Synthesis of Eu, Sm and Dy metal-organic framework nanosheets based on pyridyl carboxylic acid and their cytotoxic mechanism in vitro

The rational design of Ln-MOF nanosheets (NSs) with tunable and ultrathin structure is promising in tumor therapy. A series of Ln-DPIA1–3 (Ln = Eu, Sm and Dy) MOF NSs were prepared by the hydrothermal method. Ln-DPIA1–3 MOF NSs were characterized by SC-XRD, PXRD, NMR, HRMS and FT-IR spectra, TG and EA. The morphology and element distribution of complexes was observed by SEM, TEM and EDS. The malignant biological behavior of Ln-DPIA1–3 MOF NSs against BxPC-3 cells was studied by MTT assay, flow cytometry and fluorescence imaging. Ln-DPIA1–3 MOF NSs exhibited moderate cytotoxicity against BxPC-3 cells, especially for Eu-DPIA with IC₅₀ value of 10.08 μg/mL. Cytotoxic mechanism of the complexes was investigated through competitive binding assay, DNA binding affinity determination, DNA cleavage and molecular docking analysis. In addition, ADME parameter for Ln-DPIA1–3 MOF NSs were simulated. As a result, the complexes inserted to DNA instead of EtBr and strengthened DNA cleavage. Moreover, the DNA binding constant for Eu-DPIA was highest among Ln-DPIA1–3 MOF NSs, and Eu-DPIA interacted with target DNA through multiple hydrogen bonds.