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 ironmediated 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. Human Hep G2 hepatocellular carcinoma cells (H) and human MDA-MB-231 triple-negative breast cancer cells (M) were treated with 300 ppm Au@MIL nanoparticles (MIL: Shewanella oneidensis MR-1 membrane-integrated liposome) for 24 hours. The treated groups were labeled as H_N and M_N, while untreated control groups were labeled as H_C and M_C. Total RNA was extracted from experimental cells using Trizol Reagent (#15596026, Thermo Fisher Scientific). For RNA library preparation, the refined RNA was processed with the TruSeq Stranded mRNA Library Prep Kit (Illumina, San Diego, CA, USA) according to the manufacturer's guidelines.