Hybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation

J Control Release. 2015 Dec 28;220(Pt B):608-16. doi: 10.1016/j.jconrel.2015.09.035. Epub 2015 Sep 21.

Abstract

This work presents a new concept in hybrid hydrogel design. Synthetic water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) polymers grafted with multiple peptide nucleic acids (PNAs) are crosslinked upon addition of the linker DNA. The self-assembly is mediated by the PNA-DNA complexation, which results in the formation of hydrophilic polymer networks. We show that the hydrogels can be produced through two different types of complexations. Type I hydrogel is formed via the PNA/DNA double-helix hybridization. Type II hydrogel utilizes a unique "P-form" oligonucleotide triple-helix that comprises two PNA sequences and one DNA. Microrheology studies confirm the respective gelation processes and disclose a higher critical gelation concentration for the type I gel when compared to the type II design. Scanning electron microscopy reveals the interconnected microporous structure of both types of hydrogels. Type I double-helix hydrogel exhibits larger pore sizes than type II triple-helix gel. The latter apparently contains denser structure and displays greater elasticity as well. The designed hybrid hydrogels have potential as novel biomaterials for pharmaceutical and biomedical applications.

Keywords: DNA; HPMA polymer; Hydrogel; P-form; Peptide nucleic acid; Self-assembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / chemistry*
  • Acrylamides / metabolism
  • DNA / chemistry*
  • DNA / metabolism
  • DNA / ultrastructure
  • Elasticity
  • Gene Transfer Techniques*
  • Hydrogels
  • Hydrophobic and Hydrophilic Interactions
  • Microscopy, Atomic Force
  • Nucleic Acid Conformation
  • Peptide Nucleic Acids / chemistry*
  • Peptide Nucleic Acids / metabolism
  • Peptide Nucleic Acids / ultrastructure
  • Porosity
  • Protein Conformation
  • Rheology

Substances

  • Acrylamides
  • Hydrogels
  • Peptide Nucleic Acids
  • DNA
  • N-(2-hydroxypropyl)methacrylamide