Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapy

Abstract Anaerobic bacteria-mediated tumor therapy faces multiple challenges, including potential toxic side effects, complex manufacturing processes, and impaired hypoxic targeting. Here, based on the excellent biocompatibility and distinctive metabolic ability of natural anaerobic sulfate-reducing...

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Main Authors: Mengna Dong, Xinhui Yang, Wenqian Zhang, Yuzhi Qiu, Peng Song, Hongfang Liu, Yajiang Yang, Xiangliang Yang, Qin Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61675-4
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author Mengna Dong
Xinhui Yang
Wenqian Zhang
Yuzhi Qiu
Peng Song
Hongfang Liu
Yajiang Yang
Xiangliang Yang
Qin Wang
author_facet Mengna Dong
Xinhui Yang
Wenqian Zhang
Yuzhi Qiu
Peng Song
Hongfang Liu
Yajiang Yang
Xiangliang Yang
Qin Wang
author_sort Mengna Dong
collection DOAJ
description Abstract Anaerobic bacteria-mediated tumor therapy faces multiple challenges, including potential toxic side effects, complex manufacturing processes, and impaired hypoxic targeting. Here, based on the excellent biocompatibility and distinctive metabolic ability of natural anaerobic sulfate-reducing bacteria (SRB) to dissimilate sulfate into sulfide, we construct in situ-biosynthesized ferrous sulfide nanoparticle-SRB (FeS@SRB) biohybrid to enhance tumor-targeted therapy. Interestingly, SRB acts as both a biosynthesis factory and active tumor-targeted delivery vehicles. Our systematic studies reveal that FeS@SRB has excellent biosafety and tumor targeting capabilities, achieving over 50% tumor delivery efficiency in female mice post-intravenous injection, which is 17 times higher than that of conventional chemically-synthesized FeS@BSA nanoparticles. Upon near-infrared laser irradiation, FeS@SRB hybrids exhibit synergistic photothermal-chemodynamic effect, amplifying oxidative stress to trigger tumor cells ferroptosis and apoptosis, thereby effectively suppressing both subcutaneous and orthotopic tumor growth. This SRB-based therapeutic strategy expands research into tumor-targeting platforms and the biosynthesis of metal sulfide nanoparticles for enhanced tumor therapy.
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institution Kabale University
issn 2041-1723
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publishDate 2025-07-01
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spelling doaj-art-5807108bf23f4158a2ab20b7e4b257bf2025-08-20T03:46:23ZengNature PortfolioNature Communications2041-17232025-07-0116112110.1038/s41467-025-61675-4Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapyMengna Dong0Xinhui Yang1Wenqian Zhang2Yuzhi Qiu3Peng Song4Hongfang Liu5Yajiang Yang6Xiangliang Yang7Qin Wang8Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyNational Engineering Research Center for NanomedicineHubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and TechnologyAbstract Anaerobic bacteria-mediated tumor therapy faces multiple challenges, including potential toxic side effects, complex manufacturing processes, and impaired hypoxic targeting. Here, based on the excellent biocompatibility and distinctive metabolic ability of natural anaerobic sulfate-reducing bacteria (SRB) to dissimilate sulfate into sulfide, we construct in situ-biosynthesized ferrous sulfide nanoparticle-SRB (FeS@SRB) biohybrid to enhance tumor-targeted therapy. Interestingly, SRB acts as both a biosynthesis factory and active tumor-targeted delivery vehicles. Our systematic studies reveal that FeS@SRB has excellent biosafety and tumor targeting capabilities, achieving over 50% tumor delivery efficiency in female mice post-intravenous injection, which is 17 times higher than that of conventional chemically-synthesized FeS@BSA nanoparticles. Upon near-infrared laser irradiation, FeS@SRB hybrids exhibit synergistic photothermal-chemodynamic effect, amplifying oxidative stress to trigger tumor cells ferroptosis and apoptosis, thereby effectively suppressing both subcutaneous and orthotopic tumor growth. This SRB-based therapeutic strategy expands research into tumor-targeting platforms and the biosynthesis of metal sulfide nanoparticles for enhanced tumor therapy.https://doi.org/10.1038/s41467-025-61675-4
spellingShingle Mengna Dong
Xinhui Yang
Wenqian Zhang
Yuzhi Qiu
Peng Song
Hongfang Liu
Yajiang Yang
Xiangliang Yang
Qin Wang
Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapy
Nature Communications
title Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapy
title_full Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapy
title_fullStr Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapy
title_full_unstemmed Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapy
title_short Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapy
title_sort living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor targeted therapy
url https://doi.org/10.1038/s41467-025-61675-4
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