Refining antimicrobial photodynamic therapy: effect of charge distribution and central metal ion in fluorinated porphyrins on effective control of planktonic and biofilm bacterial forms

Barbara Pucelik, Agata Barzowska, Adam Sułek, Mateusz Werłos, Janusz M. Dąbrowski

Antibiotic resistance has become a critical global health issue, recognized within the One Health framework. Photodynamic inactivation of microorganisms (PDI) offers a promising non-invasive alternative, effective across a broad spectrum with minimal resistance risk. This study presents the synthesis, photophysical properties, and antimicrobial effects of a palladium(II)-porphyrin derivative (PdF2POH) along with its zinc(II) and free-base variants (ZnF2POH, F2POH). PdF2POH demonstrated exceptional reactive oxygen species (ROS) generation, including singlet oxygen (Φ△ = 0.93) and oxygen-centered radicals, confirmed through luminescence and fluorescent probe assays. All compounds exhibited strong activity against Gram-positive bacteria, with PdF2POH achieving a 6-log reduction in S. aureus viability, including biofilm disruption. PdF2POH-mediated PDI showed selectivity for bacterial over mammalian cells, particularly under lower blue light doses (up to 5 J/cm²). Its superior efficacy over ZnF2POH and F2POH is attributed to higher ROS production through both photochemical pathways. Furthermore, PdF2POH effectively eliminated bacteria in S. aureus-infected human keratinocytes while preserving cell viability. These findings highlight Pd(II)-porphyrin as a promising photosensitizer for combating bacterial infections, supporting further exploration in advanced infection models.

DOI: doi.org/10.1007/s43630-024-00538-1

Keywords: Antibiotic resistancePhotodynamic inactivation (PDI)PhotosensitizerPalladium(II)-porphyrin (PdF2POH)Reactive oxygen species (ROS)Singlet oxygenGram-positive bacteriaStaphylococcus aureusBiofilm disruptionZinc(II)-porphyrin (ZnF2POH)Human keratinocytesBacterial infection therapyOne Health framework