Novel cd123-aptamer-originated targeted drug trains for selectively delivering cytotoxic agent to tumor cells in acute myeloid leukemia theranostics

Abstract

Since conventional chemotherapy for acute myeloid leukemia (AML) has its limitations, a theranostic platform with targeted and efficient drug transport is in demand. In this study, we developed the first CD123 (AML tumor marker) aptamers and designed a novel CD123-aptamer-mediated targeted drug train (TDT) with effective, economical, biocompatible and high drug-loading capacity. These two CD123 aptamers (termed as ZW25 and CY30, respectively) can bind to a CD123 peptide epitope and CD123 þ AML cells with high specificities and KD of 29.41 nM and 15.38 nM, respectively, while has minimal cross reactivities to albumin, IgG and trypsin. Further, TDT is self-assembled from two short primers by ligand-modified ZW25 that acted as initiation position for elongation, while intercalated by doxorubicin (Dox). TDT is capable of transporting high capacity of Dox to CD123 þ cells and retains the efficacy of Dox, while significantly reducing drug uptake and eased toxicity to CD123 cells in vitro (p