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In Silico Study of Active Delivery of a Photodynamic Therapy Drug Targeting the Folate Receptor

Koca-Findik, B.; Lognon, E.; Catak, S.; MONARI, A.

2025-03-19 biophysics
10.1101/2025.03.19.644100 bioRxiv
Show abstract

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 -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 (FR-), 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.

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