Targeted Cancer Therapy with Gold–Iron Oxide Nanourchins: Inducing Oxidative Stress, Paraptosis, and Sensitizing Tumor Cells to Cisplatin

Nanotechnology has revolutionized cancer therapy by enabling targeted drug delivery and overcoming limitations associated with conventional chemotherapy. In this study, we explored the anticancer potential of gold–iron oxide (Au-Fe3O4@PEG) nanourchins (NUs), a class of nanoparticles with unique shape, surface features, and plasmonic properties. We tested NUs on several cancer cell lines, including A375 (melanoma), MCF7 (breast), A549 (lung), and MIA PaCa-2 (pancreatic), and observed significant dose-dependent cytotoxicity, with A549 cells exhibiting the highest resistance. Our findings also demonstrate that NUs induce oxidative stress, disrupt mitochondrial function, and activate autophagic and paraptotic cell death pathways in A549 lung cancer cells. Additionally, we explored the potential of NUs to enhance the efficacy of platinum-based chemotherapy, specifically cisplatin, in A549. The results provide valuable insights into the therapeutic potential of NUs in the context of cancer treatment, particularly for overcoming drug resistance and enhancing the effectiveness of conventional chemotherapy.