Green algae-derived sulfated polysaccharide-capped AgNPs with Decanoic and 9-Octadecenoic acid derivatives induce cytotoxicity via PI3Kα/mTOR pathway in HepG2 cell line.

The present study was explored with specific objectives of to synthesize silver nanoparticles (AgNPs) using Caulerpa racemosa sulfated polysaccharides and to evaluate their antioxidant properties, and anticancer efficacy against HepG2 liver cancer cell and molecular docking interactions with key cancer targets (PI3Kα and mTOR). AgNPs were synthesized via a green reduction method, confirmed by the color change from yellow to brown. It was characterized by UV-vis spectroscopy, FT-IR, XRD, SEM, DLS, and LC-MS analysis. UV-vis absorption peak at 430 nm showed Cr-AgNPs confirmation. FT-IR analysis confirmed the presence of hydroxyl (-OH) (3420 cm-1) with carbonyl (C=O), and amide (-CONH₂) groups. Specifically, the band at 1632.00 cm-1 attributed to CO stretching vibrations of conjugated ketones/ amide linkages. XRD patterns showed the crystalline structure as face-centered cubic and SEM and DLS analyses shown the spHerical morphology of Cr-AgNPs with moderate size distribution of 164.4 nm in dm. Furthermore, LC-MS identified key bioactive compounds such as sulphonamides, fatty acid esters and heterocyclic derivatives. The antioxidant potential of C. racemosa extract was assessed through DPPH, hydroxyl radical, reducing power, superoxide radical, and ABTS assays, which revealed a concentration-dependent increase in free radical scavenging. The extract exhibited IC₅₀ values of 72.1 μg mL-1 (DPPH) and 87.3 μg mL-1 (hydroxyl radical). In-silico docking showed strong binding affinities of decanoic acid and 9-octadecenoic acid (Z)-, methyl ester to PI3Kα and mTOR proteins with binding affinities of -8.0 and - 8.7 kcal/mol, respectively. 9-octadecenoic acid (Z) is a monounsaturated fatty acid with the structure CH₃(CH₂)₇CH=CH(CH₂)₇COOH, commonly known as oleic acid. Cytotoxicity was evaluated against HepG2 cells lines using an MTT assay, with an IC₅₀ of 18.3 ± 0.13 μg mL-1. This integrated approach combining LC-MS-guided compound profiling with in-silico docking represents a novel strategy in green nanomedicine. These findings support the development of seaweed-mediated nanotherapeutics, warranting further in-vivo studies to assess their clinical applications.