Gold Nanoparticles Enhance the Antioxidant and Anticancer Properties of Fucoidan from Turbinaria decurrens and Sargas-sum cinereum: In Silico and In Vitro Insights

Background: Cancer remains one of the leading causes of mortality worldwide, while natural antioxidants have emerged as promising therapeutic agents in cancer treatment. Although fucoidan from brown algae shows anticancer potential, its efficacy is limited by bioavailability challenges, and the synergistic effects of combining it with gold nano-particles remain unexplored. Methods: Fucoidan was extracted from Sargassum cinereum and Turbinaria decurrens using acid precipitation. Gold nanoparticles (AuNPs) were manufactured by a green technique that employed fucoidan as both a reducing and stabilizing agent. The nanoparticles were analyzed utilizing UV-Vis spectroscopy, FTIR, TEM, XRD, and zeta potential assessment. Antioxidant activities were evaluated utilizing DPPH and FRAP assays. Cytotoxicity was assessed against HepG2, THP-1, and BNL cells utilizing MTT and SRB tests. Flow cytometry was utilized for cell cycle analysis, and molecular docking was applied to examine interactions with cancer-associated proteins. Results: T. decurrens yielded higher fucoidan extraction (235.9 mg/g dry weight) and demonstrated superior antioxidant activity in Ferric Reducing Antioxidant Power (FRAP) (9.21 μg Trolox Equivalents /mg) and 2, 2-Diphenyl-1-Picryl-Hydrazyl-Hydrate (DPPH) (4.48 μg Trolox Equivalents /mg) assays compared to S. cinereum. Molecular docking revealed strong binding of fucoidan to cancer-related proteins, particularly COX-2 (-7.1 kcal/mol) and TERT (-5.4 kcal/mol), while the fucoidan-gold nanoparticle complex (F-AuNPs) showed enhanced cellular uptake and improved cytotoxicity against HepG2 cells (IC50: 392.81 μg/mL and 459.75 μg/mL for S. cinereum and T. decurrens formulations, respectively). Conclusions: These findings suggest a promising synergistic approach for enhancing fucoidan-gold nanoparticle therapeutic potential in cancer treatment through combined in vitro and in silico analyses.