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Metal ions are essential elements in biological processes and immune homeostasis. They can regulate cancer cell death through multiple distinct molecular pathways and stimulate immune cells implicated in antitumor immune responses, suggesting opportunities to design novel metal ion-based cancer therapies. However, their small size and high charge density result in poor target cell uptake, uncontrolled biodistribution, and rapid clearance from the body, reducing therapeutic efficacy and increasing potential off-target toxicity. Metal coordination polymer nanoparticles (MCP NPs) are nanoscale polymer networks composed of metal ions and organic ligands linked via noncovalent coordination interactions. MCP NPs offer a promising nanoplatform for reshaping metal ions into more drug-like formulations, improving their in vivo pharmacological performance and therapeutic index for cancer therapy applications. This review provides a comprehensive overview of the inherent biological functions of metal ions in cancer therapy, showcasing examples of MCP NP systems designed for preclinical cancer therapy applications where drug delivery principles play a critical role in enhancing therapeutic outcomes. MCP NPs offer versatile metal ion engineering approaches using selected metal ions, various organic ligands, and functional payloads, enabling on-demand nano-drug designs that can significantly improve therapeutic efficacy and reduce side effects for effective cancer therapy.
Zhang et al. (Thu,) studied this question.