Novel porphyrin derivative containing cations as new photodynamic antimicrobial agent with high efficiency

Bacterial infections from chronic wounds affect about 175 million people each year and are a significant clinical problem. Through the integration of photodynamic therapy (PDT) and chemotherapy, a new photosensitizer consisting of ammonium salt N,N-bis-(2-hydroxyethyl)-N-(6-(4-(10,15,20-trimesitylporphyrin-5-yl) phenoxy) hexane)-N-methanaminium bromide, TMP⁽⁺⁾ was successfully synthesized with a total reaction yield of 10%. The novel photosensitizer consists of two parts, a porphyrin photosensitizer part and a quaternary ammonium salt part, to achieve the synergistic effect of photodynamic and chemical antibacterial activity. With the increase of TMP⁽⁺⁾ concentration, the diameter of the PCT fiber membranes (POL/COL/TMP⁽⁺⁾; POL, polycaprolactone; COL, collagen) gradually increased, which was caused by the charge of the quaternary ammonium salt. At the same time, the antibacterial properties were gradually improved. We finally selected the PCT 0.5% group for the antibacterial experiment, with excellent performance in fiber uniformity, hydrophobicity and biosafety. The antibacterial experiment showed that the modified porphyrin TMP⁽⁺⁾ had a better antibacterial effect than others. In vivo chronic wound healing experiments proved that the antibacterial and anti-inflammatory effect of the PCTL group was the best, further confirmed by H&E histological analysis, immunofluorescence and immunohistochemistry mechanism experiments. This research lays the foundation for the manufacture of novel molecules that combine chemical and photodynamic strategies.