The Chemistry of Deception: Exploiting Tumor Hypoxia With Cobalt Prodrugs

Advancements in drug delivery systems have transformed therapeutic strategies by enabling site‐specific, controlled release of active agents—minimizing systemic toxicity and enhancing clinical outcomes. Among trace elements, cobalt has emerged as a promising candidate for drug carrier design due to the biological compatibility of its redox behavior. In solid tumors, hypoxia is a defining pathological feature that contributes to resistance against conventional chemotherapeutics. Co(III) complexes exhibit reduction potentials that align with hypoxic conditions, allowing selective activation and release of cytotoxic moieties within the tumor microenvironment. This redox‐triggered mechanism offers a targeted approach, improving drug efficacy while sparing healthy tissues. This review consolidates current insights into Co(III)‐based hypoxia‐activated prodrugs, emphasizing their design principles, activation pathways, and therapeutic relevance.