Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy

Cancer remains a global health challenge necessitating innovative therapies. We introduce a strategy to disrupt cancer cell redox balance using gold nanoparticles (Au NPs) as electron sinks combined with electroactive membranes. Utilizing Shewanella oneidensis MR-1 membrane proteins, we develop liposomes enriched with c-type cytochromes. These, coupled with Au NPs, facilitate autonomous electron transfer from cancer cells, disrupting redox processes and inducing cell death. Effective across various cancer types, larger Au NPs show enhanced efficacy, especially under hypoxic conditions. Oxidative stress from Au@MIL (MIL: membrane-integrated liposome) treatments, including mitochondrial and endoplasmic reticulum lipid oxidation and mitochondrial membrane potential changes, triggers apoptosis, bypassing iron-mediated pathways. Surface plasmon band and X-ray absorption near-edge structure (XANES) analyses confirm electron transfer. A SiO₂ insulator coating on Au NPs blocks this transfer, suppressing cancer cell damage. This approach highlights the potential of modulated electron transfer pathways in targeted cancer therapy, offering refined and effective treatments.