Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a new promising strategy to
eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria, yeasts and fungi. The search for
new approaches that can kill bacteria but do not induce the appearance of undesired drug-resistant strains suggests that
PDT may have advantages over traditional antibiotic therapy. PDT is a non-thermal photochemical reaction that involves
the simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS). Several PS have been studied for
their ability to bind to bacteria and efficiently generate reactive oxygen species (ROS) upon photo-stimulation. ROS are
formed through type I or II mechanisms and may inactivate several classes of microbial cells including Gram-negative
bacteria such as Pseudomonas aeruginosa, which are typically characterized by an impermeable outer cell membrane that
contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the sensitive inner membrane and cell wall.
This review covers significant peer-reviewed articles together with US and World patents that were filed within the past
few years and that relate to the eradication of Gram-negative bacteria via PDI or PDT. It is organized mainly according to
the nature of the PS involved and includes natural or synthetic food dyes; cationic dyes such as methylene blue and toluidine
blue; tetrapyrrole derivatives such as phthalocyanines, chlorins, porphyrins, chlorophyll and bacteriochlorophyll derivatives;
functionalized fullerenes; nanoparticles combined with different PS; other formulations designed to target PS to
bacteria; photoactive materials and surfaces; conjugates between PS and polycationic polymers or antibodies; and permeabilizing
agents such as EDTA, PMNP and CaCl2. The present review also covers the different laboratory animal models
normally used to treat Gram-negative bacterial infections with antimicrobial PDT.
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114.