Photodynamic Therapy for Cancer and for Infections: What Is the Difference?

Abstract

Photodynamic therapy (PDT) was discovered over one hundred years ago when it was observed that certain dyes could kill microorganisms when exposed to light in the presence of oxygen. Since those early days, PDT has mainly been developed as a cancer therapy and as a way to destroy proliferating blood vessels. However, recently it has become apparent that PDT may also be used as an effective antimicrobial modality and a potential treatment for localized infections. This review discusses the similarities and differences between the application of PDT for the treatment of microbial infections and for cancer lesions. Type I and type II photodynamic processes are described, and the structure-function relationships of optimal anticancer and antimicrobial photosensitizers are outlined. The different targeting strategies, intracellular photosensitizer localization, and pharmacokinetic properties of photosensitizers required for these two different PDT applications are compared and contrasted. Finally, the ability of PDT to stimulate an adaptive or innate immune response against pathogens and tumors is also covered.

Figure 1

Jablonski diagram showing the photochemistry arising from the PS triplet state. Type I photochemistry can produce hydroxyl radicals that may be efficient in destroying microbial cells. Type II produces singlet oxygen that may be efficient in destroying cancer cells, while peroxynitrite (formed from superoxide and nitric oxide) may be efficient in destroying tumor blood vessels.

Figure 2

Comparison of PS localization in cancer cells and bacteria. In mammalian cancer cells, PS (red dots) localize in various intracellular organelles such as lysosomes, mitochondria, the endoplasmic reticulum, Golgi apparatus, and plasma membrane, depending on the precise chemical structure and the incubation time. In Gram-positive bacteria, PS can penetrate through the cell wall to the plasma membrane and even get inside and bind to chromosomal DNA, while in Gram-negative cells penetration of the PS through the outer cell wall is more difficult.

Figure 3

Comparison of PS and light delivery routes between PDT for cancer and PDT for infections. PDT for cancer usually employs intravenous injection of the PS followed by laser illumination, while PDT for infections is likely to use topical PS application followed perhaps by light delivery from a light-emitting bandage.

Figure 4

Comparison of the immune cells that may be involved in the stimulation of immune response after PDT for cancer and PDT for infections. In the case of cancer, antigen-presenting dendritic cells (DC) are crucial and antigen-specific T lymphocytes play a major role in tumor destruction. For infections, it is likely that innate immune cells such as macrophages and especially neutrophils play a major role in the effect of PDT in preventing bacterial infection.