2. Academic Validation
  3. Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections

Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections

  • Bioact Mater. 2024 Jan 24:35:82-98. doi: 10.1016/j.bioactmat.2024.01.020.
Dongdong Xu 1,  Jun Hu 2,  Jiawei Mei 3,  Jun Zhou 4,  Zhengxi Wang 3,  Xudong Zhang 3,  Quan Liu 3,  Zheng Su 3,  Wanbo Zhu 4,  Hongjian Liu 1,  Chen Zhu 3
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR China.
  • 2 Department of Laboratory Medicine, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, PR China.
  • 3 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.
  • 4 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.
PMID: 38283386 DOI: 10.1016/j.bioactmat.2024.01.020
Abstract

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.

Keywords

Implant-related infections; Interferon; Neutrophil activation; Systemic immunotherapy; cGAS-STING pathway.

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