Selenium nanoparticle-enhanced resveratrol suppresses pulmonary inflammation and fibrogenesis in silicosis via redox-mediated inflammatory pathway modulation.

Silicosis, an occupational lung illness linked to the inhalation of silica (Si) particles, is marked by enduring oxidative stress, chronic inflammation, and advancing pulmonary fibrosis. This work conducted a comparative assessment of the therapeutic efficacy of resveratrol (RES)-loaded solid lipid nanoparticles (RNP) against RES-mediated green-synthesized selenium (Se) nanoparticles (SNP) in a mouse model of silicosis. Intratracheal Si instillation resulted in considerable pulmonary injury, characterized by increased hydroxyproline, oxidative stress (elevated MDA along with reduced GSH, SOD, and CAT), and the activation of inflammatory (TLR4/NF-κB/NLRP3/IL-1β/IL-6) and fibrogenic (TGF-β/Smad) responses. Although free RES and Se moderately attenuated these alterations, their nanoformulations exerted a potent protective efficacy. SNP significantly surpassed RNP, nearly restoring antioxidant capacity and markedly inhibiting inflammatory and fibrotic cascades. Histopathological and immunohistochemical evaluations demonstrated that nano-treatments, particularly SNP, significantly decreased collagen deposition, α-SMA expression, and inflammatory infiltrates, while reinstating SIRT1 levels. Multivariate analyses (PCA, clustering heatmaps) further confirmed that SNP therapy clustered close to the controls, attesting the mitigating potential against Si-evoked damage. The increased effectiveness of nanoformulations was due to greater bioavailability, prolonged release, and precise distribution. This study identifies RES-synthesized SNP as an effective nanotherapeutic approach for silicosis, operating through the concurrent modulation of the inflammatory and fibrotic signaling, mainly by restoring redox homeostasis.