Stemmed DNA nanostructure for the selective delivery of therapeutics

Nanoscale. 2018 Apr 26;10(16):7511-7518. doi: 10.1039/c7nr08558c.

Abstract

DNA has emerged as a biocompatible biomaterial that may be considered for various applications. Here, we report tumor cell-specific aptamer-modified DNA nanostructures for the specific recognition and delivery of therapeutic chemicals to cancer cells. Protein tyrosine kinase (PTK)7-specific DNA aptamer sequences were linked to 15 consecutive guanines. The resulting aptamer-modified product, AptG15, self-assembled into a Y-shaped structure. The presence of a G-quadruplex at AptG15 was confirmed by circular dichroism and Raman spectroscopy. The utility of AptG15 as a nanocarrier of therapeutics was tested by loading the photosensitizer, methylene blue (MB), to the G-quadruplex as a model drug. The generated MB-loaded AptG15 (MB/AptG15) showed specific and enhanced uptake to CCRF-CEM cells, which overexpress PTK7, compared with Ramos cells, which lack PTK7, or CCRF-CEM cells treated with a PTK7-specific siRNA. The therapeutic activity of MB/AptG15 was tested by triggering its photodynamic effects. Upon 660 nm light irradiation, MB/AptG15 showed greater reactive oxygen species generation and anticancer activity in PTK7-overexpressing cells compared to cells treated with MB alone, those treated with AptG15, and other comparison groups. AptG15 stemmed DNA nanostructures have significant potential for the cell-type-specific delivery of therapeutics, and possibly for the molecular imaging of target cells.

MeSH terms

  • Aptamers, Nucleotide*
  • Cell Adhesion Molecules / genetics
  • Cell Line, Tumor
  • DNA / chemistry*
  • G-Quadruplexes
  • Gene Knockdown Techniques
  • Humans
  • Methylene Blue / administration & dosage
  • Nanostructures / chemistry*
  • Photochemotherapy
  • Photosensitizing Agents / administration & dosage*
  • Reactive Oxygen Species / chemistry
  • Receptor Protein-Tyrosine Kinases / genetics

Substances

  • Aptamers, Nucleotide
  • Cell Adhesion Molecules
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • DNA
  • PTK7 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Methylene Blue