从小的去铁酮到大分子胶束：自组装增强铁螯合。

From small deferiprone to macromolecular micelles: Self-assembly enhances iron chelation.

机构信息

School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, China.

College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China.

出版信息

J Colloid Interface Sci. 2019 Jan 1;533:375-384. doi: 10.1016/j.jcis.2018.08.086. Epub 2018 Aug 25.

DOI:10.1016/j.jcis.2018.08.086

PMID:30172148

Abstract

We report a self-assembly-based approach for improved iron chelation of small chelators. A model chelator, deferiprone (DFP) is covalently linked to amphiphilic poly(ethylene glycol)-polypeptide block copolymer that can assemble into micelles. The free DFP generally coordinates with iron in a ratiometric manner (3:1). However, the assembly induces DFP packing in the micelle cores, which restricts its conformational freedom. Hence DFP/iron coordination ratio in micelles is reduced (< 3:1), which leads to an enhanced chelation performance of DFP. In addition, the micellar nanocarrier usually exhibits an extended systemic circulation in contrast to the free DFP. The current work opens new avenues for developing novel nanomedicines for iron overload diseases.

摘要

我们报告了一种基于自组装的方法，用于提高小分子螯合剂的铁螯合能力。模型螯合剂，去铁酮（DFP）与两亲性聚乙二醇-多肽嵌段共聚物共价连接，可组装成胶束。游离的 DFP 通常以比例（3:1）与铁配位。然而，组装诱导 DFP 在胶束核中组装，这限制了其构象自由度。因此，胶束中的 DFP/铁配位比降低（<3:1），从而增强了 DFP 的螯合性能。此外，与游离的 DFP 相比，胶束纳米载体通常表现出延长的系统循环。目前的工作为开发用于铁过载疾病的新型纳米药物开辟了新途径。