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Bacterial and local cellular macromolecules represent the broad array of biological substrates targeted by reactive oxygen species (ROS) during antimicrobial photodynamic therapy (aPDT) (Cieplik et al., 2018, https://doi.org/10.1016/j.pdpdt.2018.05.002). In this process, a photosensitizing agent is localized within or near the target microbes and subsequently activated by light of a specific wavelength (Wainwright et al., 2017, https://doi.org/10.1016/S1473-3099(16)30268-3). This activation triggers the production of highly reactive species, such as singlet oxygen and hydroxyl radicals, which induce oxidative stress (Hamblin, 2016, https://doi.org/10.1515/nanoph-2016-0012). These ROS non-specifically attack vital components including membrane lipids, structural and functional proteins, and genomic DNA or RNA, leading to rapid microbial inactivation (Cieplik et al., 2018). While primarily intended to eradicate pathogens, the non-discriminatory nature of ROS means that adjacent host cellular macromolecules can also be oxidized, which is a key consideration in clinical application (Hamblin, 2016). This multi-target mechanism is particularly advantageous for overcoming antibiotic resistance, as it is difficult for microbes to develop protective measures against such widespread oxidative damage (Wainwright et al., 2017).
Generation of reactive oxygen species (ROS) upon light activation of a photosensitizer, leading to non-specific oxidative damage and cell death.
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