Self-Assembled Iron(III) Coordination Cage as an MRI-Active Carrier for a Gold(I) Drug

Abstract

A T₁ MRI probe based on a self-assembled coordination cage with four iron(III) centers acts as a host for the hydrolysis product of the gold(I) anticancer drug, Au(PEt₃)Cl. ¹H NMR characterization of the gold complex encapsulated within the diamagnetic Ga(III) analog of the coordination cage is consistent with loss of chloride to give aquated gold complex, most likely [Au(PEt₃)(OH₂)]⁺ within the cage. The gold complex undergoes pH-dependent speciation changes in the Ga(III) cage and is released at mildly acidic pH from both the Ga(III) and Fe(III) cages. NMR spectroscopy studies of the encapsulated gold complex in the presence of human serum albumin (HSA) show that the gold complex remains inside of the Ga(III) cage for several hours, resisting release and binding to cysteine residues of HSA. The Fe(III) cage with encapsulated gold complex shows enhanced contrast of the vasculature and uptake into CT26 tumors in BALB/c mice as shown by MRI. The gold complex is solubilized by the iron(III) cage for intravenous injection, whereas the free complex must be injected intraperitoneally. Gold complex accumulates in the tumor for both caged and free complex over 1–48 h as measured by ex-vivo analysis. Encapsulation in the Fe(III) cage modulates the biodistribution of the gold complex in mice in comparison to the free complex, consistent with the function of the cage as a carrier.