Nonspecific cellular and tissue components during photodynamic therapy

Nonspecific cellular and tissue components during photodynamic therapy (PDT) refer to the diverse biological substrates—including lipids, proteins, and organelles—that are oxidatively damaged by reactive oxygen species (ROS) generated during treatment (Agostinis et al., 2011). Unlike traditional targeted therapies that bind to specific receptors or enzymes, PDT relies on the localization of a photosensitizer within tissues and its subsequent activation by light. The resulting ROS, particularly singlet oxygen, have an extremely short half-life and diffusion radius, causing irreversible damage to the mitochondria, lysosomes, and plasma membranes of cells in the immediate vicinity of the photosensitizer (Castano et al., 2004). This process triggers multiple pathways of cell death, such as apoptosis and necrosis, while simultaneously damaging the tumor vasculature and stimulating a localized inflammatory immune response (National Cancer Institute, 2021). Consequently, the therapeutic 'target' is not a single molecule but rather the entire cellular environment where the photosensitizer has accumulated and light is applied.

Other names

Cellular substrates of photodynamic therapyPDT targetsIntracellular organelles in PDTTumor microenvironment components in PDTNonspecific oxidative targets

Photosensitizers accumulate in target tissues and, upon activation by specific wavelengths of light, undergo photochemical reactions (Type I or Type II) to produce reactive oxygen species (ROS), such as singlet oxygen. These ROS cause nonspecific oxidative damage to nearby cellular membranes, proteins, and organelles, leading to localized tissue destruction (Agostinis et al., 2011; National Cancer Institute, 2021).