pH-Responsive carrier-free nanoparticles based on teicoplanin and borneol for enhanced MRSA infectious wound healing

Bacterial infections severely threaten human health, and the drug resistance induced by long-term high-dose antibiotic use is a critical issue, which necessitates new antibacterial strategies. In this study, pH-responsive carrier-free nanoparticles (BF-TEI NPs) are fabricated based on the Schiff-base bonding between the hydrophilic antibiotic teicoplanin (TEI) and the hydrophobic antibacterial borneol 4-formylbenzoate (BF). Self-assembled BF-TEI NPs enable synchronous release of BF and TEI in infected sites for synergistic antibacterial effects via acidic microenvironment-triggered Schiff-base bond cleavage. Compared with the physical mixture of BF and TEI, BF-TEI NPs show lower in vitro minimum inhibitory and bactericidal concentrations against Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), indicating enhanced antibacterial activity. Moreover, BF-TEI NPs effectively eliminate MRSA at the in vivo infected sites and accelerate wound healing. Considering the good in vitro and in vivo biocompatibility and safety of BF-TEI NPs, the carrier-free self-assembly strategy of clinical antibiotics offers an innovative approach for overcoming drug resistance and improving infectious wound healing.