pH-Responsive and Nanoenzyme-Loaded Artificial Nanocells Relieved Osteomyelitis Efficiently by Synergistic Chemodynamic and Cuproptosis Therapy

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.