Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy

Nat Commun. 2025 Apr 5;16(1):3253. doi: 10.1038/s41467-025-58636-2.

Ying-Chi Chen ^# ¹, Li-Chan Chang ^# ², Yan-Ling Liu ^# ¹, Ming-Che Chang ¹, Yin-Fen Liu ², Po-Ya Chang ³, Divinah Manoharan ¹, Wen-Jyun Wang ⁴, Jia-Sin Chen ⁴, Hsueh-Chun Wang ⁵, Wen-Tai Chiu ⁶, Wei-Peng Li ⁷ ⁸ ⁹ ¹⁰, Hwo-Shuenn Sheu ¹¹, Wen-Pin Su ¹² ¹³ ¹⁴ ¹⁵, Chen-Sheng Yeh ¹⁶ ¹⁷

Affiliations

1 Department of Chemistry, National Cheng Kung University, Tainan, 701, Taiwan.
2 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan.
3 National Synchrotron Radiation Research Center, Hsinchu, 30076, Taiwan.
4 Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
5 Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan.
6 Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan. wtchiu@mail.ncku.edu.tw.
7 Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. wpli@kmu.edu.tw.
8 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan. wpli@kmu.edu.tw.
9 Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. wpli@kmu.edu.tw.
10 Center of Applied Nanomedicine, National Cheng Kung University, Tainan, 701, Taiwan. wpli@kmu.edu.tw.
11 National Synchrotron Radiation Research Center, Hsinchu, 30076, Taiwan. hsheu@nsrrc.org.tw.
12 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan. wpsu@mail.ncku.edu.tw.
13 Center of Applied Nanomedicine, National Cheng Kung University, Tainan, 701, Taiwan. wpsu@mail.ncku.edu.tw.
14 Departments of Oncology and Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan. wpsu@mail.ncku.edu.tw.
15 Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan. wpsu@mail.ncku.edu.tw.
16 Department of Chemistry, National Cheng Kung University, Tainan, 701, Taiwan. csyeh@mail.ncku.edu.tw.
17 Center of Applied Nanomedicine, National Cheng Kung University, Tainan, 701, Taiwan. csyeh@mail.ncku.edu.tw.
# Contributed equally.

PMID: 40188189 DOI: 10.1038/s41467-025-58636-2

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.

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HY-K0601

JC-1 Mitochondrial Membrane Potential Assay Kit

Cell Apoptosis and Necrosis

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