Blurring the Role of Oligonucleotides: Spherical Nucleic Acids as a Drug Delivery Vehicle

J Am Chem Soc. 2016 Aug 31;138(34):10834-7. doi: 10.1021/jacs.6b07554. Epub 2016 Aug 18.

Abstract

Nucleic acids are generally regarded as the payload in gene therapy, often requiring a carrier for intracellular delivery. With the recent discovery that spherical nucleic acids enter cells rapidly, we demonstrate that nucleic acids also have the potential to act as a delivery vehicle. Herein, we report an amphiphilic DNA-paclitaxel conjugate, which forms stable micellar nanoparticles in solution. The nucleic acid component acts as both a therapeutic payload for intracellular gene regulation and the delivery vehicle for the drug component. A bioreductively activated, self-immolative disulfide linker is used to tether the drug, allowing free drug to be released upon cell uptake. We found that the DNA-paclitaxel nanostructures enter cells ∼100 times faster than free DNA, exhibit increased stability against nuclease, and show nearly identical cytotoxicity as free drug. These nanostructures allow one to access a gene target and a drug target using only the payloads themselves, bypassing the need for a cocarrier system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • DNA / chemistry*
  • Disulfides / chemistry
  • Drug Carriers / chemistry*
  • Micelles
  • Models, Molecular
  • Nanoparticles / chemistry
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry*
  • Paclitaxel / chemistry

Substances

  • Disulfides
  • Drug Carriers
  • Micelles
  • Oligonucleotides
  • DNA
  • Paclitaxel