Mechanisms in photodynamic therapy: part one—photosensitizers, photochemistry and cellular localization

Abstract

SummaryThe use of non-toxic dyes or photosensitizers (PS) in combination with harmless visible light that is known as photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as a tumor therapy, some of its most successful applications are for non-malignant disease. In a series of three reviews we will discuss the mechanisms that operate in the field of PDT. Part one discusses the recent explosion in discovery and chemical synthesis of new PS. Some guidelines on how to choose an ideal PS for a particular application are presented. The photochemistry and photophysics of PS and the two pathways known as Type I (radicals and reactive oxygen species) and Type II (singlet oxygen) photochemical processes are discussed. To carry out PDT effectively in vivo, it is necessary to ensure sufficient light reaches all the diseased tissue. This involves understanding how light travels within various tissues and the relative effects of absorption and scattering. The fact that most of the PS are also fluorescent allows various optical imaging and monitoring strategies to be combined with PDT. The most important factor governing the outcome of PDT is how the PS interacts with cells in the target tissue or tumor, and the key aspect of this interaction is the subcellular localization of the PS. Examples of PS that localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes are given. Finally the use of 5-aminolevulinic acid as a natural precursor of the heme biosynthetic pathway, stimulates accumulation of the PS protoporphyrin IX is described.

Repeated exposures to blue light-activated eosin Y enhance inactivation of E. faecalis biofilms, in vitro

“…Also, a longer irradiation time may have accelerated photobleaching of the photosensitizer, which was shown to occur with irradiation times longer than 15 min [33]. Photobleaching is likely to happen when singlet oxygen or other ROS produced upon illumination reacts with the photosensitizer itself thereby reducing its availability for further photosensitization [34]. There is also evidence showing that high radiant exposures may cause oxygen depletion in the culture medium which consequently weakens the therapeutic effect [35].…”

Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

“…PDT is based on the delivery of photosensitizer drugs (PSs) to biological targets, which are then irradiated with light at specific wavelengths (3). There are many different kinds of PS, each one with its specific excitation wavelength.…”

“…During PS photoactivation, an excitable electron is promoted to a higher energy level (antibonding orbital) and the PS reaches the first excited singlet state. This excited state decays to a lower energy level by emitting fluorescence or, alternatively, it decays by the process of intersystem crossing to a state named triplet (3). This triplet state is long lived and, because of this feature, it is able to react with triplet oxygen molecules and other biomolecules or to emit phosphorescence (3).…”

“…This excited state decays to a lower energy level by emitting fluorescence or, alternatively, it decays by the process of intersystem crossing to a state named triplet (3). This triplet state is long lived and, because of this feature, it is able to react with triplet oxygen molecules and other biomolecules or to emit phosphorescence (3). When it transfers energy to triplet oxygen, very reactive species called singlet oxygen are produced.…”

“…PSs are classified as 1st, 2nd, and 3rd generation, or according to their respective chemical class (e.g., phenotiazine, porphyrins, chlorins, phthalocyanines) (3,5). Despite their effectiveness on tumor cells, the majority of these PSs have shown limitations to their use in clinical applications, which include extended retention in the host organism, substantial skin phototoxicity, low solubility in physiological solutions, low selective accumulation in the diseased tissue, and inappropriate half-lives within tissue, impairing the optimization of illumination schedules (6).…”