Photosensitizer Chemistry in Photodynamic Therapy

Photodynamic therapy (PDT) harnesses light-activated dyes, known as photosensitisers, to generate cytotoxic reactive oxygen species upon irradiation. Central to PDT efficacy is the precise tuning of photophysical and photochemical properties of these molecules, which include porphyrins, chlorins, phthalocyanines and related macrocycles. Synthetic modifications at the macrocycle periphery control solubility, cellular uptake and subcellular localisation, while core metalation can enhance intersystem crossing and singlet oxygen production. Formulation strategies—ranging from lipid-based carriers and liposomal encapsulation to semisolid gels—address issues of bioavailability and selective delivery to tumour or infection sites. Recent efforts concentrate on elevating singlet oxygen quantum yields, minimising dark toxicity and exploiting targeting motifs for both cancerous and microbial indications. Advances in antimicrobial PDT underscore its potential against multidrug-resistant pathogens, while innovations in formulation broaden clinical applicability. The global impact of optimised photosensitisers spans oncology, dermatology and infectious disease, underlining the interdisciplinary nature of photosensitiser chemistry in translating molecular design into therapeutic solutions.

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Photosensitizer Chemistry in Photodynamic Therapy publication trend

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Technical terms

Photosensitizer: A molecule that, upon absorption of light, transfers energy to molecular oxygen to produce reactive oxygen species.

Photodynamic Therapy (PDT): A treatment modality that combines a photosensitiser, light of defined wavelength and oxygen to induce targeted cell death.

Singlet Oxygen Quantum Yield: The efficiency with which an excited photosensitiser generates singlet oxygen, a key cytotoxic species in PDT.

Liposomal Formulation: A drug delivery system in which a photosensitiser is encapsulated within lipid bilayers to improve solubility and biodistribution.

Macrocycle: A large ring-shaped organic molecule—such as a porphyrin or phthalocyanine—often used as a scaffold for photosensitisers.

References

1. Advances and perspectives in use of semisolid formulations for photodynamic methods. European Journal of Pharmaceutics and Biopharmaceutics (2024).
2. Novel Short PEG Chain-Substituted Porphyrins: Synthesis, Photochemistry, and In Vitro Photodynamic Activity against Cancer Cells. International Journal of Molecular Sciences (2022).
3. Zinc(II), Palladium(II), and Metal-Free Phthalocyanines Bearing Nipagin-Functionalized Substituents against Candida auris and Selected Multidrug-Resistant Microbes. Pharmaceutics (2022).