Enhancing the Therapeutic Efficacy of silibinin via Silica-Coated magnetic Nanocomposite against Pseudomonas aeruginosa isolates and HepG2 cancer cells Running title: Potential therapeutic properties of silibinin

Introduction : Silibinin is a notable component extracted from Silybum marianum with antioxidant, antitumor, hepatoprotective, and antibacterial activities. This study aims to enhance the delivery of silibinin by synthesizing magnetic nanocomposites (MNCs) to address its poor solubility in clinical isolates of P. aeruginosa and HepG2 cancer cells. Methods : The physicochemical characterization of Fe ₃ O ₄ @SiPr@Silibinin nanocomposites was thoroughly measured via FT-IR, TGA-DTG, TEM, FE-SEM, XRD, and VSM. Clinical isolates and standard strain of P. aeruginosa were treated with Fe ₃ O ₄ @SiPr@Silibinin (sub-MIC) in combination with ciprofloxacin (sub-MIC) compared to treatment with sub-MIC of ciprofloxacin alone. Additionally, the anticancer effects of Fe ₃ O ₄ @SiPr@Silibinin were assessed on HepG2 cells. Results : The nanocomposites had particle sizes ranging from 40 to 80 nm and significantly enhanced the antimicrobial effects of ciprofloxacin when used in combination. The Fe ₃ O ₄ @SiPr@Silibinin + ciprofloxacin treatment resulted in decreased expression of biofilm and efflux pump genes compared to ciprofloxacin treatment alone. Fe ₃ O ₄ @SiPr@Silibinin (IC50=35.79 µg/mL) also demonstrated anti-cancer activity against HepG2 cells. In Silibinin treated HepG2 cells, overexpression of the P53 gene and under-expression of the Bcl2 gene were observed. Discussion : Our anulysis suggests that Fe ₃ O ₄ @SiPr@Silibinin MNCs, with high stablilty and high solublity in water, can more efficiently transfer silibinin into pathogenic and tumorigenic cells, thus increasing its therapeutic functions against P. aeruginosa and HepG2 cells. Given the antimicrobial and anti-tumor properties of silibinin, these magnetic nanocarriers may represent a novel strategy for its targeted delivery.