A Donor–Donor‐π‐Acceptor–Acceptor Type Photosensitizer for Efficient Photo‐Inactivation of Pathogens Within Biofilms and Host Cells

Antibacterial photodynamic therapy (aPDT) is a promising strategy for combating prevalent antibiotic-resistant bacteria. However, development of efficient aPDT agents that can simultaneously eradicate resistant pathogens within biofilms and host cells with good biocompatibility remains a big challenge. Herein, three novel D-D-π-A-A type dyes (TPATA, TPATC, and TPATPy) were designed and synthesized. TPATPy can efficiently produce reactive oxygen species (ROS) mainly through type I mechanism, which is beneficial for overcoming hypoxia within biofilms. Besides, introduction of pyridinium cations in TPATPy enhances the binding ability with negatively charged bacteria and biofilms through electrostatic interactions. Therefore, TPATPy not only exhibited excellent aPDT activity toward planktonic bacteria, but also destroyed mature biofilms and the embedded pathogens. Moreover, TPATPy could selectively and efficiently photo-inactivate intracellular methicillin-resistant Staphylococcus aureus (MRSA), being more potent than vancomycin. So far as we know, TPATPy should be the first example that can simultaneously eradicate intractable pathogens within biofilms and host cells. The efficacy and safety of TPATPy in accelerating wound healing have also been demonstrated in an MRSA-infected skin wound model in mice. These results may provide new ideas for developing multifunctional aPDT agents to solve the intractable problems in antibacterial treatment.