Light based anti-infectives: ultraviolet C irradiation, photodynamic therapy, blue light, and beyond

Abstract

Owing to the worldwide increase in antibiotic resistance, researchers are investigating alternative anti-infective strategies to which it is supposed microorganisms will be unable to develop resistance. Prominent among these strategies, is a group of approaches which rely on light to deliver the killing blow. As is well known, ultraviolet light, particularly UVC (200-280 nm), is germicidal, but it has not been much developed as an anti-infective approach until recently, when it was realized that the possible adverse effects to host tissue were relatively minor compared to its high activity in killing pathogens. Photodynamic therapy is the combination of non-toxic photosensitizing dyes with harmless visible light that together produce abundant destructive reactive oxygen species (ROS). Certain cationic dyes or photosensitizers have good specificity for binding to microbial cells while sparing host mammalian cells and can be used for treating many localized infections, both superficial and even deep-seated by using fiber optic delivered light. Many microbial cells are highly sensitive to killing by blue light (400-470 nm) due to accumulation of naturally occurring photosensitizers such as porphyrins and flavins. Near infrared light has also been shown to have antimicrobial effects against certain species. Clinical applications of these technologies include skin, dental, wound, stomach, nasal, toenail and other infections which are amenable to effective light delivery.

Figure 1

Spectrum of ultraviolet irradiation.

Figure 2

Schematic illustration of photodynamic action. The PS initially absorbs a photon that excites it to the first excited singlet state and this can relax to the more long-lived triplet state. The triplet PS can interact with molecular oxygen in two pathways, Type I and Type II, leading to the formation of reactive oxygen species (ROS) and singlet oxygen ¹O₂, respectively. The formation of ROS and ¹O₂ can chemically attack a very wide range of biomolecules.

Figure 3

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

Figure 4

Chemical structures of PSs described in this review. (A) Cationic phthalocyanine, Zn-PC-Me; (B) Hydroxygallium(III) 2,3,9,10,16,17,23,24-octakis-[3-(N-methyl) -pyridyloxy]-phthalocyanine octaiodide; (C) Toluidine blue O; (D) 3,7-Bis(N,N-dibutylamino) phenothiazinium bromide, PPA904; (E) 5-Phenyl-10,15,20-tris(N-methyl-4-pyridyl)-porphine trichloride, Sylsens B; (F) Rose Bengal; (G) Riboflavin; (H) Curcumin; (I) Polyethylenimine chlorin(e6), PEI-ce6; (J) Merocyanine 540; (K) Poly-S-lysine porphyrin conjugate, pL-TMPP; (L) Functionalized fullerene, C60(>ME1N6+C3); (M) Tri-meso (N-methyl-pyridyl), meso (N-tetradecyl-pyridyl) porphine, C14.

Figure 5

Improvements of severe inflammatory acne treated by 15% ALA-PDT (a c) and control (only red light alone) (d f). (a, d) before treatment; (b, e) 2 weeks after four consecutive treatments; (c, f) at follow-up visit after 24 weeks [213].