Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections
Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a ''cold tumor''-like immune silent microenvironment,...
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KeAi Communications Co., Ltd.
2024-05-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24000306 |
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| author | Dongdong Xu Jun Hu Jiawei Mei Jun Zhou Zhengxi Wang Xudong Zhang Quan Liu Zheng Su Wanbo Zhu Hongjian Liu Chen Zhu |
| author_facet | Dongdong Xu Jun Hu Jiawei Mei Jun Zhou Zhengxi Wang Xudong Zhang Quan Liu Zheng Su Wanbo Zhu Hongjian Liu Chen Zhu |
| author_sort | Dongdong Xu |
| collection | DOAJ |
| description | Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a ''cold tumor''-like immune silent microenvironment, allowing the persistence of IRIs. To address this challenge, an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum (CFCP) was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response. Specifically, enhanced sonodynamic therapy (SDT) from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA (dsDNA). Immunogenic dsDNA promoted dendritic cell (DC) maturation through activation of the stimulator of interferon gene (STING) and amplified the immune stimulation of neutrophils via interferon-β (IFN-β). At the same time, enhanced BAA presentation aroused humoral immunity in B and T cells, creating long-term resistance to repetitive infections. Encouragingly, CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention. |
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| id | doaj.art-1638223513fd4925b79180915f25ffa7 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2025-03-22T04:00:28Z |
| publishDate | 2024-05-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Bioactive Materials |
| spelling | doaj.art-1638223513fd4925b79180915f25ffa72024-04-28T10:12:48ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-05-01358298Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infectionsDongdong Xu0Jun Hu1Jiawei Mei2Jun Zhou3Zhengxi Wang4Xudong Zhang5Quan Liu6Zheng Su7Wanbo Zhu8Hongjian Liu9Chen Zhu10Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR ChinaDepartment of Laboratory Medicine, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, PR ChinaDepartment of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200233, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, PR ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, PR China; Corresponding author.Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200233, PR China; Corresponding author.Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR China; Corresponding author.Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, PR China; Corresponding author.Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a ''cold tumor''-like immune silent microenvironment, allowing the persistence of IRIs. To address this challenge, an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum (CFCP) was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response. Specifically, enhanced sonodynamic therapy (SDT) from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA (dsDNA). Immunogenic dsDNA promoted dendritic cell (DC) maturation through activation of the stimulator of interferon gene (STING) and amplified the immune stimulation of neutrophils via interferon-β (IFN-β). At the same time, enhanced BAA presentation aroused humoral immunity in B and T cells, creating long-term resistance to repetitive infections. Encouragingly, CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.http://www.sciencedirect.com/science/article/pii/S2452199X24000306Implant-related infectionsSystemic immunotherapycGAS-STING pathwayInterferonNeutrophil activation |
| spellingShingle | Dongdong Xu Jun Hu Jiawei Mei Jun Zhou Zhengxi Wang Xudong Zhang Quan Liu Zheng Su Wanbo Zhu Hongjian Liu Chen Zhu Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections Bioactive Materials Implant-related infections Systemic immunotherapy cGAS-STING pathway Interferon Neutrophil activation |
| title | Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections |
| title_full | Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections |
| title_fullStr | Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections |
| title_full_unstemmed | Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections |
| title_short | Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections |
| title_sort | nanoadjuvant triggered sting activation evokes systemic immunotherapy for repetitive implant related infections |
| topic | Implant-related infections Systemic immunotherapy cGAS-STING pathway Interferon Neutrophil activation |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24000306 |
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