Dual-Targeted Drug Delivery to Myeloid Leukemia Cells via Complement- and Transferrin-Based Protein Corona

Although traditionally regarded as an impediment, the protein corona can facilitate the advancement of targeted drug delivery systems. This study presents an innovative approach for targeting acute myeloid leukemia (AML) using nanoparticles with agglutinated protein (NAPs). Agglutinated transferrin and C3b in NAPs selectively bind to CD71 and CD11b, receptors that are overexpressed on myeloid leukemic cells compared to nonmalignant cells. In vitro, NAPs achieved a 73.9% doxorubicin (DOX) uptake in leukemic cells, compared to 6.19% for the free drug, while significantly reducing off-target accumulation in normal cells from 42.9% to 5.76%. In vivo, the distribution of NAPs correlated to the organ infiltration pattern of leukemic cells. NAPs demonstrated antileukemic activity in both in vitro and in vivo NSG mouse models, inducing cell death via apoptosis and ferroptosis. In conclusion, NAP-mediated targeted drug delivery represents a promising therapeutic strategy for AML, enhancing treatment efficacy and minimizing off-target effects.