DNA-binding, cytotoxicity and apoptosis induction of Pt/Fe-based heterometallo-supramolecular polymer for anticancer drug application

摘要

We synthesized two Pt/Fe-based metallo-supramolecular polymers with Pt (II) and Fe(II) introduced alternately (polyFePtL1 and polyFePtL2) for anticancer drug application. They have octahedral Fe(II)-centers and square-planar Pt (II)-centers bound with acetylide TPY (4-ethynyl-(2,2':6',2 ''-terpyridine) and -PEt3 (polyFePtL1) or -PPh3 (polyFePtL2). We measured their binding affinity to calf-thymus DNA (ct-DNA) by the UV-vis spectral titration. The binding constant of polyFePtL2 (K-b = 6.0 x 10(7) M-1) is 15-fold higher than that of polyFePtL1 (K-b = 4.0 x 10(6) M-1). The high binding affinity of polyFePtL2 indicates the intercalative binding of the -PPh3 moieties to DNA in addition to the groove binding of the polymer to DNA. They showed high cytotoxicity against human lung cancer cell line (A549). PolyFePtL2 has almost twice higher cytotoxicity (41% viable cell) than polyFePtL1 in 10 mu M concentration. We also inspected the cell apoptosis mechanism by FACS using Annexin-V FITC/PI double staining assay and found that polyFePtL2 induced apoptosis selectively leading to cancer cell death with similar to 15% detectable apoptotic cell. (C) 2019 Published by Elsevier B.V.