Coordination chemistry-enabled drug delivery systems: metal-ligand platforms for controlled release and targeted...

Coordination chemistry presents an ideal molecular platform for the development of superior drug-delivery systems that can be effectively released, selectively targeted, and integrated into functional therapeutic systems. Due to their predictable geometries and tunable bonding properties, metal ions can form a variety of structures, including coordination polymer nanoparticles (CPNs), metal-organic frameworks (MOFs), supramolecular coordination complexes (SCCs), and metal-ligand cross-linked hydrogels. These structures possess a high cargo-loading ability and are sensitive to physiologically significant stimuli, including pH gradients, redox imbalances, enzymatic activity, and light. In addition to drug encapsulation, metal centers are intrinsically imaging-contrastive, catalytic, magnetically responsive, and phototherapeutic, enabling synergistic, multimodal therapies. This review critically analyzes the principles of coordination underlying the rational design of these delivery platforms, the key classes of coordination-based carriers, and their applications in cancer therapy, antimicrobial and antiviral treatment, gene and protein delivery, and theranostics. Emerging trends, such as hybrid organic-inorganic-bimolecular systems, hierarchical self-assembly, and AI-directed design, have also been described as definite areas of transformation in next-generation therapeutics. Issues related to physiological stability, metal toxicity, immune response, and scalable manufacturing are discussed, along with means to support clinical translation. Coordination-based architectures are expected to give the next generation of precise therapeutics that facilitate spectacular regulation of molecular assembly, dynamic reactions, and treatment.