Surface charge switchable fluorinated small molecular micelles for enhanced photodynamic therapy for bacterial infections

Photodynamic therapy (PDT) employs reactive oxygen species (ROS) from a photosensitizer (PS) under light, inhibiting multi-drug resistance in bacteria. However, hypoxic conditions in infection sites and biofilms challenge PDT efficiency. We developed fluorinated small molecular micelles (PF-CBMs) as PS carriers to address this, relieving hypoxia and enhancing PS penetration into biofilms. Perfluorocarbons in PF-CBMs transport more oxygen due to their excellent oxygen-dissolving capability. Fluorination enhances loading capacity and serum stability, reduces premature release, and improves cellular uptake, to improve PDT efficacy. PF-CBMs, with acid-induced surface charge transformation, exhibit superior biofilm penetration, resulting in increased antibiofilm activity of PDT. Compared to fluorine-free micelles (PC-CBMs), PF-CBMs demonstrate better serum stability, higher drug loading, and reduced premature release, leading to significantly improved antibacterial efficacy in vitro and in vivo . In conclusion, fluorinated micelles with surface charge reversal enhance PDT for antibacterial and antibiofilm applications.