A H2S‐Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation

Abstract Photodynamic therapy (PDT) is a promising treatment against bacteria‐caused infections. By producing large amounts of reactive oxygen species (ROS), PDT can effectively eliminate pathogenic bacteria, without causing drug resistance. However, excessive ROS may also impose an oxidative stress on surrounding tissues, resulting in local inflammation. To avoid this major drawback and limit pro‐inflammation during PDT, this work prepared a supramolecular photosensitizer ( TPP‐CN/CP5 ) based on host‐guest interactions between a cysteine‐responsive cyano‐tetraphenylporphyrin ( TPP‐CN ) and a water‐soluble carboxylatopillar[5]arene ( CP5 ). TPP‐CN/CP5 not only possesses excellent photodynamic antibacterial properties, but also shows good anti‐inflammatory and cell protection capabilities. Under 660 nm light irradiation, TPP‐CN/CP5 could rapidly produce abundant ROS for sterilization. After the PDT process, the addition of cysteine (Cys) triggers the release of H 2 S from TPP‐CN . H 2 S then stops the induced inflammation by inhibiting the production of related inflammatory factors. Both in vitro and in vivo experiments show the excellent antibacterial effects and anti‐inflammatory abilities of TPP‐CN/CP5 . These results will certainly promote the clinical application of PDT in the treatment of bacterial infectious diseases.