BACKGROUND: Artesunate (ASA) acts as an •O₂ METHODS: ASA-hyaluronic acid (HA) conjugates were formed from hydrophobic ASA and hydrophilic HA by an esterification reaction first, and then self-targeting nanomicelles (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 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.