Metal-directed nanomedicines for imaging-guided disease treatment

Metal-directed self-assembly, driven by metal-ligand coordination, represents a highly versatile and efficient strategy for constructing drug delivery systems with precisely tunable properties, inherent imaging capabilities, and broad biomedical applications. Stimuli-responsive metal-directed drug delivery systems (MDDSs), guided by advanced imaging techniques, enable precise control over their size and spatial architecture while facilitating site-specific drug release. Moreover, certain metal ions play a dual role, not only orchestrating the self-assembly process but also serving as therapeutic agents and regulatory components for the treatment of various diseases, including cancer, microbial infections, and Alzheimer's disease. This review provides a comprehensive overview of the self-assembly mechanisms underlying diverse MDDSs and their applications in image-guided therapy. Furthermore, we critically examine existing challenges in the field and propose strategic directions to propel the advancement of metal-directed self-assembly in drug delivery. Given the profound implications of this research, further exploration of the critical roles of metal coordination in self-assembly is imperative for the development of next-generation drug delivery platforms. STATEMENT OF SIGNIFICANCE: This review systematically summarize the self-assembly mechanisms of metal-directed drug delivery systems, outlines their applications in image-guided therapy and discusses the current challenges that remain. Furthermore, it elucidates the unique regulatory roles of metal ions in precise drug release and multimodal therapy, providing valuable insights and broad appeal for the development and clinical translation of next-generation smart nanomedicine platforms.