Biomedical Applications of Multinuclear Pt(II)/Ru(II)/Ir(III) Metallo- Supramolecular Assemblies for Intensive Cancer Therapy

•Supramolecular multinuclear Pt(II)/Ru(II)/Ir(III) coordination assemblies with almost limitless modularity and tunability offer great structural designability for creative novel complicated metallodrugs with nonclassical action modes.•The innovative Pt(II)/Ru(II)/Ir(III)-based supramolecular assemblies as integrated “circuits” implanted both characteristics of metal ions and organic ligands that could induce superior chemotherapeutic, phototherapeutic, or imaging abilities for intensive cancer therapy.•The comprehensive discussion between regulatory factors of structure design and cancer therapy, and positive perspectives will afford important guidance on the further development of biological applications, and motivate mutual understanding between synthetic chemists and biologists with the continuing help of specialists in photochemistry, pharmacology, bioimaging, etc. The development of highly efficient and minimally toxic agents with targeting abilities toward tumor tissues is an ongoing area of research in the fight against cancer. Different from the mononuclear and multinuclear metallodrug complexes, impressively, the unique supramolecular coordination complexes (SCCs) have shown great superiority in cancer treatment. The vast combinational flexibility of ligands and metal ions offers limitless opportunities to form desired SCCs, thus endows them with distinct, captivating and integrated biological and chemical properties. Compared to organic drugs that are predominantly one-dimensional (1D) or two-dimensional (2D) in shape, the structurally much more complicated three-dimensional (3D) multinuclear assemblies with elaborate sizes, shapes, or cavities can exhibit unexpected binding sensitivity and selectivity toward biomolecules. Over the last decades, significant progress has been made in the design and synthesis of novel SCCs for intensive cancer therapy. These assemblies have been formulated using new strategies and formulations, resulting in nonclassical action modes that show promising results. This review aims at gathering innovative multinuclear Pt(II), Ru(II), and Ir(III)-based metallo-assemblies as promising anticancer drugs. Each section is divided into different parts based on the number of metal ions and shapes of the assembly. Furthermore, the review concludes with an exploration of the regulatory factors of structure design and discusses the perspectives for the practical impact of this type of research in medicinal chemistry. It is expec