Neutrophil/Leukemia‐Tropic Dual‐Drug Nanomedicine Potentiates the Treatment of Acute Myeloid Leukemia

Abstract Acute myeloid leukemia (AML) poses severe clinical challenges due to its heterogeneity and the scattered nature of therapeutic targets. Moreover, suboptimal drug delivery to the bone marrow, combined with the protective effects of the niche that shelters residual leukemia cells, frequently underlies chemotherapy failure and relapse. Here, a neutrophil/leukemia‐tropic polymersome vincristine/volasertib dual‐drug nanoformulation (NLP‐Vi/Vo) is reported to selectively bind to leukemia cells and neutrophils, and to ratiometrically release clinical chemotherapeutics and a polo‐like kinase 1 inhibitor, thereby potentiating the treatment of AML. NLP‐Vi/Vo induces synergistic anti‐AML effects by sensitizing AML to chemotherapy, and homes to bone marrow by hitchhiking on neutrophils, cooperatively depleting leukemia in both the bloodstream and bone marrow. NLP‐Vi/Vo shows excellent therapeutic efficacy in malignant murine AML and human AML xenograft models. Collectively, neutrophil/leukemia‐directing dual‐drug nanomedicines offer a promising treatment strategy for AML.