Biomedical applications of multinuclear Pt(II)/Ru(II)/Ir(III) metallo-supramolecular assemblies for intensive cancer therapy

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 expected that this review will afford important guidance for the further development of these promising anticancer agents in biological applications, resulting in innovative anticancer agents that continue along this already promising path.