Intracellular molecular oxygen and biomolecular substrates

Intracellular molecular oxygen and biomolecular substrates represent the fundamental reactants in oxidative therapeutic modalities, most notably photodynamic therapy (PDT). In these applications, a pharmacological agent (photosensitizer) is localized within target tissues and activated by specific wavelengths of light. The activated photosensitizer interacts with ground-state molecular oxygen to produce highly reactive singlet oxygen or free radicals (Agostinis et al., 2011, CA Cancer J Clin). These reactive species then cause irreversible oxidative damage to various biomolecular substrates, including membrane lipids, structural proteins, and nucleic acids (Castano et al., 2004, Photodiagnosis Photodyn Ther). This cascade ultimately triggers cell death via apoptosis, necrosis, or autophagy, and can also induce localized vascular occlusion and an immune response against the treated tissue. While effective for localized malignancies and certain ophthalmic conditions, the efficacy of this approach is strictly dependent on the presence of sufficient intracellular oxygen levels and the proximity of the photosensitizer to vital cellular substrates (National Cancer Institute). Consequently, these entities are the functional targets of the photochemical reactions that drive the clinical utility of photosensitizers in treating cancer, macular degeneration, and certain infections (StatPearls).

Other names

Molecular oxygenO2Cellular substratesEndogenous oxygenPDT targets

Photosensitizers absorb light energy and transfer it to intracellular molecular oxygen to generate singlet oxygen or other reactive oxygen species (ROS), which subsequently oxidize and damage nearby biomolecular substrates (lipids, proteins, and nucleic acids), leading to cell death.