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
  • 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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