Development of Deferoxamine‐Functionalized Cyclodextrin Polymer for Targeted Iron Chelation

TL;DR

A new polymer with deferoxamine units is developed to improve iron chelation therapy with reduced toxicity.

Contribution

A cyclodextrin polymer functionalized with multiple deferoxamine units is introduced for targeted iron chelation.

Findings

The polymer shows equal complexing capacity to free deferoxamine but lower cytotoxicity in cancer cell lines.

The conjugate exhibits significantly reduced antiproliferative activity compared to free deferoxamine.

The polymer may offer a promising strategy for improving iron chelation therapies.

Abstract

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.

The cyclodextrin polymer is conjugated with 35 deferoxamine units and can form iron(III) complexes. The polymer exhibits significantly lower antiproliferative activity than free deferoxamine. The cyclodextrin polymer with multiple deferoxamine units may present a promising strategy for improving the efficacy of iron chelation therapies.© 2025 WILEY‐VCH GmbH

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