Antibody-drug conjugates (ADC) are a newly emerging therapy that combines a potent cytotoxic payload compound with an antibody to selectively deliver a cancer treatment. Once the ADC binds to the targeted antigen present on select cancer cells, the ADC undergoes endocytosis and the covalent linker is cleaved in lysosomes, releasing the cytotoxic payload and killing the cell. Due to premature cleavage of the payload and the inability to kill bystander cells in the cancer cells, the ADC platform has suffered from adverse side effects and resistance development. We postulated that a more modular drug delivery platform, where an antibody-metal catalyst conjugate unmasks a masked cytotoxic drug, would solve the issues with ADC therapies and would make the development process more affordable. Herein presented is our proof-of-concept study showing that albumin conjugated to a ruthenium catalyst retains the deallylation ability to unmask a masked dye compound under physiologically relevant conditions.

Protein metal catalyst conjugates for bio-orthogonal unmasking chemistry

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