Precise control of metal–ligand interactions: advanced chelation strategies for next-generation theranostic nanomedicine

The chelation chemistry of metal ions is essential for the development of superior biomaterials and sophisticated nanoplatforms in theranostic nanomedicine. Distinct from previous reviews focusing on isolated applications, this work establishes a "descriptor-to-function" design framework that connects intrinsic coordination parameters, including electron configuration, ligand denticity, and thermodynamic stability, which is directly related to the biological performance of nanomaterials. We systematically assess recent advancements across interconnected frontiers: the engineering of activatable and multimodal diagnostic imaging probes for high-contrast diagnosis; the targeted delivery of chelation-based chemotherapeutic and radiotherapeutic agents to enhance efficacy while mitigating toxicity; and coordination-driven self-assembly for constructing stimuli-responsive nanostructures. Furthermore, the review explores ion interference therapies utilizing selective chelation to disrupt disease mechanisms, alongside chelation-based biosensing platforms for high-sensitivity molecular detection. By elucidating the underlying structure-function relationships that dictate diagnostic and therapeutic efficiencies, we demonstrate how rational chelation strategies can overcome biological barriers. This mechanistic perspective offers a rational roadmap for developing next-generation intelligent biomaterials, ultimately accelerating the translation of chelation technologies from molecular design to clinical reality.