摘要Background:Artesunate(ASA)acts as an·O?-source through the breakdown of en-doperoxide bridges catalyzed by Fe 2+,yet its efficacy in ASA-based nanodrugs is lim-ited by poor intracellular delivery.Methods:ASA-hyaluronic acid(HA)conjugates were formed from hydrophobic ASA and hydrophilic HA by an esterification reaction first,and then self-targeting nanomi-celles(NM)were developed using the fact that the amphiphilic conjugates of ASA and HA are capable of self-assembling in aqueous environments.Results:These ASA-HA NMs utilize CD44 receptor-mediated transcytosis to greatly enhance uptake by breast cancer cells.Subsequently,endogenous Fe 2+from the tumor catalyzes the released ASA to produce highly toxic·O?-radicals to kill tumor cells,although sustained tumor growth inhibition can be achieved via in vivo experiments.Conclusions:Self-targeting NMs represent a promising strategy for enhancing ASA-based treatments,leveraging clinically approved drugs to expedite drug development and clinical research in oncology.