Nanofabricated Bacterial Cell Walls with Intrinsic Peroxidase‐Mimicking and Sonodynamic Activities for Cancer Combination Treatment

Abstract Bacterial cancer therapy recently has been attracting more and more attention because of its multiple functions to fight cancer. Porphyromonas gingivalis (Pg), a Gram‐negative pathogenic bacterium, acquires protoporphyrin IX (PpIX) and iron from heme and synthesizes abundant µ‐oxo bisheme o...

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Main Authors: Meng Yang, Yang Meng, Junling Li, Liya Bai, Yuanyuan Cheng, Yuanyuan Liu, Mingxin Cao, Xiaoying Yang, Yinsong Wang, Yang Liu
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202505310
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author Meng Yang
Yang Meng
Junling Li
Liya Bai
Yuanyuan Cheng
Yuanyuan Liu
Mingxin Cao
Xiaoying Yang
Yinsong Wang
Yang Liu
author_facet Meng Yang
Yang Meng
Junling Li
Liya Bai
Yuanyuan Cheng
Yuanyuan Liu
Mingxin Cao
Xiaoying Yang
Yinsong Wang
Yang Liu
author_sort Meng Yang
collection DOAJ
description Abstract Bacterial cancer therapy recently has been attracting more and more attention because of its multiple functions to fight cancer. Porphyromonas gingivalis (Pg), a Gram‐negative pathogenic bacterium, acquires protoporphyrin IX (PpIX) and iron from heme and synthesizes abundant µ‐oxo bisheme on its cell walls (CWs). For the first time, it is found that the CWs extracted from Pg has intrinsic peroxidase (POD)‐mimicking and sonodynamic activities owing to the presence of µ‐oxo bisheme. In this study, the CWs of Pg are nanofabricated to form the CW vesicles (CWV) containing a large amount of lipopolysaccharide (LPS) and further encapsulated doxorubicin (DOX) to prepare DOX‐loaded CWV (DOX@CWV), hoping to eradicate cancer by combining sonodynamic therapy (SDT), chemotherapy, and bacterial immunotherapy. The results confirmed that DOX@CWV can catalyze the conversion of H2O2 into O2 and consume the reduced glutathione (GSH), and thus greatly boost their own sonodynamic performance upon ultrasonic irradiation. Both in vitro and in vivo, DOX@CWV efficiently inhibited cancer growth by combining SDT and chemotherapy, and also exerted synergistic anticancer immune effects of bacterial immunotherapy and SDT. In summary, the findings not only contribute a promising bacterial therapeutic agent but also provide a combination strategy for clinical cancer treatment.
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spelling doaj-art-6d2b2bd393a24f95aa6d103538ae3f1f2025-08-20T11:56:10ZengWileyAdvanced Science2198-38442025-08-011230n/an/a10.1002/advs.202505310Nanofabricated Bacterial Cell Walls with Intrinsic Peroxidase‐Mimicking and Sonodynamic Activities for Cancer Combination TreatmentMeng Yang0Yang Meng1Junling Li2Liya Bai3Yuanyuan Cheng4Yuanyuan Liu5Mingxin Cao6Xiaoying Yang7Yinsong Wang8Yang Liu9Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) The Province and Ministry Co‐sponsored Collaborative Innovation Center for Medical Epigenetics International Joint Laboratory of Ocular Diseases (Ministry of Education) Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University Tianjin 300070 ChinaKey Laboratory of Immune Microenvironment and Disease (Ministry of Education) The Province and Ministry Co‐sponsored Collaborative Innovation Center for Medical Epigenetics International Joint Laboratory of Ocular Diseases (Ministry of Education) Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University Tianjin 300070 ChinaDepartment of Genetics School of Basic Medical Sciences Tianjin Medical University Tianjin 300070 ChinaKey Laboratory of Immune Microenvironment and Disease (Ministry of Education) The Province and Ministry Co‐sponsored Collaborative Innovation Center for Medical Epigenetics International Joint Laboratory of Ocular Diseases (Ministry of Education) Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University Tianjin 300070 ChinaDepartment of Pharmacology Tianjin Key Laboratory of Inflammatory Biology Center for Cardiovascular Diseases Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) The Province and Ministry Co‐sponsored Collaborative Innovation Center