Recent advances in metal–drug self-assembled nanomedicines: Carrier-free strategies for multifunctional cancer therapy

Carrier-free nanomedicines constructed through metal–ligand coordination have emerged as a promising paradigm for cancer therapy, offering ultra-high drug loading, simplified formulation, and intrinsic responsiveness to tumor microenvironments. These assemblies exploit therapeutic molecules and metal ions as both structural and functional components, integrating catalytic activity, redox regulation, immune modulation, and imaging capability within a single supramolecular platform. This review summarizes recent progress in coordination-driven self-assembly, including the roles of phenolic, carboxylate, multidentate, and other ligand-bearing small molecules in generating stable, stimuli-responsive nanostructures. Particular emphasis is placed on the unique biological functions of representative metal ions for ferroptosis-/cuproptosis-inducing therapies, endoplasmic reticulum calcium flux-mediated apoptosis, cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signalling pathway-dependent immune activation, etc. Emerging strategies that incorporate multiple drugs or multiple metals into one carrier-free nanoparticle are also highlighted, enabling synergistic multimodal therapy and integrated diagnostics. Finally, we discuss current challenges and outline future opportunities for coordination-based carrier-free nanomedicines to advance precision oncology.