Development of Deferoxamine‐Functionalized Cyclodextrin Polymer for Targeted Iron Chelation

Polymeric systems are used in clinical settings to bind small molecules and ions. They show advantages in pharmacokinetics and reduced side effects compared to low-molecular-weight agents. In this study, a cross-linked β-cyclodextrin polymer is functionalized with deferoxamine to develop more efficient ways of delivering iron chelators. Deferoxamine is a well-known iron chelator used to treat iron overload conditions. The resulting deferoxamine polymeric conjugate, with an equal complexing capacity to deferoxamine, showed significantly lower cytotoxicity compared to free deferoxamine in all cancer cell lines studied (neuroblastoma SHSY5Y, breast cancer MDA-MB-231, ovarian adenocarcinoma A2780, and lung cancer A549). The results demonstrate that the conjugation reduces the toxicity of deferoxamine at the same complexing capacity and reveals the potential of deferoxamine-based cyclodextrin conjugates as a novel approach for targeting iron dyshomeostasis.