Design of Polymer Metal Complexes: The Utility of Polymer Architectures on Advanced Biomaterial Performances

ABSTRACT Metal complexes are utilized in numerous medical and biological applications. However, their direct use as small‐molecule agents is often challenging due to rapid systemic clearance, unfavorable biodistribution, and loss of catalytic efficacy under the diluted conditions of a biological milieu. Incorporating the metal complexes into a polymer addresses these issues, providing three key advantages. First, it significantly improves pharmacokinetics by leveraging the size, which leads to a prolonged circulation and an enhanced therapeutic index for systemically administered medicines. Second, the polymer matrix creates a locally concentrated environment for the metal complexes. Neighboring metal complexes allow for efficient reactions, such as the generation of reactive oxygen species, even under biologically dilute conditions. Third, the multivalent effect of multiple binding sites on the polymer chain dramatically increases molecular recognition and binding affinity. This can be the driving force for supramolecular formation, including nanoparticles and hydrogels. Combining these merits could advance a new generation of biomaterials, enabling various types of theranostics. The polymer matrix also promotes catalytic reactions of metal complexes that cannot feasibly proceed in an ordinary aqueous solution state, mirroring a biological system. Thus, we believe that polymer‐metal complexes will further promote biomaterial development, including in medicines and artificial tissues.