Work

Halogen substituted 4-thio-2′-deoxyuridines as photosensitizers for the photodynamic therapy of prostate cancer. An in vitro study

Year: 2025

Type: article

Abstract: Photodynamic therapy (PDT) is a minimally invasive modality that employs a photosensitizer (PS) and light exposure source within the PS's optimal absorption range to induce selective cytotoxic effects. This study investigates 5′-bromo-4-thio-2′-deoxyuridine (BrSdU) and 5′-iodo-4-thio-2′-deoxyuridine (ISdU), both modified nucleoside (MN)-based photosensitizers. The presence of the sulfur atom in their thionucleoside structures shifts their maximum absorption to approximately 350 nm, enabling efficient activation under UVA irradiation and minimizing the inner filter effect observed with conventional halogenated nucleosides. MTT assays confirm that BrSdU and ISdU exhibit negligible dark cytotoxicity in PC3 prostate cancer cells. In contrast, clonogenic assays reveal that UVA irradiation of BrSdU/ISdU-labeled cells significantly enhances cell lethality. Mechanistic analysis demonstrates that the combined treatment induces (1) a decrease in viable cell population with a concomitant increase in early apoptotic cells, (2) G2/M phase cell cycle arrest, (3) elevated levels of DNA double-strand breaks compared to UVA-only controls, and (4) no significant alteration in intracellular reactive oxygen species (ROS) levels. These results suggest that BrSdU and ISdU function as effective UVA-activated photosensitizers, mediating DNA-targeted photodynamic damage through mechanisms largely independent of ROS generation, and hold promise for further development in targeted cancer therapies. • BrSdU and ISdU are effective UVA-activated photosensitizers. • MTT tests confirm that BrSdU/ISdU exhibit negligible dark cytotoxicity in PC3 cells. • Clonogenic assays reveal that UVA irradiation of labeled cells reduces survival. • Exposure of PC3 cells to BrSdU or ISdU, in combination with UVA induced G2/M arrest. • Exposure of PC3 cells to BrSdU or ISdU, in combination with UVA causes DSBs.

Source: Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy

DOI: 10.1016/j.saa.2025.126802

Authors: Anna Czaja, Magdalena Datta, Janusz Rak, Magdalena Zdrowowicz

Institution: University of Gdańsk

Language: English

Topic: Photodynamic Therapy Research Studies

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,750