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Novel CD123-aptamer-originated targeted drug trains for selectively delivering cytotoxic agent to tumor cells in acute myeloid leukemia theranostics.

Drug delivery (2017-08-29)
Haibin Wu, Meng Wang, Bo Dai, Yanmin Zhang, Ying Yang, Qiao Li, Mingyue Duan, Xi Zhang, Xiaomei Wang, Anmao Li, Liyu Zhang
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 + 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 + cells and retains the efficacy of Dox, while significantly reducing drug uptake and eased toxicity to CD123- cells in vitro (p < .01). Moreover, TDT can ease Dox cytoxicity to normal tissues, prolong survivals and inhibit tumor growth of mouse xenograft tumor model in vivo. These suggest that CD123 aptamer and CD123 aptamer-mediated targeted drug delivery system may have potential applications for selective delivery cytotoxic agents to CD123-expressing tumors in AML theranostics.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
IgG from human serum, reagent grade, ≥95% (SDS-PAGE), essentially salt-free, lyophilized powder
Sigma-Aldrich
Cell Counting Kit - 8, for quantitation of viable cell number in proliferation and cytotoxicity assays