<p>A stimulus-responsive drug delivery system holds promise for reducing adverse effects and enhancing the bioavailability of chemotherapeutic agents. In this study, amino-terminated dextran was utilized as a macromolecular initiator to prepare a range of amphiphilic dextran-b-poly(ε-benzyloxycarbonyl-<span>l</span>-lysine) (Dex-b-PZLL) copolymers with varying hydrophobic segment lengths via ring-opening polymerization (ROP). Folic acid (FA) was further grafted onto the dextran side chains via esterification (FA-Dex-b-PZLL), offering the potential tumor-specific recognition. The resulting copolymers were able to self-assemble into stable spherical micelles via dialysis and efficiently encapsulated the hydrophobic drug letrozole (LTZ). A systematic assessment was conducted on the drug encapsulation efficiency/loading capacity, drug release performance in vitro, and biocompatibility of the copolymers under aqueous conditions, indicating that these properties of the FA-Dex-b-PZLL micelles mainly depended on the copolymer composition. The optimized micelles, with a balanced hydrophilic/hydrophobic ratio, achieved a drug loading capacity with approximately 8.49% and an encapsulation efficiency with about 46.39%. Moreover, LTZ/FA-Dex-b-PZLL micelles exhibited pH-responsive release, with cumulative release rates within 72&#xa0;h of 20.74%, 27.14% and 62.96% in phosphate buffer at pH 7.4, 6.5 and 4.5, respectively, indicating the accelerated release under acidic conditions. In addition, the micelles showed good cytocompatibility according to the CCK-8 assay.</p> Graphical abstract <p></p>