# Nanochelation Therapies for Iron Overload Disorders

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS LOWELL · 2020 · $643,608

## Abstract

PROJECT SUMMARY/ABSTRACT
Iron overload, best represented by hereditary hemochromatosis (primary/genetic iron overload) and
transfusional hemoglobinopathy (secondary/acquired iron overload), is a well-defined risk factor for several
critical diseases, including heart failure, liver cirrhosis, arthritis, diabetes and neurodegenerative diseases. Iron
chelators are clinically used to reduce iron burden, but the use of chelators is limited by a number of significant
side effects, including hypotension, tachycardia, agranulocytosis, neutropenia, ocular/auditory toxicities, loss of
essential nutrients, musculoskeletal-joint pains, gastrointestinal bleeding, hepatic fibrosis and renal failure.
Considering tens of millions of people affected by various types of iron overload disorders, there are urgent
needs for a new therapeutic strategy to minimize unwanted adverse effects of chelators by controlling the fate
of iron-chelator complex in the body. The hypothesis guiding this study is that iron chelators coated onto size-
and surface-modified nanoparticles (“nanochelators”) will collect excess iron from various body compartments,
and the iron-chelator-nanoparticle complexes will be exclusively cleared by two major excretion pathways: into
the urinary bladder by renal excretion and into the gallbladder/gut by biliary excretion depending on the size
and surface properties of nanoparticles. The specific aims of this study are focused on 1) developing
multifunctional chelator-coated urine-targeted nanoparticles (UNPs) to effectively harvest circulating and labile
iron and dispose the iron-UNP complex by urinary excretion, 2) engineering surface-modified, chelator-coated
bile-targeted nanoparticles (BNPs) to dispose excess iron exclusively by the biliary secretion pathway, 3)
characterizing the in vivo pharmacokinetics and pharmacodynamics of developed nanochelators in iron
disposal using clinically-relevant mouse and rat models of iron overload, and 4) evaluating the therapeutic
efficacy of nanochelators in the amelioration of physiological complications associated with iron overload
disorders. Overall, this strategy provides a safe and effective method with increased benefit/risk ratios of iron
chelators to support therapeutic benefits over numerous iron overload disorders by a combination of
nanotechnology and transgenic animal models of iron overload. Furthermore, the idea of “targeted clearance”
can be tested for the facilitated elimination of other toxic substances, such as heavy metals and drugs of
abuse, from the body. By addressing these questions, we hope to both identify novel therapeutic approaches
and improve clinical outcomes.

## Key facts

- **NIH application ID:** 10318332
- **Project number:** 7R01HL143020-04
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS LOWELL
- **Principal Investigator:** Hak Soo Choi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $643,608
- **Award type:** 7
- **Project period:** 2021-01-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318332

## Citation

> US National Institutes of Health, RePORTER application 10318332, Nanochelation Therapies for Iron Overload Disorders (7R01HL143020-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10318332. Licensed CC0.

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