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

IF 5.9 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2026-09-14 Epub Date: 2026-08-12 DOI:10.1021/acs.biomac.6c00847

Sebastian Guajardo, Hunter Wood, Chenyun Deng, Neo Alpha, Stefanie A. Sydlik

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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.

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右旋糖酐- dota大分子缀合物的重金属螯合及生物保护活性

有毒重金属的广泛接触和生物积累增加了金属中毒的发生率，特别是在儿童中。虽然螯合治疗可以去除有毒金属，但目前的药物受毒性和副作用的限制，限制了对重症病例的治疗。我们报道了一种水溶性大分子螯合剂的合成，通过右旋糖酐与四乙基糖（DOTA）的酯化反应来创造一种更安全的全身螯合剂。化学表征证实了高取代度的成功偶联。所得到的dex - dota偶联物对铅和镉的亲和力增强，证明了大分子结构在金属选择性和保留方面的优势。Dex-DOTA还显示出优异的胶体稳定性，无细胞毒性，并改善金属暴露后的细胞存活率。在秀丽隐杆线虫中，该偶联物无毒，减轻了重金属诱导的毒性。这些发现表明Dex-DOTA是一种稳定、选择性和生物相容性的螯合剂，具有更安全的全身重金属中毒治疗的强大潜力。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.