Abstract
This work reports the development of a biomimetic membrane-wrapped nanoparticle (MWNP) platform for targeted chemotherapy of acute myeloid leukemia (AML). Doxorubicin (DOX), a chemotherapeutic used to treat leukemias, lymphomas, and other cancers, was encapsulated in polymeric NPs that were coated with cytoplasmic membranes derived from human AML cells. The release rate of DOX from the MWNPs was characterized under both storage and physiological conditions, with faster release observed at pH 5.5 than pH 7.4. The system was then introduced to AML cell cultures to test the functionality of the released DOX cargo as compared to DOX delivered freely or via NPs coated with poly(ethylene glycol) (PEG). The MWNPs delivered DOX in an efficient and targeted manner, inducing up to 80% apoptosis in treated cells at a dose of 5 μM, compared to 15% for free DOX and 17% for DOX-loaded PEG-coated NPs at the same drug concentration. The mechanism of cell death was confirmed as DNA double-strand breaks through a γH2A.X assay, indicating that the released DOX retained its expected mechanism of action. These findings designate MWNPs as a robust drug delivery system with great potential for future development in treatments of AML and other blood cancers.