Lauramide-functionalized silver-selenide nanoparticles enhance the therapeutic efficacy of pyrimethamine in murine reactivated toxoplasmosis.

This study investigated the antiparasitic efficacy of lauramide-functionalized silver-selenide nanoparticles (Lu@AgSe NPs), alone or combined with pyrimethamine (PM), in a murine model of dexamethasone-induced reactivated toxoplasmosis. Reactivated toxoplasmosis was induced in chronically infected dexamethasone immunosuppressed BALB/c mice. Animals received Lu@AgSe NPs (5 or 10 mg/kg), PM, or combination therapy for 14 days. Parasite burden, oxidative stress biomarkers, inflammatory mediators, apoptosis-related genes, and hepatic and renal biochemical parameters were evaluated using qPCR and standard biochemical assays. Lu@AgSe NPs were observed to be spherical with a size range of 30-55 nm. Treatment significantly reduced parasite burden and improved survival in a dose-dependent manner (p < 0.001). Combination therapy with Lu@AgSe NPs (5 and 10 mg/kg) and low-dose PM (5 mg/kg) produced the most pronounced effects, including restoration of antioxidant enzyme activities (p < 0.001), reduction of lipid peroxidation (p < 0.001), modulation of inflammatory and apoptosis-related gene expression (p < 0.001), and improvement of hepatic and renal biochemical markers (p < 0.001). These findings indicate that combination therapy produced significantly greater therapeutic benefits than either agent administered alone, supporting the potential of Lu@AgSe NPs as an adjunctive treatment strategy. Lu@AgSe NPs demonstrated potential adjunctive therapeutic activity against reactivated toxoplasmosis, particularly when combined with low-dose PM. Their effects were associated with reduced parasite burden, modulation of oxidative stress, and regulation of immune- and apoptosis-related responses. Further mechanistic and toxicological investigations are warranted.