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 + 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.

Keywords:

• CD123 aptamer
• targeted drug train
• self-assembly
• in vivo
• high drug loading

Acknowledgments

The authors thank Dr. Dan Xu and Dr. Xiaoyun Lu in School of Life Science and Technology, Xi’an Jiaotong University for for providing us human acute myelocytic leukemia (Molm-13) and human B cell precursor leukemia (RCH-ACV) cell lines. We also thank Shaanxi Jiuzhou Medical Technology Company for their help and assistance about H&E staining during the major revision.

Disclosure statement

The authors declare no conflicts of interests.

Additional information

Funding

This work was funded by National Natural Science Foundation of China (81600993); Xi’an Science and Technology program SF1510(4).