Aptamer-targeted DNA nanostructures with doxorubicin to treat protein tyrosine kinase 7-positive tumours

Cell Prolif. 2019 Jan;52(1):e12511. doi: 10.1111/cpr.12511. Epub 2018 Oct 12.

Abstract

Objectives: Aptamer sgc8c is a short DNA sequence that can target protein tyrosine kinase 7 (PTK7), which was overexpressed on many tumour cells. This study aimed to fabricate a novelty DNA nanostructure drug delivery system target on PTK7-positive cells-CCRF-CEM (human T-cell ALL).

Methods: Aptamer-modified tetrahedron DNA was synthesized through one-step thermal annealing process. The sgc8c-TDNs (s-TDNs) loading DOX complexes were applied to investigate the effect to PTK7-negative and -positive cells.

Results: When s-TDN:DOX acted on PTK7-positive and -negative cells respectively, the complexes exhibited specific toxic effect on PTK7-positive cells but not on PTK7-negative Ramos cells in vitro research.

Conclusions: In this work, we successfully constructed a PTK7-targeting aptamer-guided DNA tetrahedral nanostructure (s-TDN) as a drug delivery system via a facile one-pot synthesis method. The results showed that s-TDN:DOX exhibited enhanced cytotoxicity against PTK7-positive CCRF-CEM cells, with a minor effect against PTK7-negative Ramos cells. Hence, this functionalized TDNs drug delivery system displayed its potential application in targeting PTK7-positive tumour T-cell acute lymphoblastic leukaemia.

MeSH terms

  • Aptamers, Nucleotide / metabolism*
  • Base Sequence / genetics
  • Biological Transport / physiology
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Adhesion Molecules / genetics
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • DNA / chemistry*
  • Doxorubicin / pharmacology*
  • Drug Carriers / chemistry*
  • Humans
  • Nanostructures / chemistry*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Receptor Protein-Tyrosine Kinases / genetics

Substances

  • Aptamers, Nucleotide
  • Cell Adhesion Molecules
  • Drug Carriers
  • Doxorubicin
  • DNA
  • PTK7 protein, human
  • Receptor Protein-Tyrosine Kinases