Metallacages for biomedical applications

Metallacages (MCgs) are assembled by forming coordination and organometallic bonds between multitopic ligands and metal nodes. The synthetically designed directionality of the ligands, combined with the well-defined coordination geometry of the metal ions, allows the creation of three-dimensional structures delimiting a cavity. Besides the host-guest chemistry arising from the formed cavity – capable of hosting small molecules and whose chemical character can be tuned by the design of the building blocks – metallacages can be modularly designed to include functional moieties.1

Our group aims to generate metallacages using photoactive building blocks applicable in the biomedical context, for that, with enhanced stability and functionality to improve their solubility, targeting and biodistribution are synthesized to further explore their bioactivity and applicability on sensing modalities. Our application of MCgs and drugs has shed light on the overlooked role of host-guest chemistry on drug-target interactions. In particular, we have observed remarkable selectivity of an MCg system by a guanine quadruplex (G4) – which are validated targets in cancer therapy – due to host-guest interactions; thus the investigation of the interaction of MCg structures with non-canonical DNA structures is also of our interest.2; Finally, we aim to exploit the multicomponent nature of metallacages to create multifunctional self-assembled platforms that integrate imaging and targeting capabilities for promising theranostic applications.3

 

Key publications

  1. Thomas, S. R.; Willnhammer, N.; Casini, A.; Moreno-Alcántar, G. Gold Metallacages: Design Principles and Applications. Chem 2025, 11 (6), 102502. https://doi.org/10.1016/j.chempr.2025.102502.
  2. Rodríguez-Prieto, T.; Wragg, D.; Heiduk, N.; Park, M.; Strittmatter, N.; Fischer, R. A.; Casini, A.; Moreno-Alcántar, G. A Golden Touch in the Design of Multifunctional Porphyrin Metallacages: Host–Guest Chemistry for Drug-Target Interactions. CCS Chem. 2024, 6 (7), 1662–1671. https://doi.org/10.31635/ccschem.024.202404056.
  3. Moreno-Alcántar, G.; Drexler, M.; Casini, A. Assembling a New Generation of Radiopharmaceuticals with Supramolecular Theranostics. Nat. Rev. Chem. 2024, 8 (12), 893–914. https://doi.org/10.1038/s41570-024-00657-4.