Heavy Metal Chelation and Bioprotective Activity of Dextran-DOTA Macromolecular Conjugate

Abstract

Widespread exposure and bioaccumulation of toxic heavy metals have increased the incidence of metal poisoning, particularly in children. Although chelation therapy can remove toxic metals, current drugs are limited by toxicity and side effects, restricting treatment to severe cases. We report the synthesis of a water-soluble macromolecular chelator through esterification of dextran with tetraxetan (DOTA) to create a safer systemic chelator. Chemical characterization confirmed successful conjugation with a high degree of substitution. The resulting Dex-DOTA conjugate exhibited enhanced affinity for lead and cadmium, demonstrating the advantages of macromolecular architecture for metal selectivity and retention. Dex-DOTA also showed excellent colloidal stability, no cytotoxicity, and improved cell survival following metal exposure. In C. elegans, the conjugate was nontoxic and mitigated heavy metal-induced toxicity. These findings establish Dex-DOTA as a stable, selective, and biocompatible chelator with strong potential for safer systemic treatment of heavy metal poisoning.