Photodynamic Therapy: Antimicrobial Treatment and Oxidative Disease Model

Abstract

Photodynamic therapy (PDT) is a photochemical method to induce oxidation on demand. Oxidation has benefits to biological function in signaling pathways but can also cause damaging oxidative stress (OS), associated with diseases such as aging, neurodegeneration, and cancer. PDT is commonly employed in medicine to neutralize tumors, eliminate microbes, rejuvenate skin, and to study oxidative stress mechanisms.

Antimicrobial PDT is a well-studied tool for infection clearing but has not explored the possibilities in combined therapies for eliminating difficult microbes. The rise of antibiotic resistant bacteria is a growing risk that antibiotics cannot mitigate. Instead, oxidation from PDT is proposed in combined therapies to provide a synergistic effect. Similarly, PDT is used as an oxidative model on isolated cells, but has not been considered for whole organism application, where holistic responses may be observed more relevant to the natural disease state. Isolated cellular effects and responses are valuable in defining individual mechanisms, but whole-body OS is more directly applicable to natural disease.

Throughout these studies, PDT is tested in bacteria, hydrogels, and fruit flies. Antibiotic resistant bacteria were given minute PDT doses with notable reductions in resistance, while excessively large doses in hydrogels show little change in the material’s mechanical properties. This comparison demonstrates safety in application for soft implant infection clearing. PDT is also applied as a disease model rather than a curative treatment. Long-term exposure in fruit flies is shown to drastically accelerate aging, decrease locomotor efficacy, and in the brain increases accumulation of tau protein, increases vacuole formation, and alters mechanical properties as assessed by Brillouin spectroscopy. These results suggest an organism-wide effect and relevance for study of OS-related disease. The selected studies showcase these applications, impact and innovation to the field, and the broad potential of PDT in research and medicine.