Aptamer-displaying peptide amphiphile micelles as a cell-targeted delivery vehicle of peptide cargoes

Phys Biol. 2018 Oct 22;15(6):065006. doi: 10.1088/1478-3975/aadb68.

Abstract

Peptide amphiphile micelles (PAMs) are attractive vehicles for the delivery of a variety of therapeutic and prophylactic peptides. However, a key limitation of PAMs is their lack of preferential targeting ability. In this paper, we describe our design of a PAM system that incorporates a DNA oligonucleotide amphiphile (antitail amphiphile-AA) to form A/PAMs. A cell-targeting DNA aptamer with a 3' extension sequence (tail) complementary to the AA is annealed to the surface to form aptamer-displaying PAMs (Aptamer~A/PAMs). Aptamer~A/PAMs are small, anionic, stable nanoparticles capable of delivering a large mass percentage peptide amphiphile (PA) compared to targeting DNA components. Aptamer~A/PAMs are stable for over 4 h in the presence of biological fluids. Additionally, the aptamer retains its cell-targeting properties when annealed to the A/PAM, thus leading to enhanced delivery to a specifically-targeted B-cell leukemia cell line. This exciting modular technology can be readily used with a library of different targeting aptamers and PAs, capable of improving the bioavailability and potency of the peptide cargo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aptamers, Nucleotide / chemistry*
  • Cell Line, Tumor
  • Drug Delivery Systems*
  • Humans
  • Mice
  • Micelles*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Peptides / chemistry*
  • Peptides / pharmacology*

Substances

  • Aptamers, Nucleotide
  • Micelles
  • Peptides