Hydrophilic Porphyrin-Cationic Fluorene Conjugated Polymer Enhances Antibacterial Photodynamic Therapy for Bacterial Biofilm Destruction

Antibacterial photodynamic therapy (aPDT), known for its broad-spectrum antibacterial activity and low propensity for resistance, has garnered attention as a promising alternative to conventional antibacterial strategies. However, a key challenge remains: photosensitizer molecules struggle to penetrate bacterial biofilms in deep tissues. To overcome this hurdle, we developed a poly(porphyrin)- b -poly(fluorene) copolymer (PPF), integrating hydrophilic porphyrin molecules with fluorene. This innovative material boasts a high photosensitizer content and has the ability to spontaneously form stable nanoparticles (NPs) within aqueous solutions. The surface of these NPs is positively charged, facilitating effective attach to bacterial membranes and boost the permeability of bacterial outer and cytoplasmic membranes, induce depolarization of the cytoplasmic membrane, thereby disrupting the bacteria’s normal homeostasis. Moreover, the copolymer’s ability to generate a large amount of singlet oxygen through photodynamic therapy further exacerbates bacterial damage. In our experiments, the minimum inhibitory concentrations of PPF NPs combined with photodynamic therapy for Staphylococcus aureus and Escherichia coli were 16 μg/mL and 32 μg/mL, respectively. PPF NPs demonstrated the capacity to penetrate biofilm structures, effectively resisting wound infections, accelerating wound healing, and exhibiting moderate biosafety. Therefore, the cationic-integrated photodynamic antibacterial therapy provides crucial insights for addressing the challenge of photosensitizer molecular penetration through bacterial biofilms.