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. (C) 2018 Elsevier Inc. All rights reserved.