Photodynamic Therapy Targeted to Pathogens

Abstract

Photodynamic therapy (PDT) employs a non-toxic dye termed a photosensitizer (PS) together with low intensity visible light, which, in the presence of oxygen, produce cytotoxic species. PS can be targeted to its destination cell or tissue and, in addition, the irradiation can be spatially confined to the lesion giving PDT the advantage of dual selectivity. This promising approach can be used for various applications including microbial inactivation and the treatment of infections. Resistance to PDT has not been shown and multiantibiotic-resistant strains are as easily killed as naïve strains. It is known that Gram (+) bacteria are more sensitive to PDT as compared to Gram (-) species. However, the use of cationic PS or agents that increase the permeability of the outer membrane allows for the effective killing of Gram (-) organisms. Some PS have an innate positive charge, but our approach is to link PS to a cationic molecular vehicle such as poly-L-lysine. This modification dramatically increases PS binding to and penetrating through the negatively charged bacterial permeability barrier. Due to focused light delivery the use of PDT is possible only for localized infections. Nonetheless numerous diseases can be treated. Selectivity of the PS for microbes over host cells, accurate delivery of the PS into the infected area, and PDT dose adjustment help minimize side effects and give PDT an advantage over conventional therapy. There are only a few reports about the use of antimicrobial PDT in animal models and clinical trials. We have used genetically modified bioluminescent bacteria to follow the effect of PDT in infected wounds, burns, and soft tissue infections in mice. Not only were bacteria infecting wounds, burns, and abscesses killed, but mice were saved from death due to sepsis and wound healing was improved.