Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum-Università di Bologna,40126 Bologna, Italy.
Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum-Università di Bologna, 40126 Bologna, Italy.
Cells. 2023 Jan 21;12(3):392. doi: 10.3390/cells12030392.
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.
光动力疗法与化疗（光化学疗法，PCT）的联合应用可导致附加或协同的抗肿瘤作用。通常，在 PCT 中使用两种不同的分子，即光敏剂（PS）和化疗药物。阿霉素是最成功的化疗药物之一。尽管其疗效高，但有两个因素限制了其临床应用：严重的副作用和耐药性的发展。阿霉素是一种生色团，能够在可见光范围内吸收光，使其成为一种潜在的 PS。在这里，我们利用阿霉素的固有光敏特性，在照射下增强其在白血病、乳腺癌和表皮样癌细胞中的抗癌活性。光可以通过光物理途径选择性地触发局部活性氧（ROS）的生成。阿霉素显示出在照射下生成过氧化物和单线态氧的浓度依赖性能力。导致其细胞毒性活性增加的潜在机制是细胞内 ROS 的产生和坏死细胞死亡的诱导。阿霉素的核定位为其作为 PS 的使用提供了附加值。将阿霉素用于 PCT 中，同时作为化疗药物和 PS 发挥作用，可能会（i）增加药物的抗癌效果，和（ii）减少其剂量，从而减少其剂量相关的不良反应。
