Iron Chelation Therapy in Metal Overload Disorders

Iron chelation therapy constitutes a vital intervention for a range of disorders characterised by excess body iron, including transfusion‐dependent anaemias and hereditary haemochromatosis. By employing small molecules or engineered carriers that tightly bind free iron, chelation mitigates the generation of reactive oxygen species and prevents deposition of labile iron in vital organs. Conventional chelators such as deferoxamine, deferiprone and deferasirox differ in route of administration, half‐life and tissue penetration, with trade-offs between efficacy and toxicity. Recent advances focus on improving pharmacokinetic profiles, enhancing cell or organ specificity and overcoming barriers to central nervous system delivery. Nanoparticulate systems, polymeric conjugates and intranasal formulations have emerged to extend circulation time, reduce off-target effects and facilitate access across the blood–brain barrier. Together these innovations aim to improve patient compliance, broaden therapeutic scope to neurodegenerative and hepatic complications, and deliver safer, more effective management of iron and other metal overload states worldwide.

Research from Nature Portfolio

One foundational advance introduced renal clearable nanochelators that combine high-affinity iron binding with rapid kidney excretion. These nanoscale constructs display kidney‐specific biodistribution, enhance urinary iron removal more efficiently than conventional deferoxamine and reduce nephrotoxicity in animal models of iron overload. Subcutaneous dosing further improved pharmacodynamic profiles, leading to substantial reductions in serum and hepatic iron. A complementary strategy employed oxidation-sensitive nanogels incorporating deferoxamine within a degradable scaffold. These nanogels respond to elevated oxidative stress by fragmenting into active chelating units, modulating intracellular ferritin levels and maintaining iron homeostasis in overloaded cells while minimising cytotoxicity of the free chelator.

Iron Chelation Therapy in Metal Overload Disorders publication trend

The graph below shows the total number of articles in iron chelation therapy in metal overload disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Chelation therapy: A treatment method using ligands that form stable complexes with metal ions to facilitate their removal from the body.

Deferoxamine: A prototypical high-affinity iron chelator administered mainly by infusion, used to treat transfusional iron overload.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can damage lipids, proteins and DNA when unregulated.

Pharmacokinetics: The study of drug absorption, distribution, metabolism and excretion over time within an organism.

Pharmacodynamics: The investigation of the biochemical and physiological effects of a drug and its mechanism of action.

Blood–brain barrier: A selective endothelial interface that restricts passage of most compounds from the bloodstream into the central nervous system.

Nanochelator: A nanoscale delivery system engineered to carry chelating agents, enhancing targeting, release profile and safety.

Ferritin: An intracellular protein that stores iron in a non-toxic, bioavailable form and releases it in a regulated manner.

References

1. Renal clearable nanochelators for iron overload therapy. Nature Communications (2019).
2. Oxidation-Induced Degradable Nanogels for Iron Chelation. Scientific Reports (2016).
3. A Water-Soluble Chitosan Derivative for the Release of Bioactive Deferoxamine. International Journal of Molecular Sciences (2024).
4. Genetic Targets and Applications of Iron Chelators for Neurodegeneration with Brain Iron Accumulation. ACS Bio & Med Chem Au (2024).
5. Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease. Pharmaceuticals (2021).