Recent advances in metallodrug: Coordination-induced synergy between clinically approved drugs and metal ions

Metallodrugs utilize metal ions as central elements in their structures to exploit unique properties such as coordination actions and redox activity for targeted biological interactions. They offer the advantage of high specificity in attacking diseased cells while minimizing damage to healthy tissues, which is vital in treatments such as chemotherapy. Recently, a new chemical approach in metallodrug has emerged, which is a coordination-induced synergy between clinically approved drugs and metal ions. The coordination of FDA-approved and clinically tested drugs with metal ions can form a drug-metal complex, which can further grow into drug-metal multiple-complexes and drug-metal nano-aggregates. As a next-generation drug repositioning, these complexes can provide unique and enhanced biological activities, with a high possibility for lab-to-market application. Drug-metal complexes are categorized into three main groups based on disease type and biological functions: (1) complexes for antimicrobial therapies, (2) complexes for anticancer therapies, and (3) complexes for new biological functions. This review aims to present an overview of recent advances in the therapeutic metallodrugs designed to understand the new biological functions. We hope that our summary, insights, and perspectives could contribute to future research and development in basic research and translational medicine. • Recent advances in metallodrugs from clinically approved drugs and metal ions are summarized. • A general overview of the design and synergetic bioactivity of metallodrugs is briefed. • Promising strategies and prospects for next-generation drug-metal complex materials are presented.