Efficient and Selective, In Vitro and In Vivo, Antimicrobial Photodynamic Therapy with a Dicationic Chlorin in Combination with KI

Various cationic photosensitizers employed in antimicrobial photodynamic therapy (aPDT) have the ability to photoinactivate planktonic bacteria under conditions of low phototoxicity to mammalian cells and without generating antimicrobial resistance (AMR). However, the photoinactivation of biofilms requires orders-of-magnitude higher photosensitizer concentrations, which become toxic to host cells. Remarkably, the bactericidal effect of a dicationic di-imidazolyl chlorin toward planktonic <i>S. aureus</i> and <i>E. coli</i> was observed in this work for concentrations below 400 nM under illumination at 660 nm and below 50 μM for the corresponding biofilms. At the latter concentrations, the chlorin is phototoxic toward human keratinocyte cells. However, in the presence of 50 mM KI, bactericidal concentrations are reduced to less than 50 nM for planktonic bacteria and to less than 1 μM for biofilms. It is shown that the potentiation with KI involves the triiodide anion. This potentiation elicits a bactericidal effect without appreciable cytotoxicity to keratinocytes. It becomes possible to selectively inactivate biofilms with aPDT. An exploratory study treating mice with wounds infected with <i>E. coli</i> expressing GFP with 20 μM chlorin and 120 J cm^-2 at 652 nm confirmed the potential of this chlorin to control localized infections.