Crocus sativus L.-derived lauric acid-functionalized gold nanoparticles induce ferroptosis in HeLa cells and reverse M2 macrophage polarization via the PGE2/EP2/cAMP-PKA signaling pathway: a network pharmacology-based study

Introduction Cervical cancer ranks as the fourth most common malignancy among women worldwide. It is closely associated with the dysregulation of numerous genes and signaling pathways. Conventional treatments for cervical cancer often lead to adverse side effects and the development of drug resistance. Methods In this study, network pharmacology was employed to identify the active components and potential targets of Crocus sativus L. Molecular docking and surface plasmon resonance analyses were used to validate the interaction between lauric acid and a key target. Lauric acid‐modified gold nanoparticles (Au@LA) were synthesized and characterized. Results Twenty‐three active components and 819 potential targets of Crocus sativus L. were identified, with PTGS2 being the main target. Au@LA selectively inhibited HeLa cell proliferation, induced apoptosis, downregulated SLC7A11 and GPX4, and modulated oxidative stress markers. In macrophages, Au@LA shifted M2 polarization to the pro‐inflammatory M1 phenotype and modulated the PGE2/EP2/cAMP‐PKA signaling axis. Conclusion Our findings indicate that Au@LA has dual anti‐cervical cancer properties through inducing ferroptosis in HeLa cells and reprogramming macrophage polarization. It shows promise as a candidate for natural product‐based nanomedicine in cervical cancer therapy, potentially opening new avenues for more effective and targeted treatments in the future.