Precise Control of Metal-Ligand Interactions: Advanced Chelation Strategies for Next-Generation Theranostic Nanomedicine

Abstract

The chelation chemistry of metal ions is essential for the development of superior biomaterials and sophisticated nanoplatforms in theranostic nanomedicine. This review offers an in-depth summary of recent advancements, focusing on the practical application of chelation-based strategies for precise regulation of metal-ligand interactions for various therapeutic purposes. We systematically assess their significant contributions across multiple interconnected topics: the engineering of activatable and multimodal diagnostic imaging probes that provide enhanced contrast and pathological specificity; the targeted delivery of chelation-based chemotherapeutic and radiotherapeutic agents, highlighting nanocarriers that improve drug efficacy while mitigating unexpected toxicity; selfassembly processes driven by coordination chemistry that facilitate the construction of stimuliresponsive nanostructures; ion interference therapies utilizing selective chelation to deplete or administer specific metal ions to disrupt fundamental disease mechanisms; and biosensing platforms based on chelation for high-sensitivity molecular detection. The review presents a "descriptor-tofunction" design strategy that connects intrinsic coordination parameters, including electron configuration, ligand denticity, and complex stability, to the resulting biological performance of nanomaterials. We elucidate the underlying structure-function relationships that dictate diagnostic and therapeutic efficiencies, asserting that rational design of chelation complexes and a profound mechanistic understanding of coordination chemistry are essential for overcoming biological barriers and achieving precise control over the biological behavior and therapeutic efficacy of nanomaterials.Future perspectives on alternative chelation reactions coupled with theranostic systems, as well as significant translational challenges, are outlined, highlighting prospects for interdisciplinary collaboration to tackle obstacles in clinical applications.