In Situ Assembly of Active Therapeutics Through Albumin-Mediated Metal Transfer

Forming active therapeutic agents in situ can be a promising strategy to obtain safer and more effective treatments. However, achieving controlled formation of a drug in complex biological settings requires a detailed understanding of the target environment where the new therapeutic agent will be generated and the use of well-designed activation strategies. Here, we demonstrate that it is possible to form active metal complexes in blood serum and plasma by using ligands that target metal ions transported by albumin after they are bound to the protein. As a proof of concept, we applied this strategy to activate photosensitizers (PS) for photodynamic therapy (PDT). In situ metalation generated photoactivatable complexes with enhanced photochemical properties and anticancer activity, establishing albumin-bound metal ions as an endogenous resource for therapeutic activation.