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General cellular biomolecules, encompassing lipids, proteins, and nucleic acids, function as the primary substrates for oxidative damage induced by singlet oxygen and other reactive oxygen species (ROS). This interaction is the fundamental principle behind photodynamic therapy (PDT), where a photosensitizing drug is activated by light to produce cytotoxic oxygen species in situ [1]. Singlet oxygen specifically reacts with electron-rich moieties, such as the imidazole ring of histidine or the double bonds in unsaturated fatty acids, leading to membrane disruption and protein inactivation [2, 3]. In nucleic acids, guanine bases are particularly susceptible to oxidation, which can result in mutagenic lesions or DNA strand breaks [4]. The cumulative damage to these diverse biomolecules triggers various cell death pathways, including apoptosis and necrosis, which is utilized clinically to treat solid tumors, actinic keratosis, and age-related macular degeneration [1, 5]. Because the damage is non-specific and localized to the area of light illumination, therapeutic selectivity is achieved through controlled light delivery rather than molecular binding specificity [1].
Generation of singlet oxygen and reactive oxygen species leading to non-specific oxidative degradation of cellular components [1, 2, 3]
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