Double Targeting of Tumours with Pyrenyl-Modified Dendrimers Encapsulated in an Arene–Ruthenium Metallaprism

The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with <i>p</i>-cymene–ruthenium building blocks and 5,8-dioxido-1,4-naphthoquinonato (donq) bridges, in the presence of pyrenyl-containing dendrimers of different generations (P₀, P₁ and P₂), affords the triangular prismatic host–guest compounds [Pn⊂Ru₆(<i>p</i>-cymene)₆(tpt)₂(donq)₃]⁶⁺ ([Pn⊂<b>1</b>]⁶⁺). The host–guest nature of these systems, with the pyrenyl moiety being encapsulated in the hydrophobic cavity of the cage and the dendritic functional group pointing outwards, was confirmed by NMR spectroscopy (¹H, 2D and DOSY). The host–guest properties of these systems were studied in solution by NMR and UV/Vis spectroscopic methods, allowing the determination of their affinity constants (<i>K</i>_a). Moreover, the ability of these water-soluble host–guest systems to carry the pyrenyl-containing dendrimers into cancer cells was evaluated on human ovarian cancer cells. The host–guest systems are all more cytotoxic than the empty cage [<b>1</b>][CF₃SO₃]₆ (IC₅₀≈4 μM), with the most active compound, [P0⊂<b>1</b>][CF₃SO₃]₆, being an order of magnitude more cytotoxic.