In vivo metallophilic self-assembly of a light-activated anticancer drug

Abstract Self-assembling molecular drugs combine the easy preparation typical of small-molecule chemotherapy and the tumor-targeting properties of drug-nanoparticle conjugates. However, they require a supramolecular interaction that survives the complex environment of a living animal. Here, we report that the metallophilic interaction between cyclometalated palladium complexes generates supramolecular nanostructures in living mice that have a long circulation time (above 12 h) and efficient tumor accumulation rate (up to 10.2% ID/g) in a skin melanoma tumor model. Green light activation leads to efficient tumor destruction due to the photodynamic effect generated by the self-assembled palladium complexes, as demonstrated in vitro by an up to >96-fold cytotoxicity increase upon irradiation. This work demonstrates that metallophilic interactions are well suited for generating stable supramolecular nanotherapeutics in vivo with exceptional tumor-targeting properties.