Dual-Targeted\nDrug Delivery to Myeloid Leukemia Cells\nvia Complement- and Transferrin-Based Protein Corona

Although\ntraditionally regarded as an impediment, the\nprotein corona\ncan facilitate the advancement of targeted drug delivery systems.\nThis study presents an innovative approach for targeting acute myeloid\nleukemia (AML) using nanoparticles with agglutinated protein (NAPs).\nAgglutinated transferrin and C3b in NAPs selectively bind to CD71\nand CD11b, receptors that are overexpressed on myeloid leukemic cells\ncompared to nonmalignant cells. <i>In vitro</i>, NAPs achieved\na 73.9% doxorubicin (DOX) uptake in leukemic cells, compared to 6.19%\nfor the free drug, while significantly reducing off-target accumulation\nin normal cells from 42.9% to 5.76%. <i>In vivo</i>, the\ndistribution of NAPs correlated to the organ infiltration pattern\nof leukemic cells. NAPs demonstrated antileukemic activity in both <i>in vitro</i> and <i>in vivo</i> NSG mouse models,\ninducing cell death via apoptosis and ferroptosis. In conclusion,\nNAP-mediated targeted drug delivery represents a promising therapeutic\nstrategy for AML, enhancing treatment efficacy and minimizing off-target\neffects.