Relief of Biofilm Hypoxia: A Synergistic Approach with Cyanobacteria and Chlorin e6-Loaded Nanoparticles

Abstract Photodynamic therapy (PDT) involves the use of photosensitizers, oxygen, and light to generate reactive oxygen species (ROS) for the effective destruction of cancer cells or bacteria. However, in biofilm bacterial infections, the presence of hypoxia significantly reduces the efficacy of PDT. To address this issue, we have developed a synergistic approach wherein Synechococcus elongatus (PCC 7942), cyanobacteria are loaded into a sodium alginate hydrogel, and chlorin e6 (Ce6) is conjugated with mesoporous silica nanoparticles (Ce6-MSNs). Cyanobacteria are photosynthetic organisms capable of releasing oxygen when exposed to 660 nm light. This property facilitates the effective production of ROS by Ce6-MSNs, even in hypoxic conditions, potentially enabling more effective PDT against MRSA planktonic bacteria and biofilm. Our results demonstrate that this system can maintain oxygen generation capacity for the test period of 30 days, thereby enhancing ROS production under hypoxic conditions. In summary, this innovative system combines cyanobacteria's photosynthetic oxygen generation with Ce6-MSNs' ROS production capabilities to address the challenge of hypoxia in biofilm infections. The promising results suggest its potential for improving the efficacy of PDT against bacterial infections, including drug-resistant strains such as MRSA. Graphical Abstract