Fındık Basak Koca, Lognon Elise, Catak Saron, Monari Antonio
Université Paris Cité and CNRS, ITODYS, 75006, Paris, France.
Department of Chemistry, Bogazici University, Bebek, 34342, Istanbul, Turkey.
Photochem Photobiol Sci. 2025 Jun 12. doi: 10.1007/s43630-025-00745-4.
Photodynamic Therapy (PDT), which involves the combined action of a drug and its activation by suitable light, is a particularly attractive novel cancer therapy method due to less systemic side effects. However, the delivery and accumulation of the PDT drug into cancer cells is still problematic. Here, by using μ-scale molecular dynamic simulations combined with quantum mechanics/molecular mechanics approaches, we examine the behavior of a PDT drug functionalized with a folic acid unit targeting the folate receptor α (FR-α), which is overexpressed in ovarian cancer cells. We show that the PDT drug forms a stable complex with the folate receptor, albeit slightly disrupting the main interaction patterns as compared to the parent folate ligand. Furthermore, we also show that the optical properties of the PDT drug are not altered by its interaction with the protein. Our results confirm that coupling with folate is an attractive strategy for selective active delivery of PDT agents.
光动力疗法（PDT）涉及药物及其通过适当光激活的联合作用，由于全身副作用较小，它是一种特别有吸引力的新型癌症治疗方法。然而，PDT药物向癌细胞的递送和积累仍然存在问题。在这里，通过使用微尺度分子动力学模拟结合量子力学/分子力学方法，我们研究了一种用叶酸单元功能化的PDT药物的行为，该叶酸单元靶向在卵巢癌细胞中过表达的叶酸受体α（FR-α）。我们表明，PDT药物与叶酸受体形成稳定的复合物，尽管与母体叶酸配体相比，它略微破坏了主要的相互作用模式。此外，我们还表明，PDT药物的光学性质不会因其与蛋白质的相互作用而改变。我们的结果证实，与叶酸偶联是一种有吸引力的策略，用于选择性主动递送PDT药物。
