Nanoparticle-Based Delivery of Resveratrol Suppresses Ehrlich Ascites Carcinoma and Protects Testicular Function via Antioxidant, Anti-Angiogenic, Anti-Inflammatory, and Pro-Apoptotic Mechanisms

This study, for the first time, evaluated the therapeutic potential of resveratrol-loaded phytosome nanoparticles (RES-PNPs) against Ehrlich ascites carcinoma (EAC) and associated testicular dysfunction, compared with free resveratrol (RES). Ninety male Swiss albino mice were divided into six groups, (1) control; (2) RES (10 mg/kg/day, orally); (3) RES-PNPs (10 mg/kg/day, orally); (4) EAC, induced by intraperitoneal injection of 2.5 × 10⁶ cells; (5) EAC + RES; and (6) EAC + RES-PNPs, treated for 20 days post-tumor inoculation. Tumor growth parameters, reproductive function, antioxidant enzyme activities, inflammatory mediators, apoptotic markers, and histopathological features were assessed. Additionally, in silico docking was performed to identify molecular targets mediating RES effects. RES-PNPs markedly reduced tumor volume, ascitic cell viability, and body weight gain while significantly prolonging survival compared with free RES. Molecular assays revealed enhanced pro-apoptotic signaling (increased Bax and Caspase-3, decreased Bcl-2), suppression of vascular endothelial growth factor (VEGF), and inhibition of COX-2 with reduced TNF-α, IFN-γ, and IL-1β levels. RES-PNPs also restored semen quality, normalized reproductive hormones, elevated antioxidant enzyme activities, and reduced lipid and protein oxidation, corroborated by notable testicular histological protection. In conclusion, Resveratrol-loaded phytosome nanoparticles provide superior anti-tumor, antioxidant, anti-inflammatory, and pro-apoptotic benefits compared with free RES. These findings highlight RES-PNPs as a potent and stable nanoformulation for effective EAC suppression and preservation of male reproductive integrity.