Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy

Biofilms are chief culprits of most intractable infections and pose great threats to human health. Conventional antibiotic therapies are hypodynamic to biofilms due to their strong drug resistance, closely related with biofilm hypoxia. A new strategy for enhanced antibiotic therapy by relieving biofilm hypoxia is reported here. A two-step sequential delivery strategy is fabricated using perfluorohexane (PFH)-loaded liposomes (lip) as oxygen (O₂) carriers (denoted as lip@PFH@O₂) and commercial antibiotics. The results indicate that the two-step sequential treatment exhibits much lower minimum bactericidal concentrations than the antibiotic treatment alone. In this design, the lip@PFH@O₂ holds positively charged surface for better biofilm penetration. After penetrating into biofilm, oxygen can be released from lip@PFH@O₂ by inches, which greatly relieves biofilm hypoxia. With the relief of hypoxia, the quorum sensing and the drug efflux pumps of bacteria are suppressed by restraining related gene expression, leading to the reduced antibiotic resistance. Furthermore, the in vivo experimental results also demonstrate that lip@PFH@O₂ can effectively relieve biofilm hypoxia and enhance therapeutic efficacy of antibiotics. As a proof-of-concept, this research provides an innovative strategy for enhanced antibiotic therapy by relieving hypoxia, which may hold a bright future in combating biofilm-associated infections.

Keywords: antibiotic resistance; antibiotics; biofilms; hypoxia; perfluorohexane.