Synthesis of photosensitizer-deferoxamine B conjugates and evaluation of their antimicrobial photodynamic activity

Abstract

Iron is indispensable for microorganisms thriving in aerobic conditions. Bacteria employ siderophores to acquire Fe(III), with their iron complexes transported across the bacterial cell membrane. A strategy for delivering antibiotics to bacteria involves sideromycin, exploiting the siderophore-mediated iron uptake pathway. Photodynamic therapy (PDT), comprising photosensitizers, oxygen, and light, generates reactive oxygen species (ROS) that inflict damage on intracellular components such as DNA, protein, and lipid. Antimicrobial photodynamic therapy (aPDT), stands as an innovative approach for combatting diverse bacterial strains. In this research, photosensitizer-deferoxamine B conjugates (Ps-DFOs) were synthesized, characterized, and examined for photodynamic inactivation. We chose hydrophobic porphyrin (TPP), cationic porphyrin (TMPyP), metalloporphyrin (PdTMPyP), and chlorin (chlorin e6) as the photosensitizers, and deferoxamine B as the siderophore. Ps-DFOs exhibited distinct UV-vis absorption peaks characteristic for each photosensitizer indicating minimal changes in the photophysical properties of the photosensitizers. In biological assay, TMPyP-DFO is the most potent agent against the Gram-negative A. baumannii (MIC50 = 12.5 µM) and Gram-positive S. aureus (MIC50 = 6.3 µM) under visible light irradiation conditions. The antimicrobial activity decreased more than twofold under dark conditions; therefore, selective killing of bacterial cells is possible by light irradiation. Our results suggest that the conjugation of cationic photosensitizer (TMPyP) with deferoxamine promotes the uptake of the photosensitizer, overcoming the inherent permeability challenges in bacteria. These observations provide insights into the strategy of deferoxamine B conjugation in facilitating the internalization of various antimicrobial cargos.