for Medical Epigenetics Tianjin Medical University Tianjin 300070 ChinaDepartment of Genetics School of Basic Medical Sciences Tianjin Medical University Tianjin 300070 ChinaDepartment of Orthodontics Tianjin Medical University School and Hospital of Stomatology Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, and Institute of Stomatology Tianjin 300070 ChinaKey Laboratory of Immune Microenvironment and Disease (Ministry of Education) The Province and Ministry Co‐sponsored Collaborative Innovation Center for Medical Epigenetics International Joint Laboratory of Ocular Diseases (Ministry of Education) Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University Tianjin 300070 ChinaKey Laboratory of Immune Microenvironment and Disease (Ministry of Education) The Province and Ministry Co‐sponsored Collaborative Innovation Center for Medical Epigenetics International Joint Laboratory of Ocular Diseases (Ministry of Education) Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) School of Pharmacy Tianjin Medical University Tianjin 300070 ChinaDepartment of Hepatobiliary Cancer Liver Cancer Center Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin 300060 ChinaAbstract Bacterial cancer therapy recently has been attracting more and more attention because of its multiple functions to fight cancer. Porphyromonas gingivalis (Pg), a Gram‐negative pathogenic bacterium, acquires protoporphyrin IX (PpIX) and iron from heme and synthesizes abundant µ‐oxo bisheme on its cell walls (CWs). For the first time, it is found that the CWs extracted from Pg has intrinsic peroxidase (POD)‐mimicking and sonodynamic activities owing to the presence of µ‐oxo bisheme. In this study, the CWs of Pg are nanofabricated to form the CW vesicles (CWV) containing a large amount of lipopolysaccharide (LPS) and further encapsulated doxorubicin (DOX) to prepare DOX‐loaded CWV (DOX@CWV), hoping to eradicate cancer by combining sonodynamic therapy (SDT), chemotherapy, and bacterial immunotherapy. The results confirmed that DOX@CWV can catalyze the conversion of H2O2 into O2 and consume the reduced glutathione (GSH), and thus greatly boost their own sonodynamic performance upon ultrasonic irradiation. Both in vitro and in vivo, DOX@CWV efficiently inhibited cancer growth by combining SDT and chemotherapy, and also exerted synergistic anticancer immune effects of bacterial immunotherapy and SDT. In summary, the findings not only contribute a promising bacterial therapeutic agent but also provide a combination strategy for clinical cancer treatment.https://doi.org/10.1002/advs.202505310bacterial cell wallsbacterial immunotherapychemotherapyperoxidase‐mimicking activitysonodynamic therapy
spellingShingle Meng Yang
Yang Meng
Junling Li
Liya Bai
Yuanyuan Cheng
Yuanyuan Liu
Mingxin Cao
Xiaoying Yang
Yinsong Wang
Yang Liu
Nanofabricated Bacterial Cell Walls with Intrinsic Peroxidase‐Mimicking and Sonodynamic Activities for Cancer Combination Treatment
Advanced Science
bacterial cell walls
bacterial immunotherapy
chemotherapy
peroxidase‐mimicking activity
sonodynamic therapy
title Nanofabricated Bacterial Cell Walls with Intrinsic Peroxidase‐Mimicking and Sonodynamic Activities for Cancer Combination Treatment
title_full Nanofabricated Bacterial Cell Walls with Intrinsic Peroxidase‐Mimicking and Sonodynamic Activities for Cancer Combination Treatment
title_fullStr Nanofabricated Bacterial Cell Walls with Intrinsic Peroxidase‐Mimicking and Sonodynamic Activities for Cancer Combination Treatment
title_full_unstemmed Nanofabricated Bacterial Cell Walls with Intrinsic Peroxidase‐Mimicking and Sonodynamic Activities for Cancer Combination Treatment
title_short Nanofabricated Bacterial Cell Walls with Intrinsic Peroxidase‐Mimicking and Sonodynamic Activities for Cancer Combination Treatment
title_sort nanofabricated bacterial cell walls with intrinsic peroxidase mimicking and sonodynamic activities for cancer combination treatment
topic bacterial cell walls
bacterial immunotherapy
chemotherapy
peroxidase‐mimicking activity
sonodynamic therapy
url https://doi.org/10.1002/advs.202505310
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