Singlet Oxygen Chemistry and Applications in Photodynamic Therapy

Singlet oxygen (¹O₂) occupies a central role in photodynamic therapy (PDT) through its capacity to oxidise biological targets selectively upon activation of a photosensitiser by light. Generated via energy transfer from an excited photosensitiser to ground‐state molecular oxygen, ¹O₂ engages in highly selective reactions with cellular macromolecules, triggering lipid peroxidation, protein oxidation and DNA strand breaks. This type II photochemical pathway underpins the clinical efficacy of PDT in oncology, antimicrobial treatments and dermatological applications. Advances in sensitiser design have focused on optimising ¹O₂ quantum yields, tuning absorption into the therapeutic window (650–800 nm) and improving tumour selectivity. Concurrently, strategies to overcome intrinsic limitations—such as hypoxic tumour microenvironments, inefficient ¹O₂ diffusion and off‐target phototoxicity—have prompted the development of endoperoxide‐based reservoirs, hypoxia-tolerant nanocarriers and targeted delivery systems. Emerging work also emphasises precise quantification of in situ ¹O₂ using robust probes, enabling real-time dosimetry and mechanistic insight into photochemical and biological processes.

Research from Nature Portfolio

Recent studies have revealed that a widely used fluorescent probe for singlet oxygen detection can exhibit pronounced fluorescence under ionising radiation even when ¹O₂ is not produced. This finding uncovers a previously unrecognised source of artefact in common assay formats and highlights the need for more specific detection methods that avoid interference from reactive species generated by radiation, thereby refining both preclinical research and potential clinical monitoring of PDT efficacy.

Singlet Oxygen Chemistry and Applications in Photodynamic Therapy publication trend

The graph below shows the total number of articles in singlet oxygen chemistry and applications in photodynamic therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Singlet oxygen: the lowest electronically excited state of molecular oxygen, characterised by paired electron spins and high reactivity towards organic substrates.

Photosensitiser: a molecule that absorbs light and transfers its excited‐state energy to molecular oxygen, generating singlet oxygen.

Endoperoxide: a cyclic peroxide intermediate formed by the addition of singlet oxygen to a conjugated diene, capable of thermally releasing ¹O₂.

Hypoxia: a condition of reduced oxygen availability, commonly found in solid tumours, which limits conventional photodynamic oxygenation.

Proton-sponge effect: the ability of certain polymers to buffer protons in acidic compartments, causing osmotic swelling that facilitates endosomal escape.

Photodynamic therapy: a treatment modality combining light, photosensitisers and molecular oxygen to generate cytotoxic singlet oxygen in targeted tissues.

References

1. Singlet Oxygen Sensor Green is not a Suitable Probe for 1O2 in the Presence of Ionizing Radiation. Scientific Reports (2019).
2. Proton‐Driven Transformable 1O2‐Nanotrap for Dark and Hypoxia Tolerant Photodynamic Therapy. Advanced Science (2022).
3. Prostate-specific membrane antigen (PSMA) targeted singlet oxygen delivery via endoperoxide tethered ligands. Chemical Communications (2022).
4. A Classic Near-Infrared Probe Indocyanine Green for Detecting Singlet Oxygen. International Journal of Molecular Sciences (2016).