoplasma-induced pneumonia. This nanoplatform represents a promising immunomodulatory strategy for pulmonary infectious diseases. Not applicable.
Liu et al. (2026) studied this question.