Increasing time on target: utilization of inhibitors of cysteine cathepsins to enhance the tumor retention of receptor-targeted agents.

We report a strategy of utilizing irreversible cysteine cathepsin inhibitor as trapping agent to increase the tumor residence time of receptor-targeted agents. The targeted constructs incorporating these cysteine cathepsin trapping agents were able to form high molecular weight adducts with intracellular cysteine cathepsins, thus achieving superior retention in tumor tissues.