Photodynamic therapy for infections: clinical applications

Abstract

Background and objective: Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT.

Study design/materials and methods: The published peer-reviewed literature was reviewed between 1960 and 2011.

Results: The basics of antimicrobial PDT are discussed. Clinical applications of antimicrobial PDT to localized viral infections caused by herpes and papilloma viruses, and nonviral dermatological infections such as acne and other yeast, fungal and bacterial skin infections are covered. PDT has been used to treat bacterial infections in brain abscesses and non-healing ulcers. PDT for dental infections including periodontitis and endodontics has been well studied. PDT has also been used for cutaneous Leishmaniasis. Clinical trials of PDT and blue light alone therapy for gastric Helicobacter pylori infection are also covered.

Conclusion: As yet clinical PDT for infections has been mainly in the field of dermatology using 5-aminolevulanic acid and in dentistry using phenothiazinium dyes. We expect more to see applications of PDT to more challenging infections using advanced antimicrobial photosensitizers targeted to microbial cells in the years to come.

Fig. 1

Photochemical mechanisms in PDT. Ground state photosensitizer molecule absorbs light that excites it to singlet state that can lose energy by fluorescence or can undergo intersystem crossing to long-lived PS triplet state that can carry out photochemistry or lose its energy by phosphorescence. Subsequently this photochemistry leads local production of reactive oxygen species such as singlet oxygen (Type II) or superoxide (Type I) that are cytotoxic to microbial cells and to host cells.

Fig. 2

Cell wall structures of microbial pathogens. A: Gram-negative bacteria. B: Gram-positive bacteria. C: Fungal cells.

Fig. 3

Chemical structures of photosensitizers that have been used in clinical applications of antimicrobial PDT. (1) Methylene blue, (2) toluidine blue O, (3) neutral red, (4) PP904 phenothiazinium dye, (5) Protoporphyrin IX formed from ALA, MAL or endogenously produced by bacteria, (6) hematoporphyrin derivative, (7) conjugate between polyethylenimine and chlorin(e6).

Fig. 4

Heme biosynthetic pathways responsible for formation of PPIX from ALA. A: Porphyrin synthesis in Gram-negative bacteria. B: Porprhyrin synthesis is host mammalian cells.

Fig. 5

Schematic depiction of the range of human infections that have been clinically treated with PDT.