Light-Enhanced Cytotoxicity of Doxorubicin by Photoactivation

Autor: Giulia Greco, Luca Ulfo, Eleonora Turrini, Alessia Marconi, Paolo Emidio Costantini, Tainah Dorina Marforio, Edoardo Jun Mattioli, Matteo Di Giosia, Alberto Danielli, Carmela Fimognari, Matteo Calvaresi
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cells, Vol 12, Iss 3, p 392 (2023)
Druh dokumentu: article
ISSN: 12030392
2073-4409
DOI: 10.3390/cells12030392
Popis: The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs. Despite its high efficacy, two factors limit its clinical use: severe side effects and the development of chemoresistance. Doxorubicin is a chromophore, able to absorb light in the visible range, making it a potential PS. Here, we exploited the intrinsic photosensitizing properties of doxorubicin to enhance its anticancer activity in leukemia, breast, and epidermoid carcinoma cells, upon irradiation. Light can selectively trigger the local generation of reactive oxygen species (ROS), following photophysical pathways. Doxorubicin showed a concentration-dependent ability to generate peroxides and singlet oxygen upon irradiation. The underlying mechanisms leading to the increase in its cytotoxic activity were intracellular ROS generation and the induction of necrotic cell death. The nuclear localization of doxorubicin represents an added value for its use as a PS. The use of doxorubicin in PCT, simultaneously acting as a chemotherapeutic agent and a PS, may allow (i) an increase in the anticancer effects of the drug, and (ii) a decrease in its dose, and thus, its dose-related adverse effects.
Databáze: Directory of Open Access Journals
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