Sustainable gold nanoparticles using Jania rubens, targeted therapeutic potential in prostate cancer and mechanistic insights via GO/KEGG pathway analysis
摘要
Gold nanoparticles (AuNPs) are highly versatile nanomaterials due to their exceptional physicochemical and biological properties with promising biomedical applications. This study presents a rapid, eco-friendly biosynthesis of AuNPs using the red alga Jania rubens (Jan-AuNPs). GC analysis of the algal extract revealed a total fatty acid content of 1.41 mg/g DW, dominated by saturated fatty acids primarily methyl palmitate (53.22%) and methyl stearate (27.89%) alongside methyl oleate (9.42%). Phytochemical profiling demonstrated a rich biochemical composition, including a high total phenolic content of 299.82 ± 1.83 mg GAE/g DW, total flavonoid content of 35.61 ± 0.52 mg QE/g DW, and total carbohydrate content (TCC) of 166 ± 1.05 mg GE/g DW, collectively conferring potent reducing, capping and stabilizing capacities of the algal extract in mediating Jan-AuNPs biosynthesis. Formation of Jan-AuNPs was visually confirmed by a color change from pale yellow to ruby red or pinkish-red, which was further confirmed by UV–vis spectroscopy with a surface plasmon resonance (SPR) peak at 549 nm. TEM analysis revealed predominantly spherical particles with an average diameter of 16.26 nm, with a few rod-shaped particles also detected. The crystalline nature of Jan-AuNPs was validated by XRD and SAED analyses. Zeta potential measurements revealed a surface charge of -28 mV, indicating good colloidal stability. FTIR analysis confirmed the active involvement of diverse algal biomolecules in the formation and stabilization of Jan-AuNPs. Biosynthesis conditions were optimized using face-centered central composite design (FCCCD), achieving the highest yield of 289 µg/mL at pH 7, 60 °C, 3 h incubation, and 300 µg/mL gold ion concentration. In silico predictive analysis identified cancer-associated gene targets modulated by AuNPs, thereby predicting prostate cancer (PC) as the malignancy with the highest therapeutic susceptibility for AuNPs-based interventions. Experimental validation confirmed potent and selective antitumor activity against PC3 prostate cancer cells in vitro (IC50 = 6.39 µg/mL; SI = 15.24) with minimal cytotoxicity toward normal HFB4 cells (IC50 = 97.41 µg/mL). In vivo evaluation using the Ehrlich ascites carcinoma (EAC) model in Swiss albino mice demonstrated that combined treatment with Jan-AuNPs and doxorubicin achieved a tumor growth inhibition of 97.33%. These findings establish Jania rubens-mediated biosynthesis as a sustainable and scalable platform for producing bioactive AuNPs and highlight the pivotal role of bioinformatics in guiding experimental cancer nanomedicine research. The results highlight Jan-AuNPs as a promising, safe, and multi-targeted nanotherapeutic candidate with significant potential for the management of prostate cancer.