Drug Delivery (Jan 2017)

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

  • Haibin Wu,
  • Meng Wang,
  • Bo Dai,
  • Yanmin Zhang,
  • Ying Yang,
  • Qiao Li,
  • Mingyue Duan,
  • Xi Zhang,
  • Xiaomei Wang,
  • Anmao Li,
  • Liyu Zhang

DOI
https://doi.org/10.1080/10717544.2017.1367976
Journal volume & issue
Vol. 24, no. 1
pp. 1216 – 1229

Abstract

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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.

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