A Golden Touch in the Design of Multifunctional Porphyrin Metallacages: Host–Guest Chemistry for Drug-Target Interactions

The use of three-dimensional self-assembled metallacages (MCgs) as multimodal drug platforms holds great promise. However, the synthesis of MCgs with increased complexity and functionality is a great challenge since understanding of the interaction of MCgs with biological targets is still limited. In this context, this work reports on the integration of a gold(III) porphyrin scaffold into a prismatic MCg structure and explores its application for multimodal therapy of cancer in vitro, namely enabling both photodynamic therapy and chemotherapy. Combining experimental approaches with a state-of-the-art metadynamics theoretical study, we discovered that the gold cage shows unprecedented host–guest interaction-driven selective stabilization of guanine-quadruplex (G4) structures – validated anticancer drug targets – disclosing a new mechanism to pursue in the design of supramolecular drugs.