2. Academic Validation
  3. pH-responsive and nanoenzyme-loaded artificial nanocells relieved osteomyelitis efficiently by synergistic chemodynamic and cuproptosis therapy

pH-responsive and nanoenzyme-loaded artificial nanocells relieved osteomyelitis efficiently by synergistic chemodynamic and cuproptosis therapy

  • Biomaterials. 2025 Feb:313:122762. doi: 10.1016/j.biomaterials.2024.122762.
Yuanhui Li 1,  Jian Li 1,  Yuxuan Zhong 1,  Qingshun Zhang 1,  Yuchun Wu 1,  Jinpeng Huang 1,  Kaicheng Pang 1,  Yuanyue Zhou 1,  Tong Xiao 1,  Zenghui Wu 2,  Wei Sun 3,  Chao He 4
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Guangdong Provincial Engineering Research Center for Biomedical Engineering, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China.
  • 2 Department of Orthopedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Guangdong Provincial Engineering Research Center for Biomedical Engineering, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China. Electronic address: 3094206329@qq.com.
  • 3 Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China. Electronic address: sunwei@gzhmu.edu.cn.
  • 4 Department of Orthopedic Surgery, Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Guangdong Provincial Engineering Research Center for Biomedical Engineering, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China. Electronic address: hechao101010@126.com.
PMID: 39178559 DOI: 10.1016/j.biomaterials.2024.122762
Abstract

Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic Antibiotics with debridements, which are not effective and lead to Antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant Bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and Cuproptosis induction. Notably, mRNA Sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, Oxidative Phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct Cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.

Keywords

Cuproptosis; Fenton reaction; Nanocell; Osteomyelitis; Reactive oxygen species (ROS).

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