Potentiating hypoxic microenvironment for antibiotic activation by photodynamic therapy to combat bacterial biofilm infections

Traditional antibiotic treatment has limited efficacy for the drug-tolerant bacteria present in biofilms because of their unique metabolic conditions in the biofilm infection microenvironment. Modulating the biofilm infection microenvironment may influence the metabolic state of the bacteria and provide alternative therapeutic routes. In this study, photodynamic therapy is used not only to eradicate methicillin-resistant Staphylococcus aureus biofilms in the normoxic condition, but also to potentiate the hypoxic microenvironment, which induces the anaerobic metabolism of methicillin-resistant Staphylococcus aureus and activates the antibacterial activity of metronidazole. Moreover, the photodynamic therapy-activated chemotherapy can polarize the macrophages to a M2-like phenotype and promote the repair of the biofilm infected wounds in mice. This biofilm infection microenvironment modulation strategy, whereby the hypoxic microenvironment is potentiated to synergize photodynamic therapy with chemotherapy, provides an alternative pathway for efficient treatment of biofilm-associated infections. Bacteria in biofilms present unique metabolic conditions that limit the traditional antibiotic treatment. Here, the authors show a photodynamic therapy-activated chemotherapy potentiating the hypoxia of biofilms of methicillin-resistant Staphylococcus aureus, by developing hyaluronic acid nanoparticles functionalized with chlorin e6 and metronidazole.

Automated summary

Traditional antibiotic treatment is not very effective against bacteria in biofilms due to their unique metabolic conditions. This study explores the use of photodynamic therapy to eliminate methicillin-resistant Staphylococcus aureus biofilms and enhance the hypoxic microenvironment, which induces anaerobic metabolism and activates the antibacterial activity of metronidazole. Additionally, the activated chemotherapy can promote the repair of biofilm-infected wounds by polarizing macrophages to a specific phenotype.