Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy

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 dev...

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Main Authors: 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, Chen-Sheng Yeh
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58636-2
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author 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
Chen-Sheng Yeh
author_facet 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
Chen-Sheng Yeh
author_sort Ying-Chi Chen
collection DOAJ
description 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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spelling doaj-art-7fedcabcd9e84f70bf2df7135b16edb72025-08-20T03:07:43ZengNature PortfolioNature Communications2041-17232025-04-0116111710.1038/s41467-025-58636-2Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapyYing-Chi Chen0Li-Chan Chang1Yan-Ling Liu2Ming-Che Chang3Yin-Fen Liu4Po-Ya Chang5Divinah Manoharan6Wen-Jyun Wang7Jia-Sin Chen8Hsueh-Chun Wang9Wen-Tai Chiu10Wei-Peng Li11Hwo-Shuenn Sheu12Wen-Pin Su13Chen-Sheng Yeh14Department of Chemistry, National Cheng Kung UniversityInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityDepartment of Chemistry, National Cheng Kung UniversityDepartment of Chemistry, National Cheng Kung UniversityInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityNational Synchrotron Radiation Research CenterDepartment of Chemistry, National Cheng Kung UniversityDepartment of Medicinal and Applied Chemistry, Kaohsiung Medical UniversityDepartment of Medicinal and Applied Chemistry, Kaohsiung Medical UniversityDepartment of Biomedical Engineering, National Cheng Kung UniversityDepartment of Biomedical Engineering, National Cheng Kung UniversityDepartment of Medicinal and Applied Chemistry, Kaohsiung Medical UniversityNational Synchrotron Radiation Research CenterInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityDepartment of Chemistry, National Cheng Kung UniversityAbstract 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.https://doi.org/10.1038/s41467-025-58636-2
spellingShingle 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
Chen-Sheng Yeh
Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
Nature Communications
title Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
title_full Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
title_fullStr Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
title_full_unstemmed Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
title_short Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
title_sort redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
url https://doi.org/10.1038/s41467-025-58636-2
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