Self-Assembled\nIron(III) Coordination Cage as an MRI-Active\nCarrier for a Gold(I) Drug

A T<sub>1</sub> MRI probe based on a self-assembled coordination\ncage with four iron(III) centers acts as a host for the hydrolysis\nproduct of the gold(I) anticancer drug, Au(PEt<sub>3</sub>)Cl. <sup>1</sup>H NMR characterization of the gold complex encapsulated within\nthe diamagnetic Ga(III) analog of the coordination cage is consistent\nwith loss of chloride to give aquated gold complex, most likely [Au(PEt<sub>3</sub>)(OH<sub>2</sub>)]<sup>+</sup> within the cage. The gold complex\nundergoes pH-dependent speciation changes in the Ga(III) cage and\nis released at mildly acidic pH from both the Ga(III) and Fe(III)\ncages. NMR spectroscopy studies of the encapsulated gold complex in\nthe presence of human serum albumin (HSA) show that the gold complex\nremains inside of the Ga(III) cage for several hours, resisting release\nand binding to cysteine residues of HSA. The Fe(III) cage with encapsulated\ngold complex shows enhanced contrast of the vasculature and uptake\ninto CT26 tumors in BALB/c mice as shown by MRI. The gold complex\nis solubilized by the iron(III) cage for intravenous injection, whereas\nthe free complex must be injected intraperitoneally. Gold complex\naccumulates in the tumor for both caged and free complex over 1–48\nh as measured by ex-vivo analysis. Encapsulation in the Fe(III) cage\nmodulates the biodistribution of the gold complex in mice in comparison\nto the free complex, consistent with the function of the cage as a\ncarrier.