Thermophilic bio-factory Bacillus sonorensis SS1 for superparamagnetic iron sulfide nanoparticles (FeSNPs) synthesis: in vitro and molecular modeling studies of anticancer activity

An eco-friendly method lets the thermophilic Bacillus sonorensis SS1 synthesize superparamagnetic nano-sized iron sulfide particles (FeSNPs) as bio-factories. These clean and non-toxic FeSNPs have led to increased interest in using inorganic nanoparticles (NPs) in health materials and industrial products. The biosynthesized FeSNPs exhibited an average particle size of approximately 4.5 nm and a negative surface charge (- 16.8 ± 0.6 mV), indicating good colloidal stability. In vitro cytotoxicity evaluation using the MTT assay demonstrated concentration-dependent growth inhibition against five cancer cell lines (A549, HeLa, MCF-7, HepG2, and HCT-116), with IC₅₀ values ranging from 18 to > 100 µg/mL. The highest cytotoxic activity was observed against A549 (IC₅₀ = 18 µg/mL) and HeLa (IC₅₀ = 27 µg/mL) cells, and MCF-7 (IC₅₀ = 75 µg/mL) showed moderate sensitivity, while comparatively lower sensitivity was detected in HepG2 and HCT-116 cells (IC₅₀ value > 100 µg/mL). In contrast, normal peripheral blood mononuclear cells (PBMCs) exhibited minimal cytotoxicity, with an IC₅₀ value > 100 µg/mL, indicating selective anticancer activity of the FeSNPs. The molecular docking studies demonstrated that the FeSNPs exhibit a strong binding affinity to the active sites of Caspase-3, VEGFR, and Aurora-A. These interactions suggest that FeSNPs can effectively inhibit critical pathways involved in tumor growth, angiogenesis, and radiotherapy resistance. The biochemical validation confirmed these interactions, showing a 14.6-fold induction of active Caspase-3 (516.8 ± 20.1 pg/mL) in A549 cells. Additionally, FeSNPs exhibited potent inhibitory activity against VEGFR2 (IC₅₀ = 0.447 ± 0.019 µg/mL) and Aurora-A (IC₅₀ = 0.268 ± 0.012 µg/mL). These findings demonstrate the potential of FeSNPs as multifunctional agents capable of simultaneously triggering apoptosis and disrupting angiogenic and proliferative pathways. The findings focus on the potential of FeSNPs as versatile therapeutic agents in cancer therapy.