Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy

Ying-Chi Chen, Li-Chan Chang, Yan-Ling Liu, Ming-Che Chang, Yin-Fen Liu, Po-Ya Chang, Divinah Manoharan, Wen-Jyun Wang, Jia-Sin Chen, Hsueh-Chun Wang, Wen-Tai Chiu (), Wei-Peng Li (), Hwo-Shuenn Sheu (), Wen-Pin Su () and Chen-Sheng Yeh ()
Additional contact information
Ying-Chi Chen: National Cheng Kung University
Li-Chan Chang: National Cheng Kung University
Yan-Ling Liu: National Cheng Kung University
Ming-Che Chang: National Cheng Kung University
Yin-Fen Liu: National Cheng Kung University
Po-Ya Chang: National Synchrotron Radiation Research Center
Divinah Manoharan: National Cheng Kung University
Wen-Jyun Wang: Kaohsiung Medical University
Jia-Sin Chen: Kaohsiung Medical University
Hsueh-Chun Wang: National Cheng Kung University
Wen-Tai Chiu: National Cheng Kung University
Wei-Peng Li: Kaohsiung Medical University
Hwo-Shuenn Sheu: National Synchrotron Radiation Research Center
Wen-Pin Su: National Cheng Kung University
Chen-Sheng Yeh: National Cheng Kung University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-58636-2

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