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Multilayer associates based on oligonucleotides and gold nanoparticles

Abstract

The development of nanodevices for the efficient transport of therapeutic molecules is one of the most urgent problems of modern molecular medicine. Noncovalent agents for the delivery of nucleic acids (NA) including those based on gold nanoparticles (GNPs) represent an attractive alternative to covalent systems, since it is easier in this case to provide the controlled release of NA. We have demonstrated the possibility to create potentially biocompatible associates of GNPs containing alternating layers of oligonucleotides and other polymers as a promising platform for the delivery of oligonucleotides into living cells. The multilayer (five layers) coated GNPs can be assembled by the sequential treatment of gold nanoparticles with nonthiolated oligonucleotide (ON), thiolated carboxyl-polyethylene glycol (SH-PEG3000-COOH), and linear polyethyleneimine (PEI). We have developed an algorithm for the analysis of multilayer coated GNPs by gel electrophoresis, photon correlation spectroscopy, and transmission electron microscopy. The assembly of associates bearing two oligonucleotide layers and having a net positive surface charge has been described. Multilayer coated GNPs were shown not to degrade in the presence of a high concentration of the major blood protein, serum albumin.

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Abbreviations

NA:

nucleic acids

GNP:

gold nanoparticles

TEM:

Transmission electron microscopy

PCS:

Photon correlation spectroscopy

DTT:

dithiothreitol

FAM:

fluoresceinisothiocyanate

ON:

oligonucleotide

HSA:

human serum albumin

PEI:

linear polyethleneimine

SH-PEG3000-COOH:

thiol-containing carboxyl-polyethylene glycol

siRNA:

small interfering RNA

TAMRA:

tetramethylrhodamine

ξ:

surface potential

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Correspondence to I. A. Pyshnaya.

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Original Russian Text © V.V. Shashkova, A.V. Epanchintseva, P.E. Vorobjev, K.V. Razum, E.I. Ryabchikova, D.V. Pyshnyi, I.A. Pyshnaya, 2017, published in Bioorganicheskaya Khimiya, 2017, Vol. 43, No. 1, pp. 75–82.

The paper is based on the materials of the “Chemical Biology 2016” conference; Novosibirsk, Russia, July 24–29, 2016.

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Shashkova, V.V., Epanchintseva, A.V., Vorobjev, P.E. et al. Multilayer associates based on oligonucleotides and gold nanoparticles. Russ J Bioorg Chem 43, 64–70 (2017). https://doi.org/10.1134/S106816201606011X

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  • DOI: https://doi.org/10.1134/S106816201606011X

Keywords

  • gold nanoparticles
  • nucleic acids
  • adsorption
  • associates
  • layer-by-layer