DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex

The sgc8c aptamer is a 41-base DNA oligonucleotide that binds to leukaemia cells with high affinity and specificity. In this work we examined the utility of this aptamer as both a delivery vehicle and an active targeting agent for an inert platinum complex [(1,10-phenathroline)(ethylenediamine)platinum(II)]2+. The aptamer forms a stem-and-loop confirmation as determined by circular dichroism. This conformation is adopted in both water and phosphate buffered saline solutions. The metal complex binds through intercalation into the aptamer's double helical stem with a binding constant of approximately 4.3×104M−1. Binding of the metal complex to the aptamer had a significant effect on the aptamer's global conformation, and increased its melting temperature by 28°C possibly through lengthening and stiffening of the aptamer stem. The effect of the aptamer on the metal complex's cytotoxicity and cellular uptake was determined using in vitro assays with the target leukaemia cell line CCRF-CEM and the off-target ovarian cancer cell lines A2780 and A2780cp70. The aptamer has little inherent cytotoxicity and when used to deliver the metal complex results in a significant decrease in the metal complex's cytotoxicity and uptake. The reason(s) for the poor uptake and activity may be due to the change in aptamer conformation which affects its ability to recognise leukaemia cells. The sgc8c aptamer forms a stem-and-loop type conformation into which the platinum(II) complex PHENEN can intercalate, but results in reduced metal complex cytotoxicity and uptake. [Display omitted] •The sgc8c aptamer forms a stem-and-loop structure.•The 1,10-phenanthroline based platinum complex PHENEN binds via an intercalation mode.•Binding of the PHENEN to sgc8c aptamer locks the aptamer's conformation causing the aptamer to lose its ability to recognise its target: leukaemia cells.