Coupling light-activated metal complexes for controlled drug release to antibodies can be utilized to target tumor-specific antigens, thereby decreasing systemic toxicity caused by non-specific drug distribution as well as decreasing the effective therapeutic dose required. Ru(II)-polypyridyl complexes are promising photochemotherapy (PCT) agents for drug delivery due to their efficient visible light absorption, tunable excited state properties, and accessible triplet ligand field (3LF) excited states that promote ligand dissociation. Previous studies indicate that 5-cyanouracil (5CNU), which inhibits pyrimidine catabolism in vivo, exhibits low toxicity when coordinated to a Ru(II)-polypyridyl complex in the dark and is released from [Ru(bpy)2(5CNU)2]2+ and [Ru(tpy)(5CNU)3]2+ (bpy = 2,2ʹ-bipyridine; tpy = 2,2ʹ:6ʹ,2ʹʹ-terpyridine) with visible light excitation, resulting in HeLa cell toxicity. Conjugation of related Ru(II)-polypyridyl complexes to antibodies to target a specific antigen is desired to produce a more selective drug delivery method, and this field is largely unexplored. Reported herein are strategies to covalently attach complexes of the [Ru(tpy)(NN)(drug)]2+ architecture, where NN is a bidentate ligand and the drug is a nitrile or pyridine-containing anticancer drug, to antibodies using dicyclohexyl carbodiimide (DCC) to form peptide bonds between the carboxylic acid substituents on either the tpy or NN ligands and the primary amines on the antibody. The photochemistry of drug release from the metal complex-antibody conjugates will be explored.

Ru(II) complex-antibody conjugation for targeted photochemotherapy

249th National Meeting (2015)

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