The original report of photoantimicrobial activity of the dyes acridine or eosin against Paramecium caudatum was published in 1900 by Raab. The same approach was applied to tumour cells by von Tappeiner and Jesionek in 1905. Most research concentrated on the use of this photodynamic inactivation technology as a cancer therapy but in the 1990s there was a growing realisation of its potential for treating bacterial infections.
The Photoantimicrobial Concept
Photoantimicrobials are photosensitisers which when exposed to light can form reactive oxygen species (ROS) such as singlet oxygen, superoxide anions and hydroxyl radicals by two alternative pathways. ROS have a broad spectrum of activity and can destroy numerous microbial targets including proteins, lipids and nucleic acids, which makes it unlikely that the microbes can develop resistance. Entry of the photoantimicrobial into the microbial cell is also not required for cell killing. which further prevents the development of resistance.
Photoantimicrobials are active against both Gram-positive and Gram-negative bacteria, together with fungal, viral and protozoal targets, and exert their killing effects very rapidly.
Effective photoantimicrobials such as gentian violet and methylene blue have been used for over one hundred years with no safety concerns. Currently photoantimicrobials are only approved for clinical use in dentistry as an adjuvant approach. A majority of photoantimicrobials are phenothiazinium salts, porphyrins, phlhalocyanines, or natural products such as curcumin (approved as the food additive E100), riboflavin (vitamin B2) and hypericin, whose biocompatibility is high.
Advantages of Photoantimicrobials
- Broad spectrum activity against both Gram-positive and Gram-negative bacterial pathogens, fungi, viruses and protozoan
- Killing by photoantimicrobials occurs in seconds
- Photoantimicrobial agents with a cationic charge selectively bind to microbial cells and not to mammalian cells
- Binding of photoantimicrobials to microbial cells is rapid whilst their uptake into mammalian cells is slow giving good selectivity
- Resistance to photoantimicrobials difficult to achieve due to the number of different targets
- Photoantimicrobials, unlike antibiotics, are effective against microbial biofilms
- Applications in veterinary medicine, management of plant pathogens, control of pathogens in fish farming, removal of pathogens in wastewater, incorporation of photoantimicrobials in materials as self-disinfecting surfaces, and inactivation of bioterrorist agents such as anthrax spores
Limitations of Photoantimicrobials
- The requirement for activation of photoantimicrobials by light would seem to restrict their use to treating localized infections however developments in fibre-optic technology mean that most regions of the anatomy are accessible
- Very few clinical trials have been carried out with photoantimicrobials with only three agents (methylene blue, toluidine blue O and indocyanine green) currently approved for clinical use in dentistry