Bioorthogonal strategies for the in vivo synthesis or release of drugs

The site-specific delivery of antitumor agents is a rapidly developing field that relies on prodrug activation and uncaging strategies. For this purpose, a wide range of homogeneous and heterogeneous biocompatible activators/catalysts have been developed to convert caged drugs with low toxicity and high stability in physiological settings into active substances in a bioorthogonal manner. The current methods allow for the site-specific delivery of activators and prodrugs to organelles, target cells, or tumors in living organisms. Here, we present an overview of the latest advances in catalytic drugs, highlighting the expanding toolbox of bioorthogonal activation strategies made possible by transition metals acting as activators or catalysts